Medicina

13 pages, 1285 KB

Open AccessEditor’s ChoiceArticle

Temporal Trends of Dengue Surveillance in Sardinia, Italy: Implications of Climate Change on Human and Entomological Monitoring

by Giovanna Deiana, Isabella Figoni, Antonella Arghittu, Guglielmo Campus, Giuseppe Satta, Cipriano Foxi, Andrea Piana, Paolo Castiglia and Marco Dettori

Medicina 2025, 61(11), 2024; https://doi.org/10.3390/medicina61112024 - 12 Nov 2025

Cited by 1 | Viewed by 1153

Abstract

Background and Objectives: Climate change is modifying the ecological and climatic conditions that influence the distribution and activity of arthropod vectors. Rising temperatures and prolonged warm seasons have favored the establishment of Aedes albopictus in Mediterranean regions, increasing the risk of autochthonous Dengue [...] Read more.

Background and Objectives: Climate change is modifying the ecological and climatic conditions that influence the distribution and activity of arthropod vectors. Rising temperatures and prolonged warm seasons have favored the establishment of Aedes albopictus in Mediterranean regions, increasing the risk of autochthonous Dengue transmission. Therefore, this study describes the evolution of Dengue surveillance in Sardinia between 2018 and 2024, integrating human and entomological data to assess trends, system performance, and implications for prevention and control. Materials and Methods: Data on human cases were retrieved from national notification systems (namely PREMAL, arbo.iss.it) and the New Health Information System. Entomological surveillance data were obtained from the Experimental Zooprophylactic Institute of Sardinia. Mosquitoes were collected using BG-Sentinel^® traps and ovitraps, covering major cities and points of entry. Descriptive analyses were conducted for both datasets. Results: Sixteen Dengue cases were reported during the study period, all imported and laboratory-confirmed in 81% of cases. Most patients were adults (mean age 38 years), and 77% required hospitalization. The most frequent travel origins were Southeast Asia, Africa, and Latin America. No autochthonous cases were identified. Entomological surveillance showed a progressive increase in Aedes albopictus captures from 2020 onwards, with seasonal peaks between September and October. Despite intensified sampling and expanded geographic coverage, no mosquito pools tested positive for the Dengue virus. Conclusions: Although no locally acquired Dengue infections have been detected, the widespread and increasing presence of Aedes albopictus indicates that Sardinia meets the ecological prerequisites for possible autochthonous transmission. Strengthening the timeliness and completeness of human surveillance, improving clinicians’ awareness of reporting requirements, promoting vaccination for travelers, and maintaining continuous entomological monitoring are essential to prevent and promptly manage future outbreaks. Full article

(This article belongs to the Special Issue Emerging Trends in Infectious Disease Prevention and Control)

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13 pages, 354 KB

Open AccessEditor’s ChoiceSystematic Review

Applications of Artificial Intelligence in Alpha-1 Antitrypsin Deficiency: A Systematic Review from a Respiratory Medicine Perspective

by Manuel Casal-Guisande, Laura Villar-Aguilar, Alberto Fernández-Villar, Esmeralda García-Rodríguez, Ana Casal and María Torres-Durán

Medicina 2025, 61(10), 1768; https://doi.org/10.3390/medicina61101768 - 30 Sep 2025

Cited by 2 | Viewed by 1224

Abstract

Background and Objectives: Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition associated with chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and emphysema, and with liver involvement through a distinct toxic gain-of-function mechanism. Despite its clinical relevance, AATD remains [...] Read more.

Background and Objectives: Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition associated with chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and emphysema, and with liver involvement through a distinct toxic gain-of-function mechanism. Despite its clinical relevance, AATD remains underdiagnosed and exhibits marked phenotypic heterogeneity. Artificial intelligence (AI) has shown growing potential in respiratory medicine, yet its application to AATD is still limited. This systematic review synthesizes the clinical evidence on AI in AATD, primarily in the respiratory domain and, where available, in hepatic outcomes. Materials and Methods: We conducted a PRISMA-guided search (PubMed, Web of Science, IEEE Xplore) for original, peer-reviewed articles (January 2014–September 2025) applying AI to detection, classification, stratification, or prediction tasks in AATD. Results: Six studies met eligibility criteria. Supervised models (e.g., XGBoost, penalized regression, Transformer-based architectures) and one unsupervised approach were identified. Applications included screening in COPD populations, prediction of emphysema progression from CT, proteomic modeling of lung function, identification of clinical subgroups, and prediction of clinical outcomes in AATD-associated liver disease. External validation and genotype diversity remained limited across studies. Conclusions: Although AI shows promise in improving detection, prognosis, and patient stratification in AATD across both respiratory and hepatic manifestations, the current evidence remains limited. Broader, multicenter validation in genotype-diverse cohorts is required to confirm its clinical utility and support the implementation of precision medicine in AATD. Full article

(This article belongs to the Section Pulmonology)

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16 pages, 5095 KB

Open AccessEditor’s ChoiceArticle

Nationwide Epidemiology of Hospitalized Acute ACL Ruptures in Romania: A 7-Year Analysis (2017–2023)

by Gloria Alexandra Tolan, Ionut Daniel Raducan, Bogdan Uivaraseanu, Delia Mirela Tit, Gabriela S. Bungau, Andrei-Flavius Radu and Cristian George Furau

Medicina 2025, 61(9), 1672; https://doi.org/10.3390/medicina61091672 - 15 Sep 2025

Cited by 3 | Viewed by 1355

Abstract

Background and Objectives: Anterior cruciate ligament (ACL) rupture is one of the most frequent and debilitating knee injuries, especially among young, physically active individuals. While extensively studied in Western countries, large-scale epidemiological data from Eastern Europe remain scarce. This study offers the first [...] Read more.

Background and Objectives: Anterior cruciate ligament (ACL) rupture is one of the most frequent and debilitating knee injuries, especially among young, physically active individuals. While extensively studied in Western countries, large-scale epidemiological data from Eastern Europe remain scarce. This study offers the first nationwide assessment of hospitalization-based incidence of acute ACL rupture in Romania. Materials and Methods: We conducted a retrospective analysis of all hospital discharges coded as S83.53 (ACL rupture) between 2017 and 2023, using national public health datasets. Incidence rates were calculated per 100,000 inhabitants based on the 2021 national census. Data were analyzed by sex, age, year, and region. Results: A total of 4332 ACL-related discharges were recorded (3130 males and 1202 females), yielding an average incidence of 3.23 per 100,000 per year. Incidence in males was consistently higher (up to 5.63) than in females (up to 2.10). The peak incidence occurred in 2023, while the lowest was observed in 2020, likely due to COVID-19-related restrictions. Linear regression showed a significant upward trend over time (R² = 0.966, p < 0.001). The highest age-specific incidence was found in males aged 25–29 years (116.3/100,000) and in females aged 15–19 years (35.4/100,000). Cases were rare above the age of 50. Geographically, incidence varied widely, with Bucharest, Timiș, and Bihor recorded the highest rates, while several other counties reported near-zero values. Conclusions: This study provides the first nationwide analysis of hospitalization-based ACL rupture incidence in Romania, revealing marked differences by age, sex, and region. While the findings reflect only acute cases requiring inpatient care, they underscore the need for more comprehensive injury surveillance, improved access to orthopedic services, and targeted prevention strategies tailored to high-risk populations. Full article

(This article belongs to the Special Issue Anterior Cruciate Ligament (ACL) Injury)

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19 pages, 495 KB

Open AccessEditor’s ChoiceReview

Redefining Breast Cancer Care by Harnessing Computational Drug Repositioning

by Elena-Daniela Jurj, Daiana Colibășanu, Sabina-Oana Vasii, Liana Suciu, Cristina Adriana Dehelean and Lucreția Udrescu

Medicina 2025, 61(9), 1640; https://doi.org/10.3390/medicina61091640 - 10 Sep 2025

Cited by 4 | Viewed by 1984

Abstract

Breast cancer faces significant therapeutic challenges, particularly for triple-negative breast cancer (TNBC), due to limited targeted therapies and drug resistance. Drug repositioning leverages existing safety and pharmacokinetic data to expedite the identification of new indications with cost-effective benefits compared to de novo drug [...] Read more.

Breast cancer faces significant therapeutic challenges, particularly for triple-negative breast cancer (TNBC), due to limited targeted therapies and drug resistance. Drug repositioning leverages existing safety and pharmacokinetic data to expedite the identification of new indications with cost-effective benefits compared to de novo drug discovery. In this critical narrative review, we examine recent advances in computational repositioning strategies for breast cancer, focusing on network-based methods, computer-aided drug design, artificial intelligence and machine learning, transcriptomic signature matching, and multi-omics integration. We highlight key case studies that have progressed to preclinical validation or clinical evaluation. We assess comparative performance metrics, experimental validation outcomes, and real-world success rates. We also present critical methodological challenges, including data heterogeneity, bias in real-world data, and the need for study reproducibility. Our review emphasizes the importance of window-of-opportunity trials and the need for standardized data sharing and reproducible pipelines. These insights highlight the groundbreaking potential of in silico repositioning in addressing unmet needs in breast cancer therapy. Full article

(This article belongs to the Special Issue New Developments in Diagnosis and Management of Breast Cancer)

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20 pages, 382 KB

Open AccessEditor’s ChoiceArticle

Association Between Redox and Inflammatory Biomarkers with the Presence and Severity of Obstructive Sleep Apnea

by Ana Ninić, Branislava Rajkov, Jelena Kotur-Stevuljević, Sanja Erceg, Miron Sopić, Jelena Munjas, Vesna Spasojević-Kalimanovska, Marija Mitrović, Lidija Memon, Vera Gardijan, Milica Brajković, Slobodan Klašnja and Marija Zdravković

Medicina 2025, 61(9), 1557; https://doi.org/10.3390/medicina61091557 - 29 Aug 2025

Cited by 2 | Viewed by 1305

Abstract

Background and Objectives: Obstructive sleep apnea (OSA) represents an increasing public health concern, closely linked with cardiovascular, metabolic, and neurocognitive disorders, as well as impaired quality of life. The complex pathophysiology of OSA involves upper airway dysfunction, oxidative stress, and inflammation, with endothelial [...] Read more.

Background and Objectives: Obstructive sleep apnea (OSA) represents an increasing public health concern, closely linked with cardiovascular, metabolic, and neurocognitive disorders, as well as impaired quality of life. The complex pathophysiology of OSA involves upper airway dysfunction, oxidative stress, and inflammation, with endothelial dysfunction considered central to its associated comorbidities. Despite notable advances in OSA research, the biological mechanisms driving these complications remain insufficiently understood. The present study aimed to examine the associations between redox status, proinflammatory biomarkers, and the gene expression of full-length receptor for advanced glycation end products (flRAGE) and transforming growth factor beta 1 (TGF-β1) in relation to the presence and severity of OSA. Materials and Methods: The study cohort comprised 125 participants with diagnosed OSA and 42 controls without evidence of OSA. General and clinical characteristics were recorded for all participants. Laboratory analyses included the assessment of redox and inflammatory markers in serum and plasma, while flRAGE and TGF-β1 messenger ribonucleic acids (mRNA) were quantified in peripheral blood mononuclear cells. Results: Patients with OSA demonstrated elevated oxidative stress and inflammation, characterized by increased total antioxidant status (TAS) and C-reactive protein CRP levels, together with reduced concentrations of soluble RAGE (sRAGE). The severity of OSA, indicated by the apnea-hypopnea index, increases total oxidative status (TOS) and TGF-β1 mRNA, while sRAGE decreases. The sRAGE–ROS-related factor was negatively associated with OSA, whereas the redox status factor showed a positive association. TOS was independently and positively correlated with OSA severity. Conclusions: Individuals with OSA exhibit a state of enhanced oxidative stress and inflammation. Increasing severity of OSA was associated with rising TOS and TGF-β1 mRNA expression, accompanied by declining sRAGE concentrations. A combined redox–inflammatory biomarker profile was found to be associated with both the presence and severity of OSA. Full article

(This article belongs to the Section Pulmonology)

22 pages, 1072 KB

Open AccessEditor’s ChoiceSystematic Review

Using Computerised Gait Analysis to Assess Changes After Rehabilitation in Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Gait Speed Improvement

by Mihaela Minea, Sermina Ismail, Lucian Cristian Petcu, Andreea-Dalila Nedelcu, Adina Petcu, Alexandra-Elena Minea and Mădălina-Gabriela Iliescu

Medicina 2025, 61(9), 1540; https://doi.org/10.3390/medicina61091540 - 27 Aug 2025

Cited by 3 | Viewed by 5012

Abstract

Background and objectives: Knee osteoarthritis (KOA) is a degenerative joint disorder often associated with altered gait mechanics. This systematic review aims to evaluate the effect of rehabilitation treatment on walking, with a focus on gait speed. Material and methods: A systematic [...] Read more.

Background and objectives: Knee osteoarthritis (KOA) is a degenerative joint disorder often associated with altered gait mechanics. This systematic review aims to evaluate the effect of rehabilitation treatment on walking, with a focus on gait speed. Material and methods: A systematic search was conducted in PubMed, Scopus, Web of Science, Cochrane, and PEDro databases, following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. Randomised controlled trials published in English between 2015 and 2025, involving patients with KOA undergoing rehabilitation and using computerised gait measurements, including 3D motion capture, force plates, and instrumented treadmills, were included. A meta-analysis was conducted on the selected studies assessing gait speed, with the risk of bias being evaluated using the Cochrane Risk of Bias 2 tool for RCTs. Results: Out of 2143 articles, 7 studies met the inclusion criteria. These studies showed increased gait speed in patients with KOA following exercise therapy, various walking training programmes, massage, or dietary interventions. The meta-analysis revealed a standardised mean difference (SMD) of 1.807, with a 95% confidence interval (CI) of [1.637, 1.977] (p < 0.001). The interventions were associated with improvements in walking parameters and quality of life, as well as reductions in pain and fall risk. Substantial heterogeneity was noted, likely due to variations in intervention types and study populations. Conclusions: The results suggest an overall improvement in gait speed in the intervention groups compared to the control groups. However, only a limited number of studies have investigated the effects of physiotherapy, bath therapy, or mud therapy on gait mechanics in patients with KOA. Full article

(This article belongs to the Special Issue Advances in Pathogenesis, Rehabilitation, and Treatment of Knee Osteoarthritis)

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15 pages, 392 KB

Open AccessEditor’s ChoiceArticle

Systemic Immune-Inflammation Index and Related Hematologic Markers as Prognostic Tools in Type 2 Diabetes

by Raluca Cosma-Lăzuran, Daniel-Corneliu Leucuta and Mihaela-Simona Popoviciu

Medicina 2025, 61(8), 1433; https://doi.org/10.3390/medicina61081433 - 9 Aug 2025

Cited by 9 | Viewed by 2872

Abstract

Background and Objectives: Chronic low-grade inflammation plays a key role in the pathogenesis of type 2 diabetes mellitus (T2DM) and its vascular complications. Hematological indices derived from routine blood counts, such as neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte [...] Read more.

Background and Objectives: Chronic low-grade inflammation plays a key role in the pathogenesis of type 2 diabetes mellitus (T2DM) and its vascular complications. Hematological indices derived from routine blood counts, such as neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), have been proposed as surrogate markers for systemic inflammation and predictors of cardiovascular risk. This study aimed to evaluate the predictive value of these inflammatory indices concerning the presence of micro- and macrovascular complications and cardiovascular mortality in patients with type 2 diabetes mellitus. Materials and Methods: We conducted a retrospective cohort study including 237 patients with T2DM. We assessed the association between hematological indices and cardiovascular mortality, followed by a ROC curve analysis to evaluate their predictive performance, and a multiple logistic regression. Results: Thirty patients (12.66%) died during the study period. ROC analysis showed that SIRI (AUC = 0.680 [95% CI 0.576–0.779]), LMR (AUC = 0.667 [95% CI 0.564–0.763]), AISI (AUC = 0.662 [95% CI 0.553–0.768]), and NLR (AUC = 0.657 [95% CI 0.545–0.764]) had the best discriminative capacity, all with specificity >70%. The relation remained significant even after adjustments for confounding variables in multiple logistic regression. For microvascular complications, Monocyte count (AUC = 0.611 [95% CI 0.532–0.69]) and LMR (AUC = 0.608 [95% CI 0.521–0.695]) showed minimal but notable predictive value. Conclusions: SIRI, LMR, AISI, and NLR were significantly associated with mortality and demonstrated modest discriminative ability. These markers, accessible and cost-effective, may be useful tools for risk stratification in T2DM patients. Further validation in prospective cohorts is warranted. Full article

(This article belongs to the Section Endocrinology)

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17 pages, 1157 KB

Open AccessEditor’s ChoiceReview

Multidisciplinary Postoperative Ileus Management: A Narrative Review

by Sun Yu, Katrina Kerolus, Zhaosheng Jin, Sandi Bajrami, Paula Denoya and Sergio D. Bergese

Medicina 2025, 61(8), 1344; https://doi.org/10.3390/medicina61081344 - 25 Jul 2025

Cited by 9 | Viewed by 8084

Abstract

Postoperative ileus is a prolonged impairment of gastrointestinal motility following surgical procedures. This often leads to increased morbidity, extended hospital stays, and high healthcare expenditures. In this review, we discuss the pathophysiology underlying postoperative ileus, its epidemiology, and perioperative management strategies. Patient characteristics, [...] Read more.

Postoperative ileus is a prolonged impairment of gastrointestinal motility following surgical procedures. This often leads to increased morbidity, extended hospital stays, and high healthcare expenditures. In this review, we discuss the pathophysiology underlying postoperative ileus, its epidemiology, and perioperative management strategies. Patient characteristics, as well as expected perioperative course, could be used to stratify the risks of postoperative ileus. Preventive measures hinge upon a multimodal approach, minimally invasive surgical techniques, fluid management, early postoperative ambulation, and opioid-sparing analgesia strategies. Adjuvant interventions such as alvimopan, caffeine, and chewing gum have demonstrated efficacy in modulating the neurogenic and inflammatory components of postoperative ileus. Minimally invasive approaches, comprehensive perioperative management, and adjuvant therapies hold promise for prevention. Current management relies heavily on supportive care, underscoring the need for research into the underlying neurogenic and inflammatory mechanisms to guide the development of targeted treatments. Full article

(This article belongs to the Section Surgery)

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12 pages, 1018 KB

Open AccessEditor’s ChoiceSystematic Review

Efficacy and Safety of Radioligand Therapy with Actinium-225 DOTATATE in Patients with Advanced, Metastatic or Inoperable Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis

by Alessio Rizzo, Alessio Imperiale, Salvatore Annunziata, Roberto C. Delgado Bolton, Domenico Albano, Francesco Fiz, Arnoldo Piccardo, Marco Cuzzocrea, Gaetano Paone and Giorgio Treglia

Medicina 2025, 61(8), 1341; https://doi.org/10.3390/medicina61081341 - 24 Jul 2025

Cited by 3 | Viewed by 2856

Abstract

Background and Objectives: Peptide receptor radionuclide therapy (PRRT) using radiopharmaceuticals labelled with Lutetium-177 is currently a therapeutic option for patients with advanced neuroendocrine neoplasms overexpressing somatostatin receptors (SSTRs). One promising option that has gained interest for PRRT is using alpha-emitting radioisotopes such [...] Read more.

Background and Objectives: Peptide receptor radionuclide therapy (PRRT) using radiopharmaceuticals labelled with Lutetium-177 is currently a therapeutic option for patients with advanced neuroendocrine neoplasms overexpressing somatostatin receptors (SSTRs). One promising option that has gained interest for PRRT is using alpha-emitting radioisotopes such as Actinium-225. The aim of this study was to perform a systematic review and meta-analysis on the efficacy and safety of radioligand therapy with Actinium-225 DOTATATE in advanced, metastatic or inoperable neuroendocrine neoplasms. Materials and Methods: A comprehensive literature search of studies on radioligand therapy with Actinium-225 DOTATATE in neuroendocrine neoplasms was carried out. Three different bibliographic databases (Cochrane Library, Embase, and PubMed/MEDLINE) were screened up to May 2025. Eligible articles were selected, relevant data were extracted, and the main findings on efficacy and safety are summarized through a systematic review. Furthermore, proportional meta-analyses on the disease response rate and disease control rate were performed. Results: Five studies (153 patients) published from 2020 were included in the systematic review. The pooled disease response rate and disease control rate of radioligand therapy using Actinium-225 DOTATATE were 51.6% and 88%, respectively. This treatment was well-tolerated in most patients with advanced, metastatic or inoperable neuroendocrine neoplasms. Conclusions: Radioligand therapy with Actinium-225 DOTATATE in advanced, metastatic or inoperable neuroendocrine neoplasms is effective with an acceptable toxicity profile and potential advantages compared with SSTR-ligands labelled with Lutetium-177. Currently, the number of published studies on this treatment is still limited, and results from multicenter randomized controlled trials are needed to translate this therapeutic option into clinical practice. Full article

(This article belongs to the Special Issue Clinical Treatment of Neuroendocrine Neoplasm)

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24 pages, 743 KB

Open AccessEditor’s ChoiceReview

Surgical Treatment, Rehabilitative Approaches and Functioning Assessment for Patients Affected by Breast Cancer-Related Lymphedema: A Comprehensive Review

by Paola Ciamarra, Alessandro de Sire, Dicle Aksoyler, Giovanni Paolino, Carmen Cantisani, Francesco Sabbatino, Luigi Schiavo, Renato Cuocolo, Carlo Pietro Campobasso and Luigi Losco

Medicina 2025, 61(8), 1327; https://doi.org/10.3390/medicina61081327 - 23 Jul 2025

Cited by 3 | Viewed by 4604

Abstract

Introduction: Breast cancer therapy is a common cause of lymphedema. The accumulation of protein-rich fluid in the affected extremity leads to a progressive path—swelling, inflammation, and fibrosis—namely, irreversible changes. Methods: A scientific literature analysis was performed on PubMed/Medline, Scopus, Web of Science (WoS), [...] Read more.

Introduction: Breast cancer therapy is a common cause of lymphedema. The accumulation of protein-rich fluid in the affected extremity leads to a progressive path—swelling, inflammation, and fibrosis—namely, irreversible changes. Methods: A scientific literature analysis was performed on PubMed/Medline, Scopus, Web of Science (WoS), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Physiotherapy Evidence Database (PEDro) from inception until 30 June 2024. Results: Breast cancer-related lymphedema (BCRL) is indeed an important healthcare burden both due to the significant patient-related outcomes and the overall social impact of this condition. Even though lymphedema is not life-threatening, the literature underlined harmful consequences in terms of pain, infections, distress, and functional impairment with a subsequent and relevant decrease in quality of life. Currently, since there is no cure, the therapeutic approach to BCRL aims to slow disease progression and prevent related complications. A comprehensive overview of postmastectomy lymphedema is offered. First, the pathophysiology and risk factors associated with BCRL were detailed; then, diagnosis modalities were depicted highlighting the importance of early detection. According to non-negligible changes in patients’ everyday lives, novel criteria for patients’ functioning assessment are reported. Regarding the treatment modalities, a wide array of conservative and surgical methods both physiologic and ablative were analyzed with their own outcomes and downsides. Conclusions: Combined strategies and multidisciplinary protocols for BCRL, including specialized management by reconstructive surgeons and physiatrists, along with healthy lifestyle programs and personalized nutritional counseling, should be compulsory to address patients’ demands and optimize the treatment of this harmful and non-curable condition. The Lymphedema-specific ICF Core Sets should be included more often in the overall outcome evaluation with the aim of obtaining a comprehensive appraisal of the treatment strategies that take into account the patient’s subjective score. Full article

(This article belongs to the Section Surgery)

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20 pages, 552 KB

Open AccessEditor’s ChoiceReview

Sarcopenia in Urothelial Bladder Carcinoma: A Narrative Review

by Constantin Radu Vrabie, Andreea Ioana Parosanu and Cornelia Nitipir

Medicina 2025, 61(7), 1307; https://doi.org/10.3390/medicina61071307 - 20 Jul 2025

Cited by 3 | Viewed by 1465

Abstract

Background and Objectives: Urothelial bladder carcinoma includes a spectrum of malignant lesions with heterogeneous molecular, biological, and clinical features and a variable risk of progression from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive disease (MIBC) and ultimately to metastatic urothelial carcinoma (mUC). Sarcopenia, [...] Read more.

Background and Objectives: Urothelial bladder carcinoma includes a spectrum of malignant lesions with heterogeneous molecular, biological, and clinical features and a variable risk of progression from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive disease (MIBC) and ultimately to metastatic urothelial carcinoma (mUC). Sarcopenia, a condition secondary to a catabolic state, is characterized by progressive loss of skeletal muscle mass and function and is highly prevalent across all stages of bladder cancer. This review aims to synthesize current evidence regarding the clinical impact of sarcopenia and its dynamic changes throughout the disease course. Materials and Methods: A narrative literature review was conducted using PubMed, Scopus, and Cochrane databases, incorporating the most relevant published sources. Search terms included “bladder carcinoma”, “sarcopenia”, “body composition”, “NMIBC”, and “MIBC”. Case reports and congress abstracts were excluded. Results: In NMIBC treated with intravesical Bacillus Calmette–Guérin (BCG), sarcopenia has been shown to have a negative predictive value in some studies. Among patients receiving neoadjuvant chemotherapy (NAC) for MIBC, sarcopenia has been associated with increased toxicity, dose reductions, and treatment delays. In the context of radical surgery, sarcopenia correlates with increased postoperative mortality and a higher rate of severe complications. In mUC, low muscle mass is a negative prognostic factor regardless of treatment type and is associated with chemotherapy-related hematologic toxicity, although it does not appear to predict immune-related adverse events (irAEs). Conclusions: Sarcopenia is a highly prevalent and clinically relevant phenotype of urothelial bladder cancer patients, impacting prognosis, treatment response, and chemotherapy toxicity. Incorporating sarcopenia with other relevant components of body composition (BC) and systemic inflammatory markers may facilitate the development of more robust risk scores. Current evidence is primarily limited by the retrospective design of most studies. Future prospective research is needed to clarify the prognostic role of sarcopenia and support its integration into routine clinical decision-making. Full article

(This article belongs to the Section Oncology)

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14 pages, 8916 KB

Open AccessEditor’s ChoiceReview

Dens Invaginatus: A Comprehensive Review of Classification and Clinical Approaches

by Abayomi O. Baruwa, Craig Anderson, Adam Monroe, Flávia Cracel Nogueira, Luís Corte-Real and Jorge N. R. Martins

Medicina 2025, 61(7), 1281; https://doi.org/10.3390/medicina61071281 - 16 Jul 2025

Cited by 2 | Viewed by 5115

Abstract

Dens invaginatus is a developmental dental anomaly characterized by the infolding of the enamel organ into the dental papilla during early odontogenesis. This process leads to a broad spectrum of anatomical variations, ranging from minor enamel-lined pits confined to the crown to deep [...] Read more.

Dens invaginatus is a developmental dental anomaly characterized by the infolding of the enamel organ into the dental papilla during early odontogenesis. This process leads to a broad spectrum of anatomical variations, ranging from minor enamel-lined pits confined to the crown to deep invaginations extending through the root, occasionally communicating with periodontal or periapical tissues. The internal complexity of affected teeth presents diagnostic and therapeutic challenges, particularly in severe forms that mimic root canal systems or are associated with pulpal or periapical pathology. Maxillary lateral incisors are most frequently affected, likely due to their unique developmental timeline and morphological susceptibility. Although various classification systems have been proposed, Oehlers’ classification remains the most clinically relevant due to its simplicity and correlation with treatment complexity. Recent advances in diagnostic imaging, especially cone beam computed tomography (CBCT), have revolutionized the identification and classification of these anomalies. CBCT-based adaptations of Oehlers’ classification allow for the precise assessment of invagination extent and pulpal involvement, facilitating improved treatment planning. Contemporary therapeutic strategies now include calcium-silicate-based cement sealing materials, endodontic microsurgery for inaccessible anatomy, and regenerative endodontic procedures for immature teeth with necrotic pulps. Emerging developments in artificial intelligence, genetic research, and tissue engineering promise to further refine diagnostic capabilities and treatment options. Early detection remains critical to prevent complications such as pulpal necrosis or apical disease. A multidisciplinary, image-guided, and patient-centered approach is essential for optimizing clinical outcomes in cases of dens invaginatus. Full article

(This article belongs to the Special Issue Medicine and Dentistry: New Methods and Clinical Approaches—2nd Edition)

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22 pages, 1269 KB

Open AccessEditor’s ChoiceArticle

Pre- and Post- COVID-19 Pandemic Pneumonia Rates in Hospitalized Schizophrenia Patients

by Ana-Aliana Miron, Petru Iulian Ifteni, Alexandra-Elena Lungu, Elena-Luiza Dragomirescu, Lorena Dima and Andreea Teodorescu

Medicina 2025, 61(7), 1251; https://doi.org/10.3390/medicina61071251 - 10 Jul 2025

Cited by 3 | Viewed by 1755

Abstract

Background and Objectives: Schizophrenia is a disabling psychiatric condition, affecting around 1% of people worldwide. It has been ranked among the ten most disabling conditions globally. Alongside the psychological and social burdens imposed on individuals suffering from this disease, there are also [...] Read more.

Background and Objectives: Schizophrenia is a disabling psychiatric condition, affecting around 1% of people worldwide. It has been ranked among the ten most disabling conditions globally. Alongside the psychological and social burdens imposed on individuals suffering from this disease, there are also serious complications regarding the physical health of these patients. Pneumonia is a significant cause of death in patients with schizophrenia. This group of patients also has a higher risk of developing pneumonia and all-cause mortality compared to those without schizophrenia, along with an increased overall mortality rate. A retrospective study revealed that advanced age, underweight, smoking, and the use of high-dose atypical antipsychotics increase the risk of pneumonia-related mortality in hospitalized patients. Our study aims to examine differences in factors associated with pneumonia in hospitalized patients with schizophrenia, before and after the COVID-19 pandemic, as well as to identify potential changes in clinical characteristics and outcomes. Materials and Methods: This is an observational, retrospective analysis, based on the review of medical records of psychiatric inpatients diagnosed with schizophrenia according to the DSM-5 criteria. Patients were selected according to the following criteria: both schizophrenia and pneumonia diagnoses, hospitalized in Spitalul Clinic de Psihiatrie si Neurologie Brasov during 1 March 2018–1 March 2020, and 1 March 2022–1 March 2024, respectively. Results: A total of 27 patients met the inclusion criteria; 13 patients (48%) were in the pre-pandemic group and 14 patients (52%) in the post-pandemic group. Contrary to other reports, our results showed relatively low pneumonia rates in hospitalized schizophrenia patients (1.02% pre-pandemic and 1.63% post-pandemic), and rates were higher in female patients (61.54% pre-pandemic and 71.43% post-pandemic). Post-pandemic, most cases (42.86%) were registered during summer, in a schizophrenia population with mostly urban residence and with lower smoking rates than the pre-pandemic group. Physical restraints were, however, more frequently utilized in the post-pandemic group. Conclusions: Pneumonia risk factors might register a change in the post-pandemic years. Polypharmacy and physical restraints are probably underestimated risk factors for pneumonia in schizophrenia patients, while a multidisciplinary approach and preventive measures might exert a protective role. Full article

(This article belongs to the Special Issue Mental Health Care: Pandemic and Beyond)

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13 pages, 840 KB

Open AccessEditor’s ChoiceArticle

Full-Blood Inflammatory Ratios Predict Length of Stay but Not Early Death in Romanian Pulmonary Tuberculosis

by Ionut-Valentin Stanciu, Ariadna-Petronela Fildan, Barkha Rani Thakur, Adrian Cosmin Ilie, Livia Stanga, Cristian Oancea, Emanuela Tudorache, Felix Bratosin, Ovidiu Rosca, Iulia Bogdan, Anca Chisoi, Ionela Preotesoiu, Viorica Zamfir and Elena Dantes

Medicina 2025, 61(7), 1238; https://doi.org/10.3390/medicina61071238 - 9 Jul 2025

Cited by 11 | Viewed by 1220

Abstract

Background and Objectives: Blood-borne inflammatory ratios have been proposed as inexpensive prognostic tools across a range of diseases, but their role in pulmonary tuberculosis (TB) remains uncertain. In this retrospective case–control analysis, we explored whether composite indices derived from routine haematology—namely the [...] Read more.

Background and Objectives: Blood-borne inflammatory ratios have been proposed as inexpensive prognostic tools across a range of diseases, but their role in pulmonary tuberculosis (TB) remains uncertain. In this retrospective case–control analysis, we explored whether composite indices derived from routine haematology—namely the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic immune–inflammation index (SII) and a novel CRP–Fibrinogen Index (CFI)—could enhance risk stratification beyond established cytokine measurements among Romanian adults with culture-confirmed pulmonary T. Materials and Methods: Data were drawn from 80 consecutive TB in-patients and 50 community controls. Full blood counts, C-reactive protein, fibrinogen, and four multiplex cytokines were extracted from electronic records, and composite indices were calculated according to standard formulas. The primary outcomes were in-hospital mortality within 90 days and length of stay (LOS). Results: Among TB patients, the median NLR was 3.70 (IQR 2.54–6.14), PLR was 200 (140–277) and SII was 1.36 × 10⁶ µL⁻¹ (0.74–2.34 × 10⁶), compared with 1.8 (1.4–2.3), 117 (95–140) and 0.46 × 10⁶ µL⁻¹ (0.30–0.60 × 10⁶) in controls. Those with SII above the cohort median exhibited more pronounced acute-phase responses (median CRP 96 vs. 12 mg L⁻¹; fibrinogen 578 vs. 458 mg dL⁻¹), yet median LOS remained virtually identical (29 vs. 28 days) and early mortality was low in both groups (8% vs. 2%). The CFI showed no clear gradient in hospital stay across its quartiles, and composite ratios—while tightly inter-correlated—demonstrated only minimal association with cytokine levels and LOS. Conclusions: Composite cell-count indices were markedly elevated but did not predict early death or prolonged admission. In low-event European cohorts, their chief value may lie in serving as cost-free gatekeepers, flagging those who should proceed to more advanced cytokine or genomic testing. Although routine reporting of NLR and SII may support low-cost surveillance, validation in larger, multicentre cohorts with serial sampling is needed before these indices can be integrated into clinical decision-making. Full article

(This article belongs to the Section Pulmonology)

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17 pages, 451 KB

Open AccessEditor’s ChoiceReview

Biomarkers and Neuropsychological Tools in Attention-Deficit/Hyperactivity Disorder: From Subjectivity to Precision Diagnosis

by Ion Andrei Hurjui, Ruxandra Maria Hurjui, Loredana Liliana Hurjui, Ionela Lacramioara Serban, Irina Dobrin, Mihai Apostu and Romeo Petru Dobrin

Medicina 2025, 61(7), 1211; https://doi.org/10.3390/medicina61071211 - 3 Jul 2025

Cited by 4 | Viewed by 5318

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with chronic inattention, hyperactivity, and impulsivity and is linked with significant functional impairment. Despite being highly prevalent, diagnosis of ADHD continues to rely on subjective assessment reports of behavior and is often delayed or inaccurate. [...] Read more.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with chronic inattention, hyperactivity, and impulsivity and is linked with significant functional impairment. Despite being highly prevalent, diagnosis of ADHD continues to rely on subjective assessment reports of behavior and is often delayed or inaccurate. This review summarizes current advances in biomarkers and neuropsychological tests for the improvement of ADHD diagnosis and treatment. Key biomarkers are neuroimaging methods (e.g., structural and functional MRI), electrophysiological measures (e.g., EEG, ERP), and biochemical measures (e.g., cortisol, vitamin D). Additionally, novel experimental measures, e.g., eye-tracking, pupillometry, and microbiome analysis, hold the promise to be objective and dynamic measures of ADHD symptoms. The review also comments on the impact of the burden of ADHD on quality of life, e.g., emotional well-being, academic achievement, and social functioning. Additionally, differences between individuals, such as age, sex, comorbidities, and the impact of social and family support, are also addressed in relation to ADHD outcomes. In summary, we highlight the potential of these emerging biomarkers and tools to revolutionize ADHD diagnosis and guide personalized treatment strategies. These insights have significant implications for improving patient outcomes. Full article

(This article belongs to the Section Psychiatry)

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12 pages, 1740 KB

Open AccessEditor’s ChoiceArticle

Which B2 Fractures Can Be Treated with ORIF? Validation of the “Beyond the Vancouver Classification”

by Karl Stoffel, Martin Clauss and Marlene Mauch

Medicina 2025, 61(7), 1138; https://doi.org/10.3390/medicina61071138 - 24 Jun 2025

Cited by 3 | Viewed by 1306

Abstract

Background and objectives: The objective was to validate the Beyond the Vancouver classification. Based on this algorithm, it was hypothesized that cemented polished tapered stems with an intact cement mantle and cementless stable stems with defined criteria could be classified as stable and [...] Read more.

Background and objectives: The objective was to validate the Beyond the Vancouver classification. Based on this algorithm, it was hypothesized that cemented polished tapered stems with an intact cement mantle and cementless stable stems with defined criteria could be classified as stable and therefore treated with open reduction and internal fixation (ORIF). Materials and Methods: This retrospective, single-center cohort study re-analyzed patients initially diagnosed with Vancouver type B2 fractures treated with ORIF between 2007 and 2020. Clinical and radiological outcomes were extracted from medical reports. A combined radiological and clinical score was used as the main outcome measure. Patients categorized according to the Beyond the Vancouver classification were compared for functional outcome. Results: 42 patients (25 male, 17 female) with a median (range) age of 83 years (75–88 years) and follow-up time of 25 weeks (12–35 weeks) were reviewed. It was found that ORIF achieved excellent or good results in 81% of cases for stems classified as stable (n = 16) and in 30% of cases for stems classified as loose (n = 23). Successful cases (30%), although classified as loose, all had the same fracture pattern: an intact greater trochanter and a fracture fragment attached laterally to the stem with distal fixation of the stem. Conclusions: This case series suggests that certain Vancouver B2 fractures can be treated with ORIF. The Beyond the Vancouver classification may support the categorization of ‘stable’ and ‘loose’ stems. The validity of the algorithm was supported by the observation that ORIF provided excellent and good results for the majority of stems classified as ‘stable’, but poor results for stems classified as ‘loose’. Furthermore, the fracture pattern has been shown to be a crucial factor that should be considered when treating distally fixed cementless stems. The classification was therefore expanded to include the specific fracture patterns in cementless distally fixed stems that can be successfully treated with ORIF. The Beyond the Vancouver classification can provide further guidance in the identification of ‘loose’ or ‘stable’ stems. Full article

(This article belongs to the Section Orthopedics)

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35 pages, 8088 KB

Open AccessEditor’s ChoiceSystematic Review

Mind over Malignancy: A Systematic Review and Meta-Analysis of Psychological Distress, Coping, and Therapeutic Interventions in Oncology

by Ana Maria Paslaru, Alina Plesea-Condratovici, Lavinia-Alexandra Moroianu, Oana-Maria Isailă, Laura Florentina Rebegea, Liliana Lacramioara Pavel and Anamaria Ciubară

Medicina 2025, 61(6), 1086; https://doi.org/10.3390/medicina61061086 - 13 Jun 2025

Cited by 12 | Viewed by 6182

Abstract

Background and Objectives: Psychological distress is a pervasive yet often undertreated aspect of the cancer experience, contributing to reduced quality of life, poorer treatment adherence, and worse health outcomes. This systematic review and meta-analysis evaluated the efficacy of non-pharmacological, evidence-based psychological interventions on [...] Read more.

Background and Objectives: Psychological distress is a pervasive yet often undertreated aspect of the cancer experience, contributing to reduced quality of life, poorer treatment adherence, and worse health outcomes. This systematic review and meta-analysis evaluated the efficacy of non-pharmacological, evidence-based psychological interventions on distress, depression, anxiety, coping capacity, and quality of life in adult cancer patients. Interventions were grouped into three domains: structured psychotherapeutic therapies (e.g., Cognitive Behavioral Therapy [CBT], Acceptance and Commitment Therapy [ACT], Meaning-Centered Psychotherapy [MCP]); mindfulness and stress reduction programs (e.g., Mindfulness-Based Stress Reduction [MBSR], Mindfulness-Based Cognitive Therapy [MBCT]); and coping and resilience-enhancing modalities (e.g., Promoting Resilience in Stress Management [PRISM], expressive writing). Materials and Methods: Following PRISMA guidelines, 42 randomized controlled trials published between 2015 and 2025 were included. A stratified meta-analytic approach calculated pooled standardized mean differences for each intervention class and outcome. Heterogeneity, subgroup, and moderator analyses explored drivers of effect variability. Results: Structured psychotherapeutic interventions yielded the largest effects, especially for depression. Mindfulness-based interventions produced moderate but significant improvements in distress and emotional regulation. Coping and resilience programs provided smaller yet statistically significant gains in adaptive coping. Between-study heterogeneity was moderate, partly explained by intervention type, delivery modality, and cancer subtype. Conclusions: These findings support integrating psychosocial care into standard oncology protocols and endorse its routine implementation as a core component of comprehensive cancer treatment. Full article

(This article belongs to the Special Issue New Insights into the Diagnosis, Management, and Interventions of Mood Disorders)

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12 pages, 838 KB

Open AccessEditor’s ChoiceArticle

Impact of Para-Aortic Lymphadenectomy on Clinically FIGO Stage IIIC1 High-Grade Endometrial Cancer: A Retrospective Cohort Study from Two Tertiary Centers in Korea and Taiwan

by Yen-Ling Lai, Jun-Hyeong Seo, Koping Chang, Hyun-Soo Kim, Jung Chen, Tyan-Shin Yang, Yu-Li Chen and Yoo-Young Lee

Medicina 2025, 61(6), 1079; https://doi.org/10.3390/medicina61061079 - 12 Jun 2025

Cited by 2 | Viewed by 1663

Abstract

Background and Objectives: The therapeutic effect of para-aortic lymphadenectomy in patients with clinically para-aortic node-negative diseases remains controversial. In this study, we investigated whether combined pelvic and para-aortic lymphadenectomy has a survival benefit compared with pelvic lymphadenectomy alone in patients with clinically [...] Read more.

Background and Objectives: The therapeutic effect of para-aortic lymphadenectomy in patients with clinically para-aortic node-negative diseases remains controversial. In this study, we investigated whether combined pelvic and para-aortic lymphadenectomy has a survival benefit compared with pelvic lymphadenectomy alone in patients with clinically FIGO stage IIIC1 high-grade endometrial cancer. Materials and Methods: We retrospectively reviewed patients with clinically FIGO stage IIIC1 high-grade endometrial cancer in the period between January 2000 and December 2020 at two tertiary centers. The patients were stratified according to type of lymphadenectomy and subgroup analyses performed. Kaplan–Meier analysis and a Cox proportional-hazards model were used to evaluate survival outcomes. Results: A total of 56 patients were identified. Of these patients, 18 underwent pelvic lymphadenectomy alone and 38 underwent combined pelvic and para-aortic lymphadenectomy. After staging surgery, 34 (60.7%) patients had pathologically confirmed lymph node metastases. Within a median follow-up of 57.5 months, there were no significant differences in recurrence-free survival (RFS) and overall survival (OS) between the two groups. In subgroup analyses, the node- and lymphovascular space invasion (LVSI)-positive patients characterized by grade 3 endometrioid histologic type (p = 0.010) or negative peritoneal washing cytology (p = 0.035) had an RFS benefit from combined pelvic and para-aortic lymphadenectomy. Conclusions: The addition of para-aortic lymphadenectomy to pelvic lymphadenectomy did not improve survival in patients with clinically FIGO IIIC1 endometrial cancer. However, para-aortic lymphadenectomy may have RFS benefit for patients with grade 3 endometrioid histologic type and positive LVSI. Full article

(This article belongs to the Special Issue Endometrial Cancer: Biomarkers and Management)

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14 pages, 2937 KB

Open AccessEditor’s ChoiceReview

Use of JAK Inhibitors in Lichen Planus: An Update

by Dario Didona, Raffaele Dante Caposiena Caro, Laura Calabrese, Martina D’Onghia, Giulia Galluccio, Matteo Riccardo Di Nicola, Alessandra Rallo and Giovanni Paolino

Medicina 2025, 61(6), 1056; https://doi.org/10.3390/medicina61061056 - 8 Jun 2025

Cited by 4 | Viewed by 6095

Abstract

Lichen planus (LP) is a chronic inflammatory disorder affecting approximately 1% of the population. It presents with a wide range of clinical manifestations, mainly involving the skin, mucosal surfaces, and skin appendages, and is often characterized by a relapsing course and variable response [...] Read more.

Lichen planus (LP) is a chronic inflammatory disorder affecting approximately 1% of the population. It presents with a wide range of clinical manifestations, mainly involving the skin, mucosal surfaces, and skin appendages, and is often characterized by a relapsing course and variable response to treatment. Although several therapeutic strategies are available, many are off-label and show limited efficacy in resistant forms. Increasing evidence points to the central role of the JAK/STAT signaling pathway in the immunopathogenesis of LP, with cytokines such as interferon-gamma and interleukin-21 playing key roles in sustaining chronic inflammation. Based on this rationale, Janus kinase (JAK) inhibitors have recently been proposed as potential therapeutic agents in LP. This review explores the biological basis for their use and systematically summarizes the existing clinical evidence on the use of JAK inhibitors in cutaneous, mucosal, appendageal, and nail variants of LP. The preliminary data suggests favorable outcomes in many patients with difficult-to-treat disease, with an acceptable safety profile. Further prospective trials are needed to establish their definitive role in the management of LP. Full article

(This article belongs to the Special Issue Chronic Inflammatory Skin Diseases: Where We Are and Where We Are Going: 2nd Edition)

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29 pages, 1335 KB

Open AccessEditor’s ChoiceSystematic Review

Metformin: A Dual-Role Player in Cancer Treatment and Prevention: A Comprehensive Systematic Review and Meta-Analysis

by Imran Rangraze, Adil Farooq Wali, Mohamed El-Tanani, Mohamed Anas Patni, Syed Arman Rabbani, Rasha Babiker, Shakta Mani Satyam, Yahia El-Tanani and Manfredi Rizzo

Medicina 2025, 61(6), 1021; https://doi.org/10.3390/medicina61061021 - 30 May 2025

Cited by 5 | Viewed by 8398

Abstract

Background and Objectives: Metformin is said to reduce the incidences and deaths resulting from cancer in patients suffering from type 2 diabetes mellitus, but the results have been inconsistent. Perform a systematic review and meta-analysis concentrating on the different outcomes of several [...] Read more.

Background and Objectives: Metformin is said to reduce the incidences and deaths resulting from cancer in patients suffering from type 2 diabetes mellitus, but the results have been inconsistent. Perform a systematic review and meta-analysis concentrating on the different outcomes of several cancers while taking into account the impact of metformin use. Materials and Methods: As of 15 October 2024, the literature for Medline, Embase, and Web of Science was systematically searched. ROBINS-I and the RoB 2 tool were used for assessing the risk of bias in observational studies and randomized controlled trials (RCTs), respectively. The strength of the evidence with respect to the GRADE criteria was checked. Random effects meta-analyses were conducted alongside sensitivity analyses, subgroup analyses, and meta-regressions. By utilizing funnel plots as well as Egger’s test and trim-and-fill analysis, publication bias was evaluated. Results: In total, 65 studies were included in the final analyses: Metformin intake was linked to a lower risk of cancer (RR 0.72; 95% CI: 0.64–0.81, I² = 45%). Significant reductions were observed in breast cancer (RR 0.68; 95% CI: 0.55–0.83) and colorectal cancers (RR 0.62; 95% CI: 0.51–0.76). Evidence certainty fluctuated from moderate to low, though analyses confirmed the results. Plofs funded the publication bias, but adjustment in trim-and-fill did not change the outcome significantly. Conclusions: Metformin intake seems to lower the chances of developing several types of cancers, especially breast and colorectal cancers, but the observational designs hinder determining the causal factors for observational studies. There is a need for large RCTs. Full article

(This article belongs to the Special Issue Addressing the Changes and Innovations in the Treatment of Gynecological Cancers)

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13 pages, 2691 KB

Open AccessEditor’s ChoiceArticle

Arthroscopic Resection of Infrapatellar Fat Pad Impingement Syndrome: Long-Term Clinical Results at Minimum 10-Year Follow-Up

by Young-Cheol Park, Young-Mo Kim and Yong-Bum Joo

Medicina 2025, 61(6), 997; https://doi.org/10.3390/medicina61060997 - 28 May 2025

Cited by 4 | Viewed by 4339

Abstract

Background and Objectives: Infrapatellar fat pad impingement syndrome (IFPIS) is a relatively underdiagnosed cause of anterior knee pain. While conservative management is the initial approach, some patients require surgical intervention. This study aimed to evaluate the long-term clinical and radiologic outcomes following [...] Read more.

Background and Objectives: Infrapatellar fat pad impingement syndrome (IFPIS) is a relatively underdiagnosed cause of anterior knee pain. While conservative management is the initial approach, some patients require surgical intervention. This study aimed to evaluate the long-term clinical and radiologic outcomes following arthroscopic resection of the infrapatellar fat pad in patients with IFPIS. Materials and Methods: Eighteen patients (10 females, 8 males; median age 22) diagnosed with IFPIS and unresponsive to conservative therapy underwent arthroscopic partial or subtotal resection between 2007 and 2013. Diagnosis was based on physical examination (Hoffa’s test), MRI findings, and response to lidocaine injection. Clinical outcomes (VAS, IKDC-2000, Kujala, Lysholm, Tegner activity scores) and radiologic assessments (ISR, CDI, PFJ osteoarthritis grade) were evaluated preoperatively, at 2 years, and at a final follow-up (mean 148.7 months). Results: All clinical scores significantly improved postoperatively. VAS decreased from 7.25 ± 0.79 to 2.43 ± 1.50 at 2 years, and to 3.66 ± 1.50 at the final follow-up (p < 0.001). Similar long-term improvements were observed in the Kujala, IKDC-2000, Lysholm, and Tegner scores (all p < 0.001). Radiographic parameters including ISR and CDI remained stable, and there was no statistically significant progression in patellofemoral osteoarthritis. However, 5 of 18 patients (27.8%) reported persistent symptoms at long-term follow-up. Conclusions: Arthroscopic resection of the infrapatellar fat pad in patients with IFPIS showed favorable and sustained clinical outcomes over a 10-year follow-up, without significant radiological changes. These results suggest that arthroscopic resection is a viable treatment option when accurate diagnosis is established. Full article

(This article belongs to the Section Orthopedics)

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20 pages, 694 KB

Open AccessEditor’s ChoiceReview

Standardized Definition of Red Flags in Musculoskeletal Care: A Comprehensive Review of Clinical Practice Guidelines

by Lorenzo Storari, Jennifer Piai, Mirko Zitti, Graziano Raffaele, Fabio Fiorentino, Rachele Paciotti, Fabiola Garzonio, Giulia Ganassin, James Dunning, Giacomo Rossettini, Daniel Feller, John D. Heick, Firas Mourad and Filippo Maselli

Medicina 2025, 61(6), 1002; https://doi.org/10.3390/medicina61061002 - 28 May 2025

Cited by 4 | Viewed by 10076

Abstract

Background and Objectives: The aging population and the COVID-19 pandemic have led to a rise in severe conditions, including musculoskeletal (MSK) disorders. Although MSK conditions are often managed in primary care, they may sometimes mask serious illnesses requiring urgent diagnosis. The red flag [...] Read more.

Background and Objectives: The aging population and the COVID-19 pandemic have led to a rise in severe conditions, including musculoskeletal (MSK) disorders. Although MSK conditions are often managed in primary care, they may sometimes mask serious illnesses requiring urgent diagnosis. The red flag (RF) concept is essential for identifying signs and symptoms of potentially severe disease. However, RF criteria vary across clinical guidelines and lack consistency. With the growing role of direct access to physiotherapy—bypassing physician referral—physiotherapists must develop strong differential diagnostic skills to identify serious pathologies that mimic MSK disorders. This review aims to systematically map how RFs are defined in MSK clinical practice guidelines (CPGs), supporting the move toward a standardized definition for clinical and research use. Materials and Methods: A comprehensive literature search was conducted in PubMed, Web of Science, Scopus, and Cochrane databases. Included studies were CPGs and systematic reviews (SRs) of CPGs addressing MSK disorders and incorporating the RF concept. Data extraction followed a rigorous process, and RF definitions were synthesized and compared in table format. Results: Out of thirteen-thousand three-hundred and ninety-three articles identified, fourteen met inclusion criteria (seven CPGs and seven SRs of CPGs), spanning both physiotherapy and medical fields. All definitions described RFs as signs or symptoms indicating possible serious pathology requiring further investigation or referral. Some definitions referred broadly to “patterns of signs or symptoms”, while others offered more precise criteria. Conclusions: This review highlights the lack of a standardized RF definition in MSK care, leading to inconsistencies in clinical decision-making and diagnosis. To improve patient safety and guide clinicians—especially in direct-access contexts—a unified, internationally recognized definition of RFs is needed in future guidelines. Full article

(This article belongs to the Special Issue Physical Therapy: A New Perspective)

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10 pages, 2507 KB

Open AccessEditor’s ChoiceArticle

The Clinical Outcomes of a Bioinductive Collagen Implant in Bursal-Sided Partial-Thickness Rotator Cuff Tears

by Jaesung Yoo and Daehee Lee

Medicina 2025, 61(6), 988; https://doi.org/10.3390/medicina61060988 - 27 May 2025

Cited by 2 | Viewed by 3508

Abstract

Background and Objectives: Many middle-aged and older individuals experience shoulder pain, often due to partial-thickness rotator cuff tears (PTRCTs). If conservative treatment fails to relieve symptoms in a patient, surgical intervention may be necessary. In such cases, using a bioinductive collagen implant [...] Read more.

Background and Objectives: Many middle-aged and older individuals experience shoulder pain, often due to partial-thickness rotator cuff tears (PTRCTs). If conservative treatment fails to relieve symptoms in a patient, surgical intervention may be necessary. In such cases, using a bioinductive collagen implant may offer a viable alternative to conventional rotator cuff repair. Most notably, it offers potential advantages, particularly in reducing postoperative pain and promoting faster recovery. Accordingly, this study aims to evaluate the clinical outcomes of treating bursal-sided partial-thickness rotator cuff tears using bioinductive collagen implants alone, without concurrent rotator cuff repair. Materials and Methods: We followed 32 patients who had bursal-sided partial-thickness rotator cuff tears (Ellman grade I or II) and received conservative care for more than six months but continued to experience symptoms. These patients received surgery using bioinductive collagen implants without rotator cuff repair, and we followed up on their postoperative prognosis for at least one year after surgery. For a more accurate contrast, we performed clinical evaluation preoperatively and at 2 weeks, 6 weeks, 3 months, 6 months, and 12 months postoperatively. Visual Analog Scale (VAS), American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE), and Western Ontario Rotator Cuff (WORC) score were used as assessment tools in this study. As for radiological outcomes, magnetic resonance imaging (MRI) and ultrasonography were helpful. This supported our assessment of graft integration and failure. Results: These 32 patients included 13 with Ellman grade I tear and 19 with grade II tear. In both cases, they underwent surgery only using bioinductive collagen implants, and any anchor-based cuff repair was completely excluded. As for VAS (3.8 ± 2.9), certain statistically significant improvements were found starting at 2 weeks postoperatively. On the other hand, the scores of ASES (58.6 ± 20.3), SANE (60.1 ± 23.2), and WORC (59.8 ± 22.4) began to indicate a significant improvement starting at 6 weeks postoperatively (p < 0.001), showing continuous progress. At each final step, we confirmed that there were no cases of graft failure by radiological evaluation and found successful healing indicators, such as much less pain in all patients. Conclusions: The findings of this study provide the clinical evidence that a surgery using bioinductive collagen implant for bursal-sided partial-thickness rotator cuff tears is a highly effective treatment option in patients unresponsive to conservative therapy. Particularly, its practical clinical effectiveness includes facilitating rapid recovery without a significant risk of complications. Full article

(This article belongs to the Special Issue Advancement in Upper Limb Rehabilitation and Injury Prevention)

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25 pages, 10080 KB

Open AccessEditor’s ChoiceArticle

CBX1 as a Prognostic Biomarker and Therapeutic Target in Liver Hepatocellular Carcinoma: Insight into DNA Methylation and Non-Coding RNA Networks from Comprehensive Bioinformatics Analysis

by Hye-Ran Kim and Jongwan Kim

Medicina 2025, 61(6), 983; https://doi.org/10.3390/medicina61060983 - 26 May 2025

Cited by 4 | Viewed by 1328

Abstract

Background and Objectives: Chromobox 1 (CBX1), a key epigenetic regulator involved in chromatin remodeling, has been implicated in various cancers; however, its role in liver hepatocellular carcinoma (LIHC) remains underexplored. This study aimed to investigate the expression patterns, epigenetic regulation, and non-coding [...] Read more.

Background and Objectives: Chromobox 1 (CBX1), a key epigenetic regulator involved in chromatin remodeling, has been implicated in various cancers; however, its role in liver hepatocellular carcinoma (LIHC) remains underexplored. This study aimed to investigate the expression patterns, epigenetic regulation, and non-coding RNA (ncRNA) networks involving CBX1 in LIHC, assess their potential as diagnostic and prognostic biomarkers, and explore their relevance as a putative therapeutic target. Materials and Methods: A multi-omics bioinformatics approach was employed using datasets from GEPIA2, OncoDB, UALCAN, Human Protein Atlas, KM Plotter, MethSurv, miRNet, and ENCORI. These databases were used to analyze mRNA and protein expression, DNA methylation, prognosis, and interaction networks involving CBX1 and ncRNAs. Results: CBX1 was significantly upregulated in both the mRNA and protein expression in LIHC. Upregulated CBX1 expression was associated with poor prognosis. DNA methylation analysis revealed that both hypermethylated and hypomethylated probes were significantly associated with CBX1 expression and poor prognosis. hsa-miR-212-3p and hsa-miR-132-3p were significantly upregulated in LIHC and were positively correlated with CBX1 expression and poor prognosis. The ncRNA network was identified, including long ncRNAs, circular RNAs, and pseudogenes, many of which were linked to tumor progression and poor prognosis, and competing endogenous RNAs were associated with tumor progression and poor prognosis in LIHC. Conclusions: CBX1 was significantly overexpressed in LIHC and was regulated by both DNA methylation and ncRNA interactions. Its expression is closely associated with a poor prognosis. The CBX1–micro-RNA–long ncRNA/circular RNA axis is a promising avenue for the development of novel diagnostic and therapeutic strategies. This study provides system-level insights into the regulatory landscape of CBX1 in LIHC and supports its potential role in precision medicine. Full article

(This article belongs to the Section Oncology)

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50 pages, 1233 KB

Open AccessEditor’s ChoiceReview

From Nature to Nanomedicine: Enhancing the Antitumor Efficacy of Rhein, Curcumin, and Resveratrol

by Ana-Maria Trofin, Dragoș Viorel Scripcariu, Silviu-Iulian Filipiuc, Anca-Narcisa Neagu, Leontina-Elena Filipiuc, Bogdan-Ionel Tamba, Madalina Maria Palaghia and Cristina Mariana Uritu

Medicina 2025, 61(6), 981; https://doi.org/10.3390/medicina61060981 - 26 May 2025

Cited by 14 | Viewed by 4611

Abstract

Natural compounds have garnered increasing interest as potential antitumor agents due to their multifaceted biological activities and relatively low toxicity profiles. This review focuses on three well-studied natural molecules: rhein, curcumin, and resveratrol, analyzing and comparing their antitumor potential across a variety of [...] Read more.

Natural compounds have garnered increasing interest as potential antitumor agents due to their multifaceted biological activities and relatively low toxicity profiles. This review focuses on three well-studied natural molecules: rhein, curcumin, and resveratrol, analyzing and comparing their antitumor potential across a variety of cancer models. For each compound, we present an integrated perspective encompassing natural sources, physicochemical properties, pharmacological and pharmacokinetic characteristics, and the latest in vitro and in vivo evidence of anticancer activity. Special attention is given to the molecular mechanisms underlying their antitumor effects, including the modulation of cell cycle regulators, induction of apoptosis, inhibition of metastasis and angiogenesis, and regulation of key signaling pathways such as NF-κB, PI3K/Akt/mTOR, STAT3, and MAPKs. Although numerous studies highlighted their therapeutic promise, significant barriers remain—particularly related to poor solubility and limited bioavailability—which have hindered clinical translation, especially in the case of rhein. Advances in nanotechnology-based drug delivery systems offer promising solutions to these limitations, enabling improved targeting and enhanced efficacy. This review underscores the need for continued preclinical and clinical investigations to fully elucidate the therapeutic value of these compounds and support their integration into modern oncological treatment strategies. Full article

(This article belongs to the Special Issue Advances in Cancer Multimodal Approaches: Biomarkers, Mechanisms, Surgical Procedures and Oncological Therapies, 2nd Edition)

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15 pages, 303 KB

Open AccessEditor’s ChoiceReview

The Role of Skin Substitutes in the Therapeutical Management of Burns Affecting Functional Areas

by Matei Iordache, Luca Avram, Ioan Lascar and Adrian Frunza

Medicina 2025, 61(6), 947; https://doi.org/10.3390/medicina61060947 - 22 May 2025

Cited by 3 | Viewed by 5173

Abstract

Considered one of the most severe types of trauma with a high impact upon patient survival, burns are the leading cause of disability-adjusted life-years (DALYs), and are responsible for high morbidity, prolonged hospitalization, disfigurement and social stigma. Of particular interest are injuries that [...] Read more.

Considered one of the most severe types of trauma with a high impact upon patient survival, burns are the leading cause of disability-adjusted life-years (DALYs), and are responsible for high morbidity, prolonged hospitalization, disfigurement and social stigma. Of particular interest are injuries that affect the functional areas: face, neck, hand and fingers, joints, feet and soles and perineum. Burns to these regions highly influence the day-to-day activities of patients due to the formation of vicious scars and contractures, which may affect both quality of life and functional capacity. One of the primary challenges in the management of burn patients is the effective coverage of tissue defects resulting from such injuries. Cases that have a large area of burned surface also have a limited amount of total available skin. As such, the importance of skin substitutes increases, particularly in the treatment of these areas. Skin substitutes are widely utilized in plastic surgery due to their ability to promote wound healing by providing an extracellular matrix. Consequently, ongoing research has focused on developing skin substitutes that can serve as alternatives to autografts, addressing the challenges associated with large-scale tissue loss. This article aims to present and compare the most used skin substitutes, highlighting their respective advantages and limitations. This topic continues to be a subject of significant debate, as an ideal substitute has yet to be created. The cost–efficiency ratio is a practical consideration that must be tailored to each specific medical system. The available data in the literature usually present general guidelines, not rules, and as such, they need to be adapted to each patient’s necessities. Full article

(This article belongs to the Special Issue Recent Research and Trends in Plastic, Aesthetic and Regenerative Surgery)

19 pages, 2245 KB

Open AccessEditor’s ChoiceArticle

Core Exercise as Non-Pharmacological Strategy for Improving Metabolic Health in Prediabetic Women

by Nuray Yiğiter, Faruk Akçınar, Yavuz Yasul, Vedat Çınar, Taner Akbulut and Gian Mario Migliaccio

Medicina 2025, 61(5), 942; https://doi.org/10.3390/medicina61050942 - 21 May 2025

Cited by 5 | Viewed by 3338

Abstract

Background and Objectives: Prediabetes (PD) is characterized by impaired glucose metabolism and is associated with an elevated risk of type 2 diabetes and cardiovascular diseases. This study aimed to investigate the effects of an 8-week core exercise intervention on glycemic control, lipid [...] Read more.

Background and Objectives: Prediabetes (PD) is characterized by impaired glucose metabolism and is associated with an elevated risk of type 2 diabetes and cardiovascular diseases. This study aimed to investigate the effects of an 8-week core exercise intervention on glycemic control, lipid profiles, insulin sensitivity, body composition, and physical performance in prediabetic women. Materials and Methods: Eighteen prediabetic women aged 20–55 years were randomly allocated to either a core exercise group (n = 9) or a control group (n = 9). The intervention group completed 24 supervised core exercise sessions over 8 weeks, whereas the control group remained sedentary. Pre- and post-intervention evaluations included anthropometric measurements, flexibility and strength tests, fasting and postprandial glucose levels, HbA1c, insulin, HOMA-IR, lipid profiles, and serum iron levels. Non-parametric tests were used for statistical analysis, and a Principal Component Analysis (PCA) and hierarchical clustering were conducted to explore multidimensional metabolic changes. Results: Core exercise significantly improved the body weight, BMI, fat percentage, and circumferences (shoulder, chest, and hip), along with an enhanced flexibility and back-leg strength (p < 0.05). Glycemic indices (FBG, PBG, and HbA1c), insulin, and HOMA-IR levels were significantly reduced, while serum iron and HDL-C increased (p < 0.05). Lipid markers, including the TG, LDL-C, CHOL, and TG/HDL-C ratio, showed significant improvements. The PCA and cluster analyses identified three clusters reflecting metabolic risk, body composition, and protective factors. Conclusions: This study demonstrates that an 8-week structured core exercise program significantly improves glycemic control, lipid profiles, insulin sensitivity, and body composition in women with prediabetes. Multivariate analyses (PCA and hierarchical clustering) corroborate a metabolic shift towards a reduced insulin resistance and a more favorable cardiometabolic profile, supporting core training as a viable, evidence-based non-pharmacological intervention to mitigate metabolic risk. Full article

(This article belongs to the Special Issue Novel Innovations in Diabetes Mellitus Prevention, Screening and Management)

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11 pages, 1630 KB

Open AccessEditor’s ChoiceArticle

Clinical Effectiveness, Clinical Stability, and Effects on Serum Galectin-7 Levels of Dupilumab and JAK Inhibitors in Moderate-to-Severe Atopic Dermatitis: A Real-World, Single-Center Analysis

by Akihiro Horie, Tomomitsu Miyagaki, Chikako Hiranuma, Mami Iijima, Yoshiaki Hara, Shinya Oba, Mina Hashimoto, Reina Omori, Tatsuro Okano and Takafumi Kadono

Medicina 2025, 61(5), 926; https://doi.org/10.3390/medicina61050926 - 20 May 2025

Cited by 2 | Viewed by 1727

Abstract

Background and Objectives: Several biologics and oral Janus kinase (JAK) inhibitors have been developed and shown in clinical trials and real-world studies to be effective and safe in moderate-to-severe atopic dermatitis (AD). In this study, we aimed to evaluate the real-world outcomes of [...] Read more.

Background and Objectives: Several biologics and oral Janus kinase (JAK) inhibitors have been developed and shown in clinical trials and real-world studies to be effective and safe in moderate-to-severe atopic dermatitis (AD). In this study, we aimed to evaluate the real-world outcomes of patients with moderate-to-severe AD treated with dupilumab and JAK inhibitors in our facility, focusing on their short-term effect on serum galectin-7 levels, a biomarker reflecting skin barrier impairment, and one-year stability based on patient-oriented outcomes. Materials and Methods: In a single-center, retrospective study of AD patients treated with dupilumab or JAK inhibitors between January 2018 and December 2024, we assessed physician-oriented outcomes until 16 weeks and patient-oriented outcomes until 52 weeks. Serum galectin-7 levels at baseline and 4 and/or 16 weeks after treatment were measured in 14 patients. Results: A total of 45 patients starting dupilumab and 10 patients starting JAK inhibitors were enrolled. Percentage reductions in EASI scores from baseline at 4, 8, and 16 weeks were 58.36 ± 22.09, 69.59 ± 20.96, and 75.98 ± 19.70, with no significant differences between patients treated with dupilumab and JAK inhibitors. Serum galectin-7 levels were significantly reduced after treatment at 4 and 16 weeks in the entire population. Both DLQI and POEM scores were reduced at 4 weeks and gradually decreased until 52 weeks. The reduction was faster with JAK inhibitors than with dupilumab. Visits with unstable effectiveness, defined as a visit with a three-point or greater increase in the POEM score at 28, 40, and 52 weeks, were more frequent in JAK inhibitor patients. Conclusions: Both dupilumab and JAK inhibitors showed high effectiveness on skin inflammation and decreased a marker of skin barrier dysfunction within 16 weeks. JAK inhibitors improved patient-reported outcomes more quickly than dupilumab, but instability of effectiveness during 16 and 52 weeks was higher with JAK inhibitors. Full article

(This article belongs to the Special Issue Chronic Inflammatory Skin Diseases: Where We Are and Where We Are Going: 2nd Edition)

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12 pages, 18426 KB

Open AccessEditor’s ChoiceArticle

Osteogenic Potential and Bone Matrix Maturity: Comparison of Demineralized Bone Matrix and P15 Polypeptide iFactor^® in an In Vitro Study

by Anell Olivos-Meza, Monica Maribel Mata-Miranda, Marcelo Robles-Rodríguez, Gustavo Jesús Vázquez-Zapién, Melissa Guerrero-Ruiz and Carlos Landa-Solís

Medicina 2025, 61(5), 914; https://doi.org/10.3390/medicina61050914 - 18 May 2025

Cited by 3 | Viewed by 1479

Abstract

Background and Objectives: Demineralized bone matrix (DBM) is a widely used bone graft substitute due to its osteoconductive and osteoinductive properties. However, its efficacy varies due to differences in donor, processing, and storage conditions. Synthetic alternatives, such as iFactor^®, combine non-organic [...] Read more.

Background and Objectives: Demineralized bone matrix (DBM) is a widely used bone graft substitute due to its osteoconductive and osteoinductive properties. However, its efficacy varies due to differences in donor, processing, and storage conditions. Synthetic alternatives, such as iFactor^®, combine non-organic bone mineral and a small peptide (P-15) to enhance the cellular attachment and osteogenesis. To compare the osteogenic potential and bone matrix maturity of iFactor^® and a commercial DBM scaffold through calcium nodule formation and Fourier transform infrared spectroscopy (FTIR) analysis. Materials and Methods: Human mesenchymal stem cells (hMSCs) were cultured and exposed to iFactor^® or DBM in paracrine culture conditions for 21 days. Calcium nodule formation was assessed using alizarin red staining and quantified spectrophotometrically. The FTIR analysis of hMSCs exposed to the scaffolds for three months evaluated the biomolecular composition and bone matrix maturity. Results: Calcium nodules formed in both groups but in smaller quantities than in the positive control (p < 0.05). The biomolecular components of the DBM were similar to healthy bone (p > 0.05) than those of the iFactor^® group (p < 0.005). A different rate of bone regeneration was observed through the formation of a greater number of calcium nodule aggregates identified in the extracellular matrix of mesenchymal stem cell cultures exposed to iFactor^® compared to those cultures enriched with DBM. Conclusions: Both experimental matrices demonstrated similar osteogenic potential at the 3-month follow-up. Although DBM has a closer biomolecular composition and carbonate substitution compared to healthy bone, iFactor^® showed faster matrix maturity expressed through the formation of a greater number of calcium nodule aggregates and higher hMSCs proliferation. Full article

(This article belongs to the Section Orthopedics)

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35 pages, 1235 KB

Open AccessEditor’s ChoiceReview

Multimodal Prehabilitation in Major Abdominal Surgery—Rationale, Modalities, Results and Limitations

by George Andrei Popescu, Dana Galieta Minca, Nader Mugurel Jafal, Cristian Valentin Toma, Sorin Tiberiu Alexandrescu, Radu Virgil Costea and Catalin Vasilescu

Medicina 2025, 61(5), 908; https://doi.org/10.3390/medicina61050908 - 17 May 2025

Cited by 12 | Viewed by 5833

Abstract

Recent evidence revealed that an adequate preoperative physiological reserve is crucial to overcome surgical stress response. Consequently, a new concept, called prehabilitation, emerged, aiming to improve the preoperative functional reserve of patients who will undergo major abdominal surgery. During the interval between diagnosis [...] Read more.

Recent evidence revealed that an adequate preoperative physiological reserve is crucial to overcome surgical stress response. Consequently, a new concept, called prehabilitation, emerged, aiming to improve the preoperative functional reserve of patients who will undergo major abdominal surgery. During the interval between diagnosis and surgery, a multimodal approach consisting of physical exercise and nutritional and psychological support could be employed to enhance physiologic reserve. Physical activity interventions aim to improve aerobic capacity, muscle strength and endurance. Nutritional support addressing malnutrition and sarcopenia also contributes to the achievement of the above-mentioned goals, particularly in patients undergoing cancer-related procedures. Psychological interventions targeting anxiety, depression and self-efficacy, as well as risk behavior modification (e.g., smoking cessation) seem to enhance recovery. However, there is a lack of standardization regarding these interventions, and the evidence about the impact of this multidisciplinary approach on the postoperative outcomes is still contradictory. This narrative review focuses on the physiological basis of surgical stress response and on the efficacy of prehabilitation, reflected mainly in the length of hospitalization and rates of postoperative complications. Multidisciplinary collaboration between surgeons, nutritionists, psychologists and physiotherapists was identified as the key to the success of prehabilitation programs. Synergizing prehabilitation and ERAS protocols significantly improves short-term surgical outcomes. Recent well-designed, randomized clinical trials revealed that this approach not only enhanced functional reserve, but also decreased the rates of postoperative complications and enhanced patient’s overall quality of life, emphasizing the importance of its implementation in routine, elective, surgical care. Full article

(This article belongs to the Section Surgery)

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19 pages, 347 KB

Open AccessEditor’s ChoiceReview

Bone Marrow Aspirate Concentrate (BMAC) for Knee Osteoarthritis: A Narrative Review of Clinical Efficacy and Future Directions

by Dojoon Park, Hae-Seok Koh, Youn-Ho Choi and Ilkyu Park

Medicina 2025, 61(5), 853; https://doi.org/10.3390/medicina61050853 - 6 May 2025

Cited by 8 | Viewed by 7789

Abstract

Bone marrow aspirate concentrate (BMAC) is an autologous regenerative therapy enriched with mesenchymal stem cells (MSCs) and bioactive growth factors, offering potential disease-modifying effects in knee osteoarthritis (OA). Compared to conventional intra-articular treatments, including hyaluronic acid (HA), platelet-rich plasma (PRP), and corticosteroids, BMAC [...] Read more.

Bone marrow aspirate concentrate (BMAC) is an autologous regenerative therapy enriched with mesenchymal stem cells (MSCs) and bioactive growth factors, offering potential disease-modifying effects in knee osteoarthritis (OA). Compared to conventional intra-articular treatments, including hyaluronic acid (HA), platelet-rich plasma (PRP), and corticosteroids, BMAC promotes cartilage regeneration, modulates inflammation, and enhances subchondral bone remodeling. Clinical evidence suggests that BMAC provides short- to mid-term symptomatic relief and functional improvement, with some studies indicating a potential to delay total knee arthroplasty (TKA). However, findings remain inconsistent, and long-term efficacy compared to PRP or autologous conditioned serum (ACS) is yet to be firmly established. Variability in BMAC preparation methods, injection protocols (single vs. repeated administration, intra-articular vs. subchondral delivery), and patient selection criteria complicates its clinical application, highlighting the need for standardized guidelines. Additionally, economic feasibility and cost-effectiveness concerns limit its widespread adoption. This review synthesizes current clinical evidence, evaluates optimal administration strategies, and explores future directions for improving treatment standardization and patient-specific therapy. Future research should prioritize well-designed, multicenter randomized controlled trials (RCTs) with long-term follow-up to confirm the sustained efficacy and therapeutic potential of BMAC in OA management. Full article

(This article belongs to the Special Issue State-of-the-Art Therapeutics and Imaging in Knee Surgery)

28 pages, 1773 KB

Open AccessEditor’s ChoiceReview

The Vaginal Microbiota, Human Papillomavirus, and Cervical Dysplasia—A Review

by Justė Kazlauskaitė, Guoda Žukienė, Vilius Rudaitis and Daiva Bartkevičienė

Medicina 2025, 61(5), 847; https://doi.org/10.3390/medicina61050847 - 5 May 2025

Cited by 8 | Viewed by 7271

Abstract

Background and Objectives: The relationship between the vaginal microbiota, human papillomavirus infection (HPV), and cervical precancerous lesions is a critical area of research, as it influences both the progression of HPV-related diseases and potential treatment strategies. New evidence suggests that Lactobacillus crispatus dominance [...] Read more.

Background and Objectives: The relationship between the vaginal microbiota, human papillomavirus infection (HPV), and cervical precancerous lesions is a critical area of research, as it influences both the progression of HPV-related diseases and potential treatment strategies. New evidence suggests that Lactobacillus crispatus dominance in the microbiota may protect against HPV persistence and speed the elimination of HPV. This study aims to explore the relationship between the vaginal microbiota composition and HPV infection, focusing on the impact of these factors on the development of cervical precancerous lesions. Materials and Methods: A comprehensive literature review was conducted using the PubMed database, focusing on studies that analyzed the association between the vaginal microbiota and HPV infection in the context of cervical dysplasia. This study was primarily based on clinical data on HPV integration in women with low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs), and cervical cancer. Results: Different types of vaginal microbiota communities (CSTs) have different pathogenic or protective potential. Healthy women predominantly exhibited CST I, with Lactobacillus crispatus as the dominant microorganism. CST IV, associated with increased anaerobic bacteria, was most common in HSIL and cervical cancer patients. Statistical analysis revealed that bacterial vaginosis (BV) was significantly associated with HPV persistence, with studies reporting a 1.8–3.4-fold increased risk (p < 0.05) of persistent HR-HPV infection in BV-positive women. Conclusions: Our literature review suggests that the composition of the vaginal microbiota can modulate the local immune response, the expression of viral oncogenes, and the integrity of the epithelial barrier. Furthermore, certain bacterial genes or metabolic pathways can be associated with a favorable or unfavorable outcome of the disease. Analysis of the vaginal microbiota could serve as an additional risk assessment tool, helping to distinguish between regressing and progressive precancerous conditions. Full article

(This article belongs to the Special Issue Addressing the Changes and Innovations in the Treatment of Gynecological Cancers)

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22 pages, 7258 KB

Open AccessEditor’s ChoiceArticle

AI in 2D Mammography: Improving Breast Cancer Screening Accuracy

by Sebastian Ciurescu, Simona Cerbu, Ciprian Nicușor Dima, Florina Borozan, Raluca Pârvănescu, Diana-Gabriela Ilaș, Cosmin Cîtu, Corina Vernic and Ioan Sas

Medicina 2025, 61(5), 809; https://doi.org/10.3390/medicina61050809 - 26 Apr 2025

Cited by 6 | Viewed by 5256

Abstract

Background and Objectives: Breast cancer is a leading global health challenge, where early detection is essential for improving survival outcomes. Two-dimensional (2D) mammography is the established standard for breast cancer screening; however, its diagnostic accuracy is limited by factors such as breast [...] Read more.

Background and Objectives: Breast cancer is a leading global health challenge, where early detection is essential for improving survival outcomes. Two-dimensional (2D) mammography is the established standard for breast cancer screening; however, its diagnostic accuracy is limited by factors such as breast density and inter-reader variability. Recent advances in artificial intelligence (AI) have shown promise in enhancing radiological interpretation. This study aimed to assess the utility of AI in improving lesion detection and classification in 2D mammography. Materials and Methods: A retrospective analysis was performed on a dataset of 578 mammographic images obtained from a single radiology center. The dataset consisted of 36% pathologic and 64% normal cases, and was partitioned into training (403 images), validation (87 images), and test (88 images) sets. Image preprocessing involved grayscale conversion, contrast-limited adaptive histogram equalization (CLAHE), noise reduction, and sharpening. A convolutional neural network (CNN) model was developed using transfer learning with ResNet50. Model performance was evaluated using sensitivity, specificity, accuracy, and area under the receiver operating characteristic (AUC-ROC) curve. Results: The AI model achieved an overall classification accuracy of 88.5% and an AUC-ROC of 0.93, demonstrating strong discriminative capability between normal and pathologic cases. Notably, the model exhibited a high specificity of 92.7%, contributing to a reduction in false positives and improved screening efficiency. Conclusions: AI-assisted 2D mammography holds potential to enhance breast cancer detection by improving lesion classification and reducing false-positive findings. Although the model achieved high specificity, further optimization is required to minimize false negatives. Future efforts should aim to improve model sensitivity, incorporate multimodal imaging techniques, and validate results across larger, multicenter prospective cohorts to ensure effective integration into clinical radiology workflows. Full article

(This article belongs to the Special Issue New Developments in Diagnosis and Management of Breast Cancer)

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10 pages, 2632 KB

Open AccessEditor’s ChoiceArticle

Relationship Between Intracranial Pressure, Ocular Blood Flow and Vessel Density: Insights from OCTA and Doppler Imaging

by Arminas Zizas, Keren Wood, Austėja Judickaitė, Vytautas Petkus, Arminas Ragauskas, Viktorija Bakstytė, Alon Harris and Ingrida Janulevičienė

Medicina 2025, 61(5), 800; https://doi.org/10.3390/medicina61050800 - 25 Apr 2025

Cited by 3 | Viewed by 1466

Abstract

Background and Objectives: Despite the growing amount of new research, the pathophysiology of glaucoma remains unclear. The aim of this study was to determine the relationship between intracranial pressure (ICP), ocular blood flow and structural optic nerve parameters. Materials and Methods: A [...] Read more.

Background and Objectives: Despite the growing amount of new research, the pathophysiology of glaucoma remains unclear. The aim of this study was to determine the relationship between intracranial pressure (ICP), ocular blood flow and structural optic nerve parameters. Materials and Methods: A prospective clinical study was conducted involving 24 patients with open-angle glaucoma and 25 healthy controls. Routine clinical examination was performed. Swept-source optical coherence tomography (SS-OCT) and OCT angiography (OCTA) images were taken (DRI-OCT Triton, Topcon). The vessel density (VD) values of the ONH were calculated around the optic nerve head (ONH). An orbital Doppler device (Vittamed 205, Kaunas, Lithuania) was used for non-invasive ICP measurements. Color Doppler imaging (CDI) (Mindray M7, Shenzhen, China) was used for retrobulbar blood flow measurements in the ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (SPCAs). Results: ICP was 8.35 ± 2.8 mmHg in the glaucoma group and 8.45 ± 3.19 mmHg in the control group (p = 0.907). In the glaucoma group, the VD of the superficial vascular plexus in the inferior-nasal (NI) sector of the ONH showed a correlation with ICP (r = 0.451, p = 0.05). In contrast, the control group exhibited weaker correlations. CRA peak systolic velocity (PSV) demonstrated significant moderate correlations with VD in multiple retinal layers, including the avascular retina layer in the temporal (T) sector (r = 0.637, p = 0.001). Conclusions: Lower ICP was significantly associated with the lower VD of the superficial plexus layer in the inferior-nasal sector in the glaucoma group, with the control group exhibiting weaker correlations in all sectors. Further longitudinal studies with larger sample sizes are needed to establish associations between intracranial pressure, ocular blood flow and ONH parameters. Full article

(This article belongs to the Special Issue Clinical Update on Optic Nerve Disorders)

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9 pages, 731 KB

Open AccessEditor’s ChoiceReview

Rho-Kinase Inhibitors in the Management of Fuchs Endothelial Corneal Dystrophy: A Review

by Anđela Jukić, Ana Pupić Bakrač, Biljana Đapic Ivančić, Andrijana Kopić, Ana Meter, Rajka Kasalica Žužul, Josip Pavan and Tomislav Jukić

Medicina 2025, 61(5), 772; https://doi.org/10.3390/medicina61050772 - 22 Apr 2025

Cited by 3 | Viewed by 4330

Abstract

Fuchs endothelial corneal dystrophy (FECD) is the most common corneal endothelial dystrophy. It is characterized by the progressive loss of corneal endothelial cells (CECs), guttae formation on the Descemet membrane, and corneal edema, leading to visual impairment. Corneal transplantation remains the standard treatment, [...] Read more.

Fuchs endothelial corneal dystrophy (FECD) is the most common corneal endothelial dystrophy. It is characterized by the progressive loss of corneal endothelial cells (CECs), guttae formation on the Descemet membrane, and corneal edema, leading to visual impairment. Corneal transplantation remains the standard treatment, but it has limitations such as donor shortages, infection risk, and graft rejection. Rho-kinase (ROCK) inhibitors have emerged as a promising pharmacological alternative. These agents promote CEC proliferation, migration, and adhesion while inhibiting apoptosis and enhancing corneal endothelial wound healing. Several studies have demonstrated the efficacy of ROCK inhibitors in improving corneal clarity and endothelial function, particularly when used as an adjunct to Descemet Stripping Only (DSO) surgery. Additionally, they show potential in preventing corneal edema in FECD patients undergoing cataract surgery. The methodology involved a literature search through the PubMed and Medline databases using relevant keywords. Only peer-reviewed articles in English were included, with additional references from selected articles reviewed to ensure comprehensive coverage. ROCK inhibitors offer a novel pharmacological approach to managing FECD. They have shown potential in promoting endothelial cell regeneration and improving corneal functIion. Despite promising results, further research is required to determine ROCK inhibitors’ long-term safety, optimal dosing, and efficacy in surgical and non-surgical FECD patients. Their potential to delay or prevent corneal transplantation represents a significant advancement in FECD management. Full article

(This article belongs to the Special Issue Advances in Corneal Management)

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22 pages, 8782 KB

Open AccessEditor’s ChoiceArticle

Anatomical Variables of the Superior Thyroid Artery on Computed Tomography Angiograms

by Rodica Narcisa Calotă, Mugurel Constantin Rusu, Marius Ioan Rusu, Cătălin Constantin Dumitru and Alexandra Diana Vrapciu

Medicina 2025, 61(5), 775; https://doi.org/10.3390/medicina61050775 - 22 Apr 2025

Cited by 4 | Viewed by 1794

Abstract

Background and Objectives: The superior thyroid artery (STA) typically has its origin inferiorly to the greater hyoid horn (GHHB) either from the external carotid artery (ECA) or from the carotid bifurcation (CB) or the common carotid artery (CCA). We aimed to determine [...] Read more.

Background and Objectives: The superior thyroid artery (STA) typically has its origin inferiorly to the greater hyoid horn (GHHB) either from the external carotid artery (ECA) or from the carotid bifurcation (CB) or the common carotid artery (CCA). We aimed to determine the topographic variants of the STA related to the GHHB and the artery of origin and to check their bilateral symmetry. Materials and Methods: Determinations were performed in a sample of 85 archived angio CT adult cases, comprising 53 men and 32 women. The origins of the STAs from the CCA/CB/ECA were classified as types A–C. We defined the vertical topographies of the STA as follows in relation to the GHHB: type 1 (infrahyoid), type 2 (hyoid), and type 3 (suprahyoid). Subtypes of the STA course were added: “a”, lateral to the GHHB; “b”, medial; and “c”, posterior to it. Unilateral combinations of types and bilateral associations of these were established. Results: In 170 carotid axes, we detected STA type A in 8.82%, type B in 28.82%, and type C in 60% of cases. It was absent in 2.35% of the cases. The infrahyoid type 1 of STA was found in 47.06% of cases. The hyoid type 2 was found in 20.59% (2a), 0.59% (2b), and 4.71% (2c). The suprahyoid type 3 was found in 21.18% (3a), 0% (3b), and 3.53% (3c). Thirteen unilateral combinations of types were found. The most prevalent ones were C1 (27.71%), C3a (17.47%), and B1 (15.66%). We established thirty-seven bilateral associations of unilateral combinations of types. The cases with asymmetrical bilateral associations of unilateral combinations of types prevailed. A lowered hyoid bone overlapping the thyroid cartilage was found in one of these cases. The prevailing associations were C1-C1 (bilateral infrahyoid origin of the STA from the ECA, 13/85, 15.29%), C3a-C3a (suprahyoid origins of the STAs from the ECAs and lateral courses over the GHHB, 9/85, 10.58%) and C1-B1 (infrahyoid origins from the ECA and CB, 8/85, 9.41%). Conclusions: The vertical topography of the STA is highly variable and hardly predictable but can be examined in imaging studies. The GHHB may be of use to identify and manage the artery. The STA is rarely absent. Full article

(This article belongs to the Section Endocrinology)

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11 pages, 288 KB

Open AccessEditor’s ChoiceArticle

Correlation and Comparative Evaluation of MOCART and MOCART 2.0 for Assessing Cartilage Repair

by Felix Conrad Oettl, Louis Leuthard, Moritz Brunner, Vincent A. Stadelmann, Stefan Preiss, Michael Leunig, Gian M. Salzmann and Jakob Hax

Medicina 2025, 61(4), 745; https://doi.org/10.3390/medicina61040745 - 18 Apr 2025

Cited by 1 | Viewed by 2129

Abstract

Background and Objectives: Chondral and osteochondral lesions can lead to osteoarthritis if untreated, making accurate assessment of cartilage repair outcomes essential for optimizing treatment strategies. The objective of this study was to compare MOCART and MOCART 2.0 and to evaluate the clinical [...] Read more.

Background and Objectives: Chondral and osteochondral lesions can lead to osteoarthritis if untreated, making accurate assessment of cartilage repair outcomes essential for optimizing treatment strategies. The objective of this study was to compare MOCART and MOCART 2.0 and to evaluate the clinical utility of both across different surgical cartilage repair techniques and various time points. Material and Methods: This study included 111 patients (age: 35 ± 10, 35% female) who underwent cartilage repair surgery of the knee between September 2015 and March 2022. A total of 188 postoperative magnetic resonance images were evaluated using MOCART and MOCART 2.0. The correlations between both scores, as well as to the change in Patient-Reported Outcome Measures (PROMs), were determined. Results: MOCART 2.0 scores (66 ± 13) were significantly higher than MOCART scores (58 ± 13, p < 0.001). Positive correlation was observed between scoring systems (r = 0.837, p < 0.001). There was no significant correlation between MOCART or MOCART 2.0 scores and the change in PROMs. Noticeably, there was a statistically significant correlation between both MOCART and MOCART 2.0 in the AutoCart subgroup across multiple timepoints for the change in PROMs. Conclusions: Based on radiographic–clinical outcome discordance, clinicians should not rely solely on MOCART or MOCART 2.0 scores when evaluating cartilage repair success but instead prioritize patient-reported functional improvements while using imaging as a complementary assessment tool. Full article

(This article belongs to the Section Sports Medicine and Sports Traumatology)

12 pages, 3749 KB

Open AccessEditor’s ChoiceArticle

3D CT-Based Preoperative Planning and Intraoperative Navigation in Reverse Shoulder Arthroplasty: Early Clinical Outcomes

by Elisa Troiano, Azzurra Masini, Giovanni Battista Colasanti, Caterina Drago, Stefano Giannotti and Nicola Mondanelli

Medicina 2025, 61(4), 749; https://doi.org/10.3390/medicina61040749 - 18 Apr 2025

Cited by 5 | Viewed by 2382

Abstract

Background and Objectives: Reverse shoulder arthroplasty (RSA) is an effective surgical procedure for treating end-stage rotator cuff arthropathy, but it is burdened by a relatively high complication rate, mainly due to glenoid component failure. Preoperative planning and intraoperative navigation based on three-dimensional [...] Read more.

Background and Objectives: Reverse shoulder arthroplasty (RSA) is an effective surgical procedure for treating end-stage rotator cuff arthropathy, but it is burdened by a relatively high complication rate, mainly due to glenoid component failure. Preoperative planning and intraoperative navigation based on three-dimensional computed tomography (3D CT) scans have proven to be efficient tools for improving the accuracy and stability of the glenoid component. However, this technology is still developing, and there is currently little available research on the subject, especially where clinical outcomes are concerned. The purpose of this retrospective observational study is to report the radiographic and clinical outcomes of a consecutive series of patients that underwent RSA with the use of these new technologies, compared to a standard procedure. Materials and Methods: A consecutive series of 80 patients underwent RSA for shoulder osteoarthritis by a single surgeon at a single institution with a mean follow-up of 41.9 ± 23.6 months (range 24–108) and were divided into two groups according to the surgical technique employed (conventional or navigated surgery), and they were clinically and radiographically assessed at 1, 3, 6, and 12 months after surgery, and then annually. Results: No statistically significant differences were highlighted among the two groups according to complication rate, radiographical glenoid notching, and clinical outcomes. However, a statistically significant difference was observed in screw number and length and surgical time. In the navigated group, fewer screws with longer lengths had been implanted, with a longer surgical time. Conclusions: The use of 3D CT-based preoperative planning and intraoperative navigation is a safe procedure and produces comparable results with respect to standard instrumentation, without an increased risk of complications. It allowed to achieve higher stability of the implant, saving bone stock due to the use of fewer and longer screws than in a conventional procedure. This could also eventually result in a higher longevity of the implant itself. Full article

(This article belongs to the Special Issue Cutting-Edge Topics in Joint Arthroplasties)

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16 pages, 1021 KB

Open AccessEditor’s ChoiceReview

Use of Artificial Intelligence on Imaging and Preoperatory Planning of the Knee Joint: A Scoping Review

by Luca Bertolino, Marta Bianca Maria Ranzini, Alberto Favaro, Elena Bardi, Flavio Lorenzo Ronzoni and Tommaso Bonanzinga

Medicina 2025, 61(4), 737; https://doi.org/10.3390/medicina61040737 - 16 Apr 2025

Cited by 7 | Viewed by 3264

Abstract

Background and Objectives: This scoping review explores the current state of the art of AI-based applications in the field of orthopedics, focusing on its implementation in diagnostic imaging and preoperative planning of knee joint procedures. Materials and Methods: The search was [...] Read more.

Background and Objectives: This scoping review explores the current state of the art of AI-based applications in the field of orthopedics, focusing on its implementation in diagnostic imaging and preoperative planning of knee joint procedures. Materials and Methods: The search was carried out using the recognized scholarly databases PubMed, Medline and Embase and was set to identify original research addressing AI applied to imaging in knee diagnosis and surgical planning, written in English and published up to January 2025. Results: The search produced 1612 papers, of which 36 were included in our review. All papers addressed AI applied to common imaging methods in clinical practice. Of these, thirty integrated AI-based tools with X-rays, one applied AI to X-rays to produce CT-like 3D reproductions, and two studies applied AI to MRI. Conclusions: Several AI tools have already been validated for enhancing the accuracy of measurements and detecting additional parameters in a shorter time compared to standard assessments. We expect these may soon be introduced into routine clinical practice to streamline a number of technical tasks and in some cases to replace the need for human intervention. Full article

(This article belongs to the Section Orthopedics)

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12 pages, 3256 KB

Open AccessEditor’s ChoiceArticle

Prognostic Impact of Klintrup–Mäkinen (KM) Score in Gastric Cancer and Its Association with Pathological Parameters

by Andreea-Raluca Cozac-Szőke, Georgian-Nicolae Radu, Anca Negovan, Dan Alexandru Cozac, Sabin Turdean, Andreea-Cătălina Tinca, Emőke-Andrea Szász, Iuliu-Gabriel Cocuz, Adrian-Horațiu Sabău, Raluca Niculescu, Diana Maria Chiorean, Alexandru Nicușor Tomuț and Ovidiu Simion Cotoi

Medicina 2025, 61(4), 715; https://doi.org/10.3390/medicina61040715 - 13 Apr 2025

Cited by 2 | Viewed by 1529

Abstract

Background and Objectives: Gastric cancer (GC) remains a significant global health challenge with a poor prognosis. This study aimed to evaluate the association between Klintrup–Mäkinen (KM) inflammatory infiltrate grading and clinicopathological features in gastric cancer patients, investigating its potential as a prognostic marker. [...] Read more.

Background and Objectives: Gastric cancer (GC) remains a significant global health challenge with a poor prognosis. This study aimed to evaluate the association between Klintrup–Mäkinen (KM) inflammatory infiltrate grading and clinicopathological features in gastric cancer patients, investigating its potential as a prognostic marker. Material and Methods: This retrospective study analyzed 133 gastric adenocarcinoma patients diagnosed between 2020 and 2021 at County Clinical Hospital in Târgu Mureș, Romania. Patients were divided into two groups based on KM grades: low (grades 0–1, n = 62) and high (grades 2–3, n = 71). Clinicopathological characteristics and survival outcomes were compared between the groups. Results: Demographic characteristics were similar between the groups. Patients with low KM grades demonstrated significantly more aggressive tumor features, including a higher prevalence of Borrmann classification types III-IV (75.8% vs. 54.9%, p = 0.01), poorly differentiated histology (74.1% vs. 33.8%, p < 0.0001), advanced T stage (93.5% vs. 80.2%, p = 0.04), and lymph node involvement (87% vs. 60.5%, p = 0.0008). This group also exhibited higher rates of lymphatic invasion (79% vs. 50.7%, p = 0.001), venous invasion (51.6% vs. 30.9%, p = 0.02), perineural invasion (50% vs. 22.5%, p = 0.001), and positive surgical margins (32.2% vs. 15.4%, p = 0.02). Survival analysis revealed a hazard ratio of 1.642 (95% CI: 1.02–2.62) for patients with low KM grades compared to those with high KM grades. Conclusions: Low KM grades are associated with more aggressive tumor characteristics and poorer prognosis in GC patients. The KM score may serve as a valuable, cost-effective histological marker for assessing tumor aggressiveness and could aid in risk stratification when applied to routine H&E-stained slides. While it does not replace immunohistochemical or molecular analyses, integrating the KM score into pathological assessment may enhance prognostic accuracy and support identifying patients who might benefit from immunotherapy. Full article

(This article belongs to the Special Issue Towards Improved Cancer Diagnosis: New Developments in Histopathology)

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15 pages, 1348 KB

Open AccessEditor’s ChoiceReview

New Frontiers in Nutritional and Therapeutic Interventions for Obesity Phenotypes

by Angelo Maria Patti, Rosaria Vincenza Giglio, Marcello Ciaccio, Anca Pantea Stoian, Teodor Salmen, Ioana-Cristina Bica, Imran Rangraze, Mohamed El Tanani, Manfredi Rizzo and Ali Abbas Rizvi

Medicina 2025, 61(4), 664; https://doi.org/10.3390/medicina61040664 - 3 Apr 2025

Cited by 5 | Viewed by 5914

Abstract

The heterogeneity among patients with obesity is particularly evident in the weight loss response to interventions such as diets, drugs, devices and surgery. Obesity can be “catalogued” into four phenotypes: hungry brain (abnormal satiety for alteration of gut–brain axis), emotional hunger (hedonic eating), [...] Read more.

The heterogeneity among patients with obesity is particularly evident in the weight loss response to interventions such as diets, drugs, devices and surgery. Obesity can be “catalogued” into four phenotypes: hungry brain (abnormal satiety for alteration of gut–brain axis), emotional hunger (hedonic eating), hungry gut (abnormal duration of satiety for faster gastric emptying) and slow burning (slowing of the metabolic rate). Phenotypes are grafted onto this complexity, the recognition of which allows for personalized medicine and increasingly targeted therapies. Although there are no standardized treatment protocols, we present management options consisting of lifestyle modifications and pharmacologic therapies. Nutritional advice and encouragement of adequate physical activity lead to increased self-efficacy and promote a sense of well-being when coupled with psychological approaches involving mindful eating. In summary, obesity has a complex pathophysiology best addressed through a therapeutic process suited to the phenotype encountered and in synergy with multifactorial interventions. Full article

(This article belongs to the Section Endocrinology)

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16 pages, 2481 KB

Open AccessEditor’s ChoiceReview

Quercetin as a Potential Therapeutic Agent for Malignant Melanoma—A Review of Current Evidence and Future Directions

by Teodora Hoinoiu, Victor Dumitrascu, Daniel Pit, David-Alexandru Schipor, Madalina Jabri-Tabrizi, Bogdan Hoinoiu, David Emanuel Petreuș and Corina Seiman

Medicina 2025, 61(4), 656; https://doi.org/10.3390/medicina61040656 - 2 Apr 2025

Cited by 6 | Viewed by 3062

Abstract

Neoplastic disorders, particularly malignant carcinomas, are complex systemic diseases characterized by unregulated cellular proliferation, the invasion of adjacent tissues, and potential metastasis to distant bodily sites. Among the diverse spectrum of cancer subtypes, malignant melanoma is a highly aggressive form of cutaneous cancer [...] Read more.

Neoplastic disorders, particularly malignant carcinomas, are complex systemic diseases characterized by unregulated cellular proliferation, the invasion of adjacent tissues, and potential metastasis to distant bodily sites. Among the diverse spectrum of cancer subtypes, malignant melanoma is a highly aggressive form of cutaneous cancer originating in melanocytes, the pigment-producing cells resident in the skin. This malignancy is distinguished by its rapid and uncontrolled growth, as well as its propensity for metastasis to vital organs, thereby posing significant challenges to therapeutic intervention and prognostication. Early detection of melanoma is crucial for optimizing patient outcomes, as diagnosis at an advanced stage often yields a poor prognosis and limited treatment options. Diagnostic modalities for melanoma encompass comprehensive clinical evaluations by dermatologists; radiological imaging techniques such as ultrasonography, magnetic resonance imaging (MRI), computed tomography (CT) scans; and excisional biopsies for accurate histopathological assessment. Malignant melanoma is typically treated with surgery to remove the tumor, followed by immunotherapy to enhance the immune response, targeted therapy for tumors with specific genetic mutations, chemotherapy for advanced stages, radiation therapy to manage metastasis, and other adjunct therapies. This review presents the properties and possible adjunct therapeutic effects against malignant melanoma of quercetin found in the literature and explores, based on the observed physicochemical properties and biological activity, its potential development as a topical formulation for cutaneous application. Quercetin is a naturally occurring flavonoid compound abundant in various plant-based food sources, including apples, onions, berries, and citrus fruits, and has exhibited promising antiproliferative, antioxidant, and anticancer properties. Its distinctive biochemical structure enables quercetin to effectively neutralize reactive oxygen species and modulate key carcinogenic pathways, thereby rendering it a potential candidate for therapeutic intervention in managing malignant tumors, including melanoma. Full article

(This article belongs to the Special Issue Advances in the Diagnosis, Prevention and Treatment of Skin Tumors)

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16 pages, 2318 KB

Open AccessEditor’s ChoiceReview

HER2-Low Breast Cancer—Current Knowledge and Future Directions

by Abeer M. Shaaban, Tanvier Kaur and Elena Provenzano

Medicina 2025, 61(4), 644; https://doi.org/10.3390/medicina61040644 - 1 Apr 2025

Cited by 8 | Viewed by 7375

Abstract

The concept of binary classification of HER2 status has recently been challenged following the DESTINY-Breast trial data showing a clinically meaningful response to antibody–drug conjugates (ADCs) in invasive breast cancer expressing low levels of HER2. HER2-low breast cancer is defined as an immunohistochemistry [...] Read more.

The concept of binary classification of HER2 status has recently been challenged following the DESTINY-Breast trial data showing a clinically meaningful response to antibody–drug conjugates (ADCs) in invasive breast cancer expressing low levels of HER2. HER2-low breast cancer is defined as an immunohistochemistry (IHC) score of 1+ and 2+ without HER2 gene amplification. While HER2-low breast cancer does not represent a biological entity, it encompasses both hormone receptor-positive and triple-negative breast cancer. Differences exist between this group and HER2-null breast cancer. In this review, we provide an update on HER2-low and HER2-ultralow breast cancer, including background trial data, the evolution of HER2-low expression, current clinical guidelines, quality issues, and future directions. Full article

(This article belongs to the Special Issue Future Trends in Breast Cancer Management)

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17 pages, 2671 KB

Open AccessEditor’s ChoiceArticle

Effects of Physical Exercise on Walking Distance and Functional Limitations in Patients with Chronic Dyspnea

by Kinga Vindis, Noemi Nemeth, Cristian Marge, Carmen Pantis, Mircea Gheorghe Pop, Manuela Simona Pop, Laura Ioana Bondar, Maria Carolina Jurcau and Katalin Babeș

Medicina 2025, 61(4), 636; https://doi.org/10.3390/medicina61040636 - 30 Mar 2025

Cited by 3 | Viewed by 2802

Abstract

Background and Objectives: Chronic dyspnea is a common clinical manifestation in patients suffering from cardiovascular and respiratory diseases globally, representing an independent predictor of mortality for these patients. In addition, it may be a symptom associated with other conditions such as anemia, [...] Read more.

Background and Objectives: Chronic dyspnea is a common clinical manifestation in patients suffering from cardiovascular and respiratory diseases globally, representing an independent predictor of mortality for these patients. In addition, it may be a symptom associated with other conditions such as anemia, physical deconditioning, or anxiety. Methods: A prospective study was conducted, between 1 January 2021 and 30 June 2022, at the Medical Recovery Section from “Dr. Pop Mircea Municipal Hospital Pop Mircea” in Marghita. A total of 163 consecutive patients with chronic dyspnea of various etiologies were evaluated for inclusion in the study. Patients who met the inclusion criteria followed a personalized physical training program of variable duration (between 20 and 40 min) up to the limit of exercise tolerance (grade 3–4 modified Borg scale or up to 70% of maximum heart rate, calculated with the formula 220 age in years); the first 10 days, the training was supervised by a physiotherapist, then patients followed a program of 30 min of exercise 5 days/week at home for 3 months. Assessments, performed at inclusion and after 3 months of training, consisted of the 6 min walk test (6MWT) and the London Chest Activity of Daily Living (LCADL) scale. Results: Pulmonary etiology is the most common cause of dyspnea in the cohort (61.65%). The number of patients without ventilatory defects is 56, or 38.35%. The mean value of initial functional limitation (LCADL1) improved significantly after 3 months (LACDL2) of rehabilitation treatment (38% versus 26.5%); at the same time, the mean walking distance (6MWT) increased by 76 m. Conclusions: An adequate rehabilitation program and sedentary lifestyle change significantly reduce the functional limitation of the patient with chronic dyspnea and increase walking distance. Predictors for 6MWT gait test are age, LCADL score, dyspnea level, and cardiac etiology of chronic dyspnea. Full article

(This article belongs to the Section Sports Medicine and Sports Traumatology)

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16 pages, 324 KB

Open AccessEditor’s ChoiceReview

New and Emerging Biologics and Jak Inhibitors for the Treatment of Prurigo Nodularis: A Narrative Review

by Matteo Bianco, Francesco D’Oria, Costanza Falcidia, Giulio Foggi, Elena Matteodo, Sara Di Giulio, Paola Facheris, Luciano Ibba, Chiara Perugini, Mario Valenti, Carlo Alberto Vignoli, Antonio Costanzo, Alessandra Narcisi and Luigi Gargiulo

Medicina 2025, 61(4), 631; https://doi.org/10.3390/medicina61040631 - 29 Mar 2025

Cited by 7 | Viewed by 6287

Abstract

Prurigo nodularis (PN) is a chronic dermatological condition characterized by intensely pruritic nodules resulting from repeated scratching. Its pathogenesis involves neuroimmune dysregulation, inflammatory cytokines, and neural proliferation. Conventional treatments often provide limited relief, necessitating novel therapeutic approaches. This narrative review explores emerging biologics [...] Read more.

Prurigo nodularis (PN) is a chronic dermatological condition characterized by intensely pruritic nodules resulting from repeated scratching. Its pathogenesis involves neuroimmune dysregulation, inflammatory cytokines, and neural proliferation. Conventional treatments often provide limited relief, necessitating novel therapeutic approaches. This narrative review explores emerging biologics and small molecules for PN treatment, assessing their mechanisms, efficacy, and safety. A comprehensive literature search was conducted using PubMed, Google Scholar, and Web of Science for relevant studies up to February 2025. Additionally, ongoing clinical trials were identified through a verified international website. The search terms included “prurigo nodularis”, “biologic treatments”, “monoclonal antibodies”, “small molecules”, and “JAK inhibitors”. Among new treatment options, dupilumab, an IL-4 receptor antagonist, and nemolizumab, an IL-31 receptor inhibitor, demonstrated significant efficacy in reducing pruritus and lesion severity in PN patients. Other promising monoclonal antibodies include vixarelimab (OSMRβ inhibitor) and barzolvolimab (KIT inhibitor). Small molecules such as JAK inhibitors (upadacitinib, povorcitinib) also show potential by modulating inflammatory pathways. Clinical trials highlight their efficacy, safety, and long-term benefits. Emerging biologics and small molecules represent a transformative approach for PN management, offering targeted therapies that address underlying immunological and neurological mechanisms. Ongoing research and long-term studies are crucial to optimizing treatment strategies and improving patient outcomes. Full article

(This article belongs to the Special Issue Chronic Inflammatory Skin Diseases: Where We Are and Where We Are Going: 2nd Edition)

12 pages, 1798 KB

Open AccessEditor’s ChoiceSystematic Review

Atherogenic Index of Plasma in Metabolic Syndrome—A Systematic Review and Meta-Analysis

by Leia Mossane Andraschko, Gabi Gazi, Daniel-Corneliu Leucuta, Stefan-Lucian Popa, Bogdan Augustin Chis and Abdulrahman Ismaiel

Medicina 2025, 61(4), 611; https://doi.org/10.3390/medicina61040611 - 27 Mar 2025

Cited by 9 | Viewed by 3835

Abstract

Background and Objectives: Numerous studies have explored the biomarker atherogenic index of plasma (AIP) in relation to metabolic syndrome (MetS), showing its potential utility in assessing this condition. However, the existing evidence remains inconsistent and inconclusive. Therefore, this study aimed to evaluate [...] Read more.

Background and Objectives: Numerous studies have explored the biomarker atherogenic index of plasma (AIP) in relation to metabolic syndrome (MetS), showing its potential utility in assessing this condition. However, the existing evidence remains inconsistent and inconclusive. Therefore, this study aimed to evaluate the association between AIP and MetS and assess its predictive accuracy. Materials and Methods: A comprehensive search of PubMed, EMBASE, and Scopus was conducted using a predefined search strategy to identify relevant studies. Eligible studies diagnosed MetS based on the International Diabetes Federation criteria. The primary outcomes were the mean difference (MD) in AIP between MetS patients and healthy controls, as well as the area under the curve (AUC) for AIP in predicting MetS. Results: Thirteen studies involving 17,689 participants met the inclusion criteria and were included in the systematic review and meta-analysis. AIP levels were significantly higher in MetS patients compared to healthy controls, with an MD of 0.309 (95% CI 0.214, 0.405). In contrast, the difference in AIP levels between type 2 diabetes mellitus (T2DM) patients with MetS and normoglycemic MetS patients was not statistically significant (MD 0.142, 95% CI −0.091, 0.376). The predictive accuracy of AIP for MetS yielded an AUC of 0.864 (95% CI 0.856, 0.871). Conclusions: AIP levels are significantly elevated in MetS patients compared to healthy individuals, supporting AIP’s potential role as a biomarker for MetS. However, AIP levels did not differ significantly between T2DM patients with MetS and normoglycemic MetS patients. The predictive accuracy of AIP for MetS is acceptable, indicating that AIP may serve as a useful tool in MetS diagnosis. Further research is warranted to clarify its diagnostic and prognostic significance in clinical settings. Full article

(This article belongs to the Special Issue Epidemiology of Autiommune and Metabolic Diseases)

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15 pages, 966 KB

Open AccessEditor’s ChoiceReview

Immunosuppressive Therapy for Usual Interstitial Pneumonia in Autoimmune Rheumatic Diseases: A Review

by Domenico Sambataro, Giulia Morina, Alessandro Libra, Stefano Palmucci, Francesco Pallotti, Giulio Geraci, Gaetano La Rocca, Francesco Ferro, Michele Moretti, Chiara Baldini, Carlo Vancheri and Gianluca Sambataro

Medicina 2025, 61(4), 599; https://doi.org/10.3390/medicina61040599 - 26 Mar 2025

Cited by 3 | Viewed by 3683

Abstract

Usual Interstitial Pneumonia (UIP) is the most severe radiological/histological pattern of Interstitial Lung Disease (ILD). It is typical of Idiopathic Pulmonary Fibrosis (IPF), but is also frequently described in Autoimmune Rheumatic Diseases (ARDs), sharing with IPF common risk factors, genetic backgrounds, and in [...] Read more.

Usual Interstitial Pneumonia (UIP) is the most severe radiological/histological pattern of Interstitial Lung Disease (ILD). It is typical of Idiopathic Pulmonary Fibrosis (IPF), but is also frequently described in Autoimmune Rheumatic Diseases (ARDs), sharing with IPF common risk factors, genetic backgrounds, and in some cases, disease progression and prognosis. Following the results of the PANTHER study, immunosuppressive drugs are now not recommended for the treatment of IPF; however, their use for the treatment of UIP secondary to ARDs is still under debate. The aim of this review is to summarize existing knowledge on the clinical presentation of autoimmune UIP and its treatment with immunosuppressive drugs. We searched PubMed for English language clinical trials and studies on treatment of ARDs-ILD, looking for specific treatments of UIP-ARDs. The available clinical trials rarely stratify patients by ILD pattern, and clinical studies generally lack a comparison with a placebo group. In Systemic Sclerosis, UIP patients showed a non-significant trend of worsening under immunosuppression. On the contrary, in Interstitial Pneumonia with Autoimmune Features and, above all, Rheumatoid Arthritis, immunosuppressive treatment produced promising results in the management of UIP patients. In conclusion, the current evidence about the immunosuppressive treatment of UIP-ARDs is limited and conflicting. There is an urgent need to adequately assess this topic with specific clinical trials, as has already been performed for IPF. The possibility should be considered that different ARDs can respond differently to immunosuppression. Finally, a wider use of histological samples could produce valuable information from a diagnostic, therapeutic, and research point of view. Full article

(This article belongs to the Section Pulmonology)

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10 pages, 3278 KB

Open AccessEditor’s ChoiceArticle

Augmented Reality in Scoliosis Correction Surgery: Efficiency and Accuracy in Pedicle Screw Instrumentation

by Chia-Ning Chang, Chi-Ruei Li, Sian-Siang Liao, Chiung-Chyi Shen, Kai-Yuan Chen, Chung-Hsin Lee and Meng-Yin Yang

Medicina 2025, 61(4), 576; https://doi.org/10.3390/medicina61040576 - 24 Mar 2025

Cited by 3 | Viewed by 2294

Abstract

Background and Objectives: Recent advancements in spinal navigation methodologies, particularly augmented reality (AR) techniques, have significantly enhanced the precision of spinal instrumentation procedures. This study aimed to evaluate the efficacy of AR-assisted navigation in spinal instrumentation surgery for thoracolumbar scoliosis. Materials and [...] Read more.

Background and Objectives: Recent advancements in spinal navigation methodologies, particularly augmented reality (AR) techniques, have significantly enhanced the precision of spinal instrumentation procedures. This study aimed to evaluate the efficacy of AR-assisted navigation in spinal instrumentation surgery for thoracolumbar scoliosis. Materials and Methods: This retrospective observational study included 10 patients with thoracolumbar scoliosis who met specific inclusion criteria and were recruited at a single medical center. Two neurosurgeons and one neuroradiologist used the Gertzbein–Robbins scale (GRS) for radiological evaluation. Preoperative and postoperative Cobb angles were measured to assess the correction of scoliosis. Overall, 257 screws were placed using the AR-assisted navigation system during thoracic and lumbar spinal deformity surgeries. Results: Among the 257 screws, 197 were placed in the thoracic spine and 60 in the lumbar spine, achieving an overall instrumentation accuracy of 98%. The preoperative Cobb angle of 69.5 ± 22.2° significantly improved to 10.1 ± 4.1° postoperatively. Regarding first-attempt screw placement accuracy, 97.4% of the screws in the thoracic spine (graded as GRS A or B) and 100% in the lumbar spine were placed with precision. Five grade C thoracic screws were identified, one of which required re-instrumentation. Conclusions: The AR navigation technique substantially improved the precision of spinal deformity surgery, with a high screw placement accuracy rate and significant scoliosis correction. The benefits of reduced attention diversion and an intuitive surgical experience suggest that AR technology could significantly improve spinal surgery practices and training programs, indicating potential for broader applicability in the future. Full article

(This article belongs to the Special Issue New Frontiers in Spine Surgery and Spine Disorders)

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12 pages, 1611 KB

Open AccessEditor’s ChoiceArticle

Non-Invasive Monitoring of Intracranial Pressure Pulse Waves from Closed Eyelids in Patients with Normal-Tension Glaucoma

by Laimonas Bartusis, Solventa Krakauskaite, Ugne Kevalaite, Austeja Judickaite, Arminas Zizas, Akvile Stoskuviene, Edvinas Chaleckas, Mantas Deimantavicius, Yasin Hamarat, Fabien Scalzo, Kristina Berskiene, Ingrida Januleviciene and Arminas Ragauskas

Medicina 2025, 61(4), 566; https://doi.org/10.3390/medicina61040566 - 22 Mar 2025

Cited by 2 | Viewed by 1567

Abstract

Background and Objectives: Normal-tension glaucoma (NTG) is a subtype of primary open-angle glaucoma characterized by progressive optic nerve damage despite intraocular pressure (IOP) remaining within the normal range. The underlying pathophysiology of NTG remains incompletely understood, and its diagnosis is often delayed [...] Read more.

Background and Objectives: Normal-tension glaucoma (NTG) is a subtype of primary open-angle glaucoma characterized by progressive optic nerve damage despite intraocular pressure (IOP) remaining within the normal range. The underlying pathophysiology of NTG remains incompletely understood, and its diagnosis is often delayed due to the lack of a definitive screening tool. This study aimed to evaluate differences in intracranial pressure pulse wave amplitude recorded from closed eyelids between NTG patients and control subjects using a novel non-invasive monitoring technology. Materials and Methods: A cross-sectional observational study was conducted, enrolling NTG patients and age-matched controls. Intracranial pressure pulse wave signals were recorded from closed eyelids using the ’Archimedes’ 02 device, which employs a highly sensitive digital pressure sensor and hydromechanical coupling for signal transmission. The amplitude of recorded intracranial pressure pulse waves was analyzed and compared between groups. Statistical analyses were performed using IBM SPSS Statistics 30.0, with significance set at p < 0.05. Results: A total of 140 participants were enrolled, including 68 NTG patients and 72 controls. After applying exclusion criteria, 63 NTG patients and 68 controls were included in the final analysis. The median intracranial pressure pulse wave amplitude was significantly higher in NTG patients (0.1326 a.u.) than in controls (0.0889 a.u.), with p = 0.01. Conclusions: These findings suggest that intracranial pressure pulse wave monitoring may serve as a potential biomarker for NTG. Further studies are needed to determine the diagnostic accuracy, sensitivity, and specificity of this technology for NTG detection. Full article

(This article belongs to the Special Issue Ophthalmology: New Diagnostic and Treatment Approaches)

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19 pages, 5417 KB

Open AccessEditor’s ChoiceReview

Scar Management in Pediatric Patients

by Sydney Barone, Eric Bao, Stephanie Rothberg, Jose F. Palacios, Isabelle T. Smith, Neil Tanna and Nicholas Bastidas

Medicina 2025, 61(4), 553; https://doi.org/10.3390/medicina61040553 - 21 Mar 2025

Cited by 5 | Viewed by 11545

Abstract

Background and Objectives: Pediatric patients can acquire scars from both accidental injury and surgical procedures. While scars cannot be avoided if a full-thickness injury occurs, scar visibility may be minimized through a variety of approaches. In this narrative review, we evaluate the [...] Read more.

Background and Objectives: Pediatric patients can acquire scars from both accidental injury and surgical procedures. While scars cannot be avoided if a full-thickness injury occurs, scar visibility may be minimized through a variety of approaches. In this narrative review, we evaluate the current evidence and propose an algorithm for scar management in pediatric patients. Materials and Methods: A review of the literature was performed for scar management techniques for pediatric patients. Management modalities based on the type of scar and dosing, treatment regimen, and safety profiles are described in this article and used to create a scar management algorithm. Results: The initial step to scar management in the pediatric population involves ensuring minimal wound tension, which can be achieved through making the incision along relaxed skin tension lines, and early, minimal tension wound closure. Subsequent treatments to optimize scar care should begin 2–3 weeks following wound closure and involve the application of silicone gel or sheets and scar massaging. When topical products are insufficient, laser therapy can be utilized for the management of immature erythematous or thick scars. When mature, pathological scars form such as atrophic scars, hyperpigmentation, hypertrophic scars, or keloids, a combination of modalities is recommended. These modalities vary by scar type and include retinoids and dermabrasion for atrophic scars; retinoids, hydroquinone, and laser therapy for hyperpigmentation; and pressure therapy, corticosteroids, and laser therapy for hypertrophic scars and keloids. When mature, pathological scars persist following 12 months of non-invasive therapies, surgical excision should be considered. Conclusions: Several treatment options are available to manage scars in the pediatric population depending on scar type. Full article

(This article belongs to the Section Surgery)

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