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Advances in Minimally Invasive Esophagectomy—An Overview of Recent Developments and a Novel Classification of Innovations in Treatment of Thoracic Esophageal Cancer -
Oral Probiotics in Acne vulgaris: A Systematic Review and Meta-Analysis of Double-Blind Randomized Clinical Trials -
Clinical Characteristics, Microbiological Spectrum, Biomarkers, and Imaging Insights in Acute Pyelonephritis and Its Complicated Forms—A Systematic Review -
Early SGLT2 Inhibitor Therapy in Acute Coronary Syndrome: Mitigating Adverse Remodeling in High-Risk Phenotypes—A Real-World Study -
Stroke Neurorehabilitation and the Role of Motor Imagery Training: Do ARAT and Barthel Index Improvements Support Its Clinical Use? A Systematic Review and Meta-Analysis
Journal Description
Medicina
Medicina
is an international, peer-reviewed, open access journal covering all problems related to medicine, published monthly online. It is the official journal of the Lithuanian University of Health Sciences (LUHS). The Lithuanian Medical Association (LMA), Vilnius University, Rīga Stradiņš University, University of Latvia, and University of Tartu are affiliated with Medicina, serving as their official journal. Members of these organizations receive discounts on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, and other databases.
- Journal Rank: JCR - Q1 (Medicine, General and Internal) / CiteScore - Q1 (General Medicine)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 17.5 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the second half of 2025).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
2.4 (2024);
5-Year Impact Factor:
2.8 (2024)
Latest Articles
Early Prognostic Factors in Multiple Sclerosis: Clinical and Therapeutic Implications
Medicina 2026, 62(3), 475; https://doi.org/10.3390/medicina62030475 - 2 Mar 2026
Abstract
Introduction: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system with a highly heterogeneous clinical course. Early identification of patients at risk of aggressive disease progression is crucial for optimizing therapeutic strategies, including eligibility for highly effective
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Introduction: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system with a highly heterogeneous clinical course. Early identification of patients at risk of aggressive disease progression is crucial for optimizing therapeutic strategies, including eligibility for highly effective treatments. Objective: The aim of this review was to synthesize current data on prognostic factors in multiple sclerosis, with particular emphasis on their significance in the early stages of the disease and potential clinical implications. Methods: A narrative systematic review of the literature was conducted, including observational studies, cohort studies, meta-analyses, and systematic reviews on the natural course of MS, prognostic factors, and clinical, neuroimaging, and laboratory biomarkers. We comprehensively reviewed PubMed and Scopus databases, focusing on English-language publications. Study selection prioritized longitudinal studies and meta-analyses with clear outcome definitions and sufficient follow-up. Formal quality scoring was not applied due to the narrative design of the review. Results: Key adverse prognostic factors include older age at onset, polysymptomatic onset, high relapse activity in the first years, incomplete remission after relapses, and the primary progressive form. Magnetic resonance imaging features, including the number and location of T2 lesions, contrast activity, the presence of spinal cord lesions, PRLs and SELs, and severe brain atrophy, also have significant predictive value. Increasing importance is being attached to laboratory biomarkers, such as oligoclonal bands, light neurofilaments, free kappa light chains, and GFAP. Conclusions: An integrated assessment of clinical, neuroimaging, and laboratory factors enables more effective risk stratification in patients with newly diagnosed MS. Early identification of an unfavorable prognostic profile may provide a basis for individualizing treatment and considering the use of highly effective therapies early in the course of the disease.
Full article
(This article belongs to the Section Neurology)
Open AccessArticle
Relationship Between the Lactate-to-Albumin Ratio and Acute Kidney Injury in Patients with Pulmonary Embolism: A Retrospective Cohort Study
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Dogan Ilis, Ayca Arslan, Inanc Artac, Muammer Karakayali, Omer Kertmen, Hatice Taskan, Yuksel Erata, Ezgi Guzel, Yavuz Karabag and Ibrahim Rencuzogullari
Medicina 2026, 62(3), 474; https://doi.org/10.3390/medicina62030474 - 2 Mar 2026
Abstract
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Background and Objectives: Pulmonary embolism (PE), the third most prevalent cause of cardiovascular death, is often regarded as a potentially fatal condition. Renal function has been shown to affect the short- and long-term prognosis of acute PE in several large registries. Therefore,
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Background and Objectives: Pulmonary embolism (PE), the third most prevalent cause of cardiovascular death, is often regarded as a potentially fatal condition. Renal function has been shown to affect the short- and long-term prognosis of acute PE in several large registries. Therefore, the purpose of this study is to investigate the relationship between acute kidney injury (AKI) and the lactate-to-albumin ratio (LAR) in patients hospitalized for PE. Materials and Methods: 264 PE patients were included in this retrospective analysis. Based on the presence or absence of AKI, the study population was split into two groups. Results: Of the 264 patients included in our study, 161 (61%) were female. The median age was 67 ± 16 years. The sample was divided into two groups based on whether AKI developed (No AKI group, n = 176; AKI group, n = 88). A multivariate logistic regression analysis revealed that sPESI score, receiving fibrinolytic therapy (tPA), and LAR (OR: 6.334, 95% CI: 3.070–13.069; p < 0.001) were independently associated with AKI in patients with PE. In particular, an LAR > 0.55 predicted AKI in patients with PE, with a sensitivity of 75% and a specificity of 67% (AUC = 0.749, 95% CI = 0.692–0.800, p < 0.001). Conclusions: Our study demonstrates that the LAR independently predicts AKI in patients with PE. This is the first study that precisely examines this association in PE patients, as far as we are aware.
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Open AccessArticle
Time-of-Day-Dependent Post-Induction Hypotension and Personalized Hemodynamic Management in Emergency Spine Surgery: A Retrospective Pre–Post Cohort Study
by
Cheol Lee, Eunsung Park, Jina Kim and Kwangjin Lee
Medicina 2026, 62(3), 473; https://doi.org/10.3390/medicina62030473 - 2 Mar 2026
Abstract
Background and Objectives: Post-induction hypotension (PIH) is common in emergency spine surgery and may vary by time of day. We evaluated whether a personalized hemodynamic management (PHM) bundle was associated with reduced PIH and hypotension burden. Materials and Methods: We conducted
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Background and Objectives: Post-induction hypotension (PIH) is common in emergency spine surgery and may vary by time of day. We evaluated whether a personalized hemodynamic management (PHM) bundle was associated with reduced PIH and hypotension burden. Materials and Methods: We conducted a single-center retrospective pre–post cohort study of adults undergoing emergency decompressive or stabilizing spine surgery under general anesthesia. The PHM bundle included documentation of an individualized pre-induction MAP target (default 65 mmHg; higher for selected high-risk phenotypes), dynamic assessment of fluid responsiveness, and proactive vasopressor use (norepinephrine initiated at induction in prespecified high-risk patients), with continuous BP trajectory monitoring. PIH was defined as mean arterial pressure (MAP) < 65 mmHg or a ≥30% decrease from pre-induction MAP within 20 min. We used 1:1 propensity score matching (caliper 0.2) and provider-clustered logistic regression in the matched cohort. Results: Among 312 eligible patients (usual care n = 200; PHM n = 112), PIH varied by time of day, with the highest incidence in morning cases (46.2%; p = 0.041). After matching, 224 patients (112 per group) were analyzed. PHM was associated with lower PIH (43.8% vs. 33.0%; adjusted odds ratio 0.62; 95% CI: 0.41–0.94; p = 0.024). PHM reduced time-weighted average (TWA) MAP below target (5.7 ± 4.2 vs. 3.2 ± 3.6 mmHg; mean difference (MD) −2.3 mmHg; 95% CI −3.3 to −1.3; p = 0.001) and area under MAP < 65 mmHg (ratio 0.62; 95% CI 0.50–0.78; p < 0.001). Norepinephrine-equivalent dose was higher (Δ + 20 μg; p = 0.005) while rescue phenylephrine boluses were fewer (Δ − 1; p < 0.001); crystalloid volume was similar (p = 0.151). Conclusions: In emergency spine surgery, PIH showed time-of-day variation, and PHM implementation was associated with reduced PIH and hypotension burden.
Full article
(This article belongs to the Section Intensive Care/ Anesthesiology)
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Open AccessCorrection
Correction: Bhavsar et al. Female Disparity in Referral to Cardiac Diagnostication and Invasive Treatment. Medicina 2026, 62, 144
by
Rajesh Bhavsar, Leif Thuesen and Carl-Johan Jakobsen
Medicina 2026, 62(3), 472; https://doi.org/10.3390/medicina62030472 - 2 Mar 2026
Abstract
Error in Table [...]
Full article
(This article belongs to the Special Issue Acute Cardiovascular Events: Broadening Perspectives in Acute Care)
Open AccessArticle
Directional Asymmetry of Crossover Neuromuscular Fatigue Following Unilateral Handgrip Exercise in Adults and Prepubertal Children
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Aymen Ben Othman, Wissem Dhahbi, Manel Bessifi, Halil İbrahim Ceylan, Valentina Stefanica, Rihab Moncer and Helmi Ben Saad
Medicina 2026, 62(3), 471; https://doi.org/10.3390/medicina62030471 - 2 Mar 2026
Abstract
Background and Objectives: This study investigated whether crossover neuromuscular fatigue following unilateral handgrip exercise exhibits directional asymmetry, testing whether dominant-limb fatigue produces greater contralateral performance decrements than non-dominant-limb fatigue in adults and pre-peak-height-velocity children. Materials and Methods: Thirty-three healthy, right-handed males
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Background and Objectives: This study investigated whether crossover neuromuscular fatigue following unilateral handgrip exercise exhibits directional asymmetry, testing whether dominant-limb fatigue produces greater contralateral performance decrements than non-dominant-limb fatigue in adults and pre-peak-height-velocity children. Materials and Methods: Thirty-three healthy, right-handed males (16 adults: 22.5 ± 1.6 years; 17 pre-peak-height-velocity boys: 11.2 ± 0.8 years, maturity offset −2.2 ± 0.4 years) completed three counterbalanced experimental sessions (48–72 h apart): dominant-arm fatigue, non-dominant-arm fatigue, and control. The fatigue protocol consisted of 20 consecutive 6 s maximal voluntary isometric handgrip contractions. Primary outcomes were percentage changes in maximal voluntary isometric contraction of the contralateral limb across handgrip, elbow flexor, and elbow extensor muscle groups. Results: The experimental condition explained approximately 64% of crossover variance in adults (ηp2 = 0.650, ηG2 = 0.421) and children (ηp2 = 0.638, ηG2 = 0.448; both p < 0.001). Dominant-limb fatigue elicited substantially greater contralateral decrements than non-dominant-limb fatigue in adults (−11.00% vs. −3.92%, dz = −1.07) and children (−12.71% vs. −3.08%, dz = −1.33), representing 2.5- to 3.5-fold greater transfer efficiency (both p < 0.001). Age-group comparisons revealed no differences in crossover susceptibility (p = 0.627, ηp2 = 0.008), with equivalence testing confirming developmental invariance. Crossover effects extended to heterologous proximal muscles without magnitude differences (p > 0.13). Conclusions: Crossover fatigue (contralateral performance decrement following unilateral exercise) exhibited directional asymmetry, with dominant-limb protocols eliciting 2.5- to 3.5-fold greater contralateral decrements. This pattern aligns with asymmetric transcallosal inhibitory projections demonstrated in prior transcranial magnetic stimulation studies, though direct neurophysiological confirmation was not obtained. Functional equivalence between pre-peak-height-velocity children and adults indicates that interhemispheric transfer mechanisms achieve operational maturity before peak height velocity. Extension to heterologous muscles implicates supraspinal mechanisms. The findings establish normative parameters for clinical populations with compromised transcallosal integrity.
Full article
(This article belongs to the Section Sports Medicine and Sports Traumatology)
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Open AccessArticle
Electronic Stethoscope Auscultation and Echocardiography in ARDS: Correlation and Prognostic Value for Mortality and ICU Length of Stay: A Prospective Observational Study
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Ioannis Alevroudis, Serafeim-Chrysovalantis Kotoulas, Christina Mouratidou, Aliki Karkala, Anastasia Michailidou, Myrto Tzimou, Spyridon Synodinos-Kamilos, Chrysavgi Giannaki, Christos Karachristos, Athina Lavrentieva, Nicos Maglaveras and Evangelos Kaimakamis
Medicina 2026, 62(3), 470; https://doi.org/10.3390/medicina62030470 - 1 Mar 2026
Abstract
Background and Objectives: Acute respiratory distress syndrome (ARDS) carries high mortality, with cardiovascular complications frequently contributing to adverse outcomes. This study investigated the relationship between cardiac auscultation using electronic stethoscopy and echocardiographic findings and evaluated their prognostic significance in mechanically ventilated ARDS
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Background and Objectives: Acute respiratory distress syndrome (ARDS) carries high mortality, with cardiovascular complications frequently contributing to adverse outcomes. This study investigated the relationship between cardiac auscultation using electronic stethoscopy and echocardiographic findings and evaluated their prognostic significance in mechanically ventilated ARDS patients. Materials and Methods: This prospective observational study enrolled 173 consecutive adults with ARDS requiring mechanical ventilation (June 2020–June 2021). Cardiac auscultation was performed using an electronic stethoscope at four standard valvular positions. Bedside echocardiography assessed ventricular function, valvular regurgitation, right ventricular systolic pressure (RVSP), and inferior vena cava dimensions. Primary outcomes were ICU and 90-day mortality; the secondary outcome was ICU length of stay. Results: ICU mortality was 42.2% and 90-day mortality 46.8%. Auscultation findings correlated significantly with echocardiographic parameters: aortic stenosis murmur with an elevated aortic valve velocity (p = 0.009), and mitral/tricuspid regurgitation murmurs with corresponding color Doppler findings (p < 0.001). In multivariate analysis, the mean daily SOFA score (OR 2.39, 95% CI 1.57–3.64, p < 0.001) and RVSP (OR 1.07, 95% CI 1.02–1.11, p = 0.006) independently predicted ICU mortality. For 90-day mortality, the APACHE II score (OR 1.25, p = 0.006), mean daily SOFA score (OR 1.54, p = 0.039), RVSP (OR 1.07, p = 0.020), and mitral regurgitation severity (OR 2.98, p = 0.031) were independent predictors. ICU length of stay was predicted by the mean daily SOFA score (r = 0.35, p < 0.001) and tricuspid regurgitation severity (r = 0.25, p = 0.012). Conclusions: Electronic stethoscope auscultation correlates with the echocardiographic findings in ARDS patients. The RVSP and SOFA scores independently predict mortality, while valvular regurgitation severity provides additional prognostic information for long-term survival and ICU resource utilization.
Full article
(This article belongs to the Special Issue Advances in Echocardiography for Critical Care Management: Challenges and Innovations)
Open AccessArticle
Knee Osteoarthritis (KOA) Severity Influences Proximal Femoral Biomechanics and Predicts Pertrochanteric Fracture Instability: A Retrospective Radiographic Study
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Seyed Ali Hashemi, Bahram Abedini, Hossein Hosseini, Shayan Yousufzai, Christos Koutserimpas, Georgi P. Georgiev, George Tiantafyllou, Eva Diomidous, George Tsakotos, Ioannis Paschopoulos, Fotios Kantas and Maria Piagkou
Medicina 2026, 62(3), 469; https://doi.org/10.3390/medicina62030469 - 1 Mar 2026
Abstract
Background and Objectives: Intertrochanteric hip fractures (ITFs) are common in older adults and frequently coexist with knee osteoarthritis (KOA). Although both conditions share key biomechanical risk factors, the specific relationship between KOA severity and ITF stability has not been well defined. Recent evidence
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Background and Objectives: Intertrochanteric hip fractures (ITFs) are common in older adults and frequently coexist with knee osteoarthritis (KOA). Although both conditions share key biomechanical risk factors, the specific relationship between KOA severity and ITF stability has not been well defined. Recent evidence suggests that degenerative knee changes may alter lower-limb load distribution and increase susceptibility to unstable fracture patterns. This study evaluated whether KOA severity, graded using the Kellgren–Lawrence (KL) system, is associated with ITF stability according to the 2018 AO/OTA classification. Materials and Methods: A retrospective observational study was conducted on 138 patients with IHFs treated between 2018 and 2023. KOA severity was assessed using KL grades I–IV on non-weight-bearing anteroposterior knee radiographs. Lateral wall thickness (LWT) was measured using the Hsu method, with <20.5 mm indicating fracture instability. Statistical analyses included correlation, linear regression, logistic regression, and receiver operating characteristic (ROC) curve analysis to examine the association between KL grade and fracture stability. Results: Among 138 patients, 98 (71.0%) had unstable ITFs. Advanced KOA was significantly more common in the unstable group (KL III 45.9%, KL IV 48.0%; p < 0.001). KL grade showed a significant inverse correlation with LWT (Pearson’s r = −0.394, p < 0.001). Each one-grade increase in KL severity was associated with a 3.8 mm reduction in LWT (p < 0.001). In multivariable logistic regression, KL grade remained an independent predictor of fracture instability (adjusted OR = 4.9, 95% CI: 2.8–8.8, p < 0.001), whereas age and comorbidities were not significant. ROC analysis demonstrated good discriminatory power (AUC = 0.79). A KL ≥ III threshold achieved 95% sensitivity and 56% specificity for predicting instability. Conclusions: Higher KOA severity is strongly associated with unstable ITF patterns. KL grade independently predicts instability and may serve as a simple, accessible radiographic indicator of biomechanical vulnerability and fracture risk in older adults. Incorporating KOA severity into the preoperative evaluation may enhance risk stratification, guide selection of fixation strategy, and support individualized rehabilitation planning.
Full article
(This article belongs to the Special Issue Clinical Research in Orthopaedics and Trauma Surgery)
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Open AccessArticle
Large-Scale Data Analytics of the Romanian National Inpatient Database: Prevalence, Incidence, and Mortality of Chronic Wounds, 2017–2022
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Mona Taroi (Yassin Cataniciu), Liliana Vecerzan (Novac), Ilie Gligorea, Sorin Radu Fleacă, Doru Florian Cornel Moga, Adrian Gheorghe Boicean, Cosmin Ioan Mohor, Adrian Nicolae Cristian, Horațiu Paul Domnariu, Augusta Rațiu, Florin Daniel Sofonea and Carmen Daniela Domnariu
Medicina 2026, 62(3), 468; https://doi.org/10.3390/medicina62030468 - 28 Feb 2026
Abstract
Background and Objectives: Assessing the national burden of chronic wounds is a complex data analytics challenge. Robust estimates in Eastern Europe are scarce, highlighting the need for computational methods to validate cases in large-scale health databases. Materials and Methods: We applied
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Background and Objectives: Assessing the national burden of chronic wounds is a complex data analytics challenge. Robust estimates in Eastern Europe are scarce, highlighting the need for computational methods to validate cases in large-scale health databases. Materials and Methods: We applied a large-scale data analytics approach to Romania’s National Inpatient Database (public hospitals, 2017–2022). A computational case-ascertainment algorithm (validated “≥2 admissions” rule) was used to identify recurrently hospitalized patients, establishing a cohort of 18,856 patients (65,771 hospitalizations). We computed annual prevalence, incidence, and mortality per 100,000 adults, stratified by ulcer categories, age, and sex. Results: Hospital-treated prevalence and incidence showed a clear pre-pandemic peak followed by a marked decline in 2020–2021 and only partial rebound by 2022, consistent with pandemic-related disruption of inpatient care. Population-level mortality remained low, but pressure ulcers, although least frequent, accounted for the highest mortality burden. Venous ulcers were the most common category, and the hospital-treated burden was concentrated in adults aged ≥ 65 years and in men. Conclusions: This nationwide data-analytics framework provides the first validated inpatient indicators of chronic ulcer burden in Romania and demonstrates substantial hospital-treated disease burden with pronounced sensitivity to healthcare access constraints. Clinical Implications: The findings can support health-policy and prevention strategies by prioritizing early detection and integrated hospital–community wound care pathways for high-risk groups (men and older adults) and by strengthening outpatient services to reduce avoidable admissions.
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(This article belongs to the Section Dermatology)
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Prognostic Value of Systemic Inflammation Markers (NLR and Haemoglobin) in Non-Small Cell Lung Cancer: Survival Analysis from a Real-World Single-Centre Cohort Study
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Carina Maria Golban, Lavinia Davidescu, Alexandru Alexandru, Silviu Vlad, Alina Gabriela Negru, Sorin Saftescu, Petrescu Codruta Ileana, Catalin Prodan Barbulescu and Serban Mircea Negru
Medicina 2026, 62(3), 467; https://doi.org/10.3390/medicina62030467 - 28 Feb 2026
Abstract
Background and Objectives: In real-world NSCLC management, prognostic assessment extends beyond tumour staging and molecular profiling, which represent a partial timeframe of disease biology. Routinely collected inflammatory and haematological markers may better reflect the dynamic host–tumour interactions during treatment. This study assessed
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Background and Objectives: In real-world NSCLC management, prognostic assessment extends beyond tumour staging and molecular profiling, which represent a partial timeframe of disease biology. Routinely collected inflammatory and haematological markers may better reflect the dynamic host–tumour interactions during treatment. This study assessed the prognostic significance of baseline and longitudinal neutrophil-to-lymphocyte ratio (NLR) and haemoglobin levels on survival outcomes in a real-world NSCLC cohort. Materials and Methods: We conducted a retrospective observational cohort study of 615 patients with histologically confirmed NSCLC diagnosed between 1 May 2022 and 30 April 2024 at a tertiary referral centre in western Romania. Survival outcomes, including progression-free and overall survival, were analysed through Kaplan–Meier curves, complemented by 12-month restricted mean survival time estimates. High NLR was defined as ≥3 and low haemoglobin as <12 g/dL. Longitudinal changes were evaluated at 6 and 12 months, with 12-month analyses restricted to patients alive at that landmark. Results: The cohort had a median age of 66 years (IQR 60–72) and was predominantly male (66.3%). Most patients presented with advanced disease (60.3% stage IV, 23.6% stage III). At baseline, 57.1% (n = 351) exhibited high NLR and 39.8% (n = 245) had low haemoglobin. Median PFS was 9.0 months (IQR 4.5–15.5), and median OS was 16.5 months (IQR 8.5–27.0). Stage IV disease was associated with shorter PFS than stages I–II (7.0 vs. 20.8 months; log-rank p < 0.001). High-baseline NLR showed a borderline association with shorter PFS (adjusted HR 1.40; 95% CI 0.98–1.95). Among the 436 patients alive at 12 months, NLR increased in 56.7% of cases, and this increase showed a non-significant trend toward shorter PFS (HR 1.35; 95% CI 0.95–1.90; p = 0.09) in a 12-month landmark analysis. Conclusions: Baseline systemic inflammation and anaemia are highly prevalent in real-world NSCLC patients and cluster with advanced disease. Elevated NLR was associated with poorer survival outcomes, whereas low haemoglobin did not demonstrate a significant independent association in adjusted analyses. These haematological parameters are accessible tools for prognostic assessment in routine clinical practice.
Full article
(This article belongs to the Section Oncology)
Open AccessArticle
Detection of Liver Dysfunction in Severe Burn Injury with Bedside Measurement of Perfusion
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Marianne Kruse, András Varga, Berthold Hoppe, Alexander Hoenning, Martin Aman, Klaus Hahnenkamp, Marc Dominik Schmittner and Volker Gebhardt
Medicina 2026, 62(3), 466; https://doi.org/10.3390/medicina62030466 - 28 Feb 2026
Abstract
Background and Objectives: Severe burn injuries are still associated with high mortality. The length of intensive care stay is strongly influenced by the severity of organ failure, with multi-organ failure being the main cause of death in up to 40% of cases. Liver
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Background and Objectives: Severe burn injuries are still associated with high mortality. The length of intensive care stay is strongly influenced by the severity of organ failure, with multi-organ failure being the main cause of death in up to 40% of cases. Liver dysfunction is the second most common organ failure. Conventional diagnosis relies on static laboratory parameters that reflect damage already caused. Measuring the hepatic clearance of indocyanine green (LiMON®) offers a dynamic, bedside method for detecting liver dysfunction early, enabling timely therapy adjustments. Materials and Methods: In this prospective single-centre observational study, all patients admitted to the Unfallkrankenhaus Berlin Burns Centre from October 2022 to September 2024 with ≥30% TBSA burns were included. Liver function was assessed via LiMON® within 24 h post-injury and every 48 h until day 14 or ICU discharge. Static liver parameters were measured in parallel. Results: We included a total of 23 patients. An initial measurement was only successful in 18 cases. On admission, six patients (33%) had normal liver function with a plasma duration rate (PDR) > 18% (PDR 30.9 ± 7.3%), while 12 (67%) showed reduced clearance (PDR 14.5 ± 2.6%). In 75% of cases (n = 9), function recovered within 48 h. Based on PDR progression, four liver function patterns were defined: “stable”, “recovery”, “late insufficiency”, and “failure”; a fifth pattern included all patients who were deceased during this study (“death”). These groups differed in fluid therapy, plasma transfusion, and catecholamines administered. PDR correlated well with aminotransferase levels. Conclusions: Dynamic liver function monitoring enables earlier detection of impairment than static markers. Early identification of at-risk patients could guide fluid management and improve outcomes. LiMON® is a valuable tool in burn care, though alternative methods may be needed in patients with severe systemic hypoperfusion.
Full article
(This article belongs to the Special Issue Burn Injuries: From Intensive Care to Rehabilitation—Multidisciplinary Approaches to Optimizing Survival, Function, and Quality of Life)
Open AccessReview
Pleiotropic Effects of Cardiac Resynchronization Therapy on Cardiometabolic Modulation in Heart Failure
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Panagiotis Theofilis, Panagiotis Iliakis, Aikaterini-Eleftheria Karanikola, Michail Botis, Kyriaki Mavromoustakou, Panagiotis Xydis, Nikolaos Ktenopoulos, Paschalis Karakasis, Ioannis Leontsinis, Christina Chrysohoou and Konstantinos Tsioufis
Medicina 2026, 62(3), 465; https://doi.org/10.3390/medicina62030465 - 28 Feb 2026
Abstract
Cardiac resynchronization therapy (CRT) is a cornerstone intervention for patients with heart failure (HF) and electrical dyssynchrony, improving quality of life, functional capacity, and survival. Beyond mechanical synchrony, mounting evidence suggests CRT exerts systemic and myocardial cardiometabolic benefits. CRT acutely enhances mechanical efficiency
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Cardiac resynchronization therapy (CRT) is a cornerstone intervention for patients with heart failure (HF) and electrical dyssynchrony, improving quality of life, functional capacity, and survival. Beyond mechanical synchrony, mounting evidence suggests CRT exerts systemic and myocardial cardiometabolic benefits. CRT acutely enhances mechanical efficiency and shifts substrate utilization toward greater oxidation of fatty acids and ketones, effects that correlate with long-term reverse remodeling on cardiac magnetic resonance imaging. Earlier metabolomic profiling demonstrated that CRT normalizes circulating energy metabolites, improving Krebs cycle intermediates and substrate balance between glucose and lipids, while baseline metabolite patterns may differentiate responders from non-responders. These metabolic adaptations accompany favorable changes in diastolic performance, right ventricular function, and ventriculo-arterial coupling. In parallel, improved splanchnic perfusion and reduced congestion may ameliorate gut dysbiosis and endotoxemia, mitigating systemic inflammation. Collectively, these findings position CRT as a therapy capable of both mechanical and metabolic restoration in advanced HF. In this review, we discuss the emerging data on how CRT reconditions myocardial energy metabolism, influences ventricular–arterial interactions, and modulates peripheral and gut-derived metabolic pathways.
Full article
(This article belongs to the Special Issue Diabetes, Hypertension, and Cardiovascular Diseases: New Insights, Risk Factors, and Drug Therapies)
Open AccessSystematic Review
Non-Infectious Causes for Elevated Procalcitonin
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Stefan Lucian Popa, Victor Incze, Abdulrahman Ismaiel, Teodora Surdea-Blaga, Simona Grad, Daria Claudia Turtoi, Darius-Stefan Amarie, Liliana David, Vlad Dumitru Brata, Daniel Corneliu Leucuta, Ahmed Abdelghafar, Claudia Diana Gherman, Mihai Razvan Zahan and Dinu Iuliu Dumitrascu
Medicina 2026, 62(3), 464; https://doi.org/10.3390/medicina62030464 - 28 Feb 2026
Abstract
Background and Objectives: Procalcitonin (PCT) is widely used to support the diagnosis of bacterial infection and sepsis, yet clinically relevant elevations also occur in multiple non-infectious conditions. This systematic review aimed to synthesize human evidence on non-infectious causes of elevated PCT and
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Background and Objectives: Procalcitonin (PCT) is widely used to support the diagnosis of bacterial infection and sepsis, yet clinically relevant elevations also occur in multiple non-infectious conditions. This systematic review aimed to synthesize human evidence on non-infectious causes of elevated PCT and to summarize proposed pathophysiological mechanisms, with the goal of supporting context-based interpretation in clinical practice. Materials and Methods: A systematic search of PubMed/MEDLINE, Embase, Web of Science, and Scopus was performed from inception to 31 July 2025. Human studies published in English reporting quantitative PCT values in non-infectious contexts were eligible (observational studies, clinical trials, and case series with ≥5 patients). Results: Seventy-six unique studies were included. Evidence was organized across systemic inflammatory responses, cardiovascular pathology, nephrological disorders and renal replacement therapy, pulmonary diseases, gastrointestinal and hepatopancreatic diseases, autoimmune and rheumatologic conditions, neurologic and ophthalmologic conditions, onco-hematologic disorders, surgery, traumatology and transplanted patients. Across conditions, non-infectious PCT elevations were variable and frequently overlapped with ranges reported in bacterial infection, particularly in settings characterized by severe sterile inflammation and tissue injury (e.g., major surgery, trauma, shock, pancreatitis, and burns), as well as in selected malignancies with tumor-associated PCT production. Conclusions: Elevated PCT is not synonymous with bacterial infection. Interpretation should emphasize clinical context, timing, and serial trends rather than isolated thresholds, especially in high-acuity settings with strong non-infectious inflammatory stimuli. Standardized reporting of assays and sampling time points and condition-specific kinetic data are needed to refine diagnostic and stewardship algorithms.
Full article
(This article belongs to the Special Issue New Insights in the Diagnosis and Treatment of Sepsis and Septic Shock: From Prevention to Multiorgan Failure)
Open AccessReview
From Surgery to Endoscopy: Comprehensive Review of Bariatric Approaches in Pediatric and Adolescent Patients
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Carola D’Agostino, Michela Orsi, Alain Garcia Vázquez, Silvana Perretta and Elisa Reitano
Medicina 2026, 62(3), 463; https://doi.org/10.3390/medicina62030463 - 28 Feb 2026
Abstract
Background and Objectives: Pediatric and adolescent obesity is a growing global health concern that is often associated with cardiometabolic comorbidities. Lifestyle interventions represent first-line therapy; however, many adolescents with moderate-to-severe obesity fail to achieve clinically meaningful weight loss. The objective of this
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Background and Objectives: Pediatric and adolescent obesity is a growing global health concern that is often associated with cardiometabolic comorbidities. Lifestyle interventions represent first-line therapy; however, many adolescents with moderate-to-severe obesity fail to achieve clinically meaningful weight loss. The objective of this review is to provide a comprehensive overview of surgical and endoscopic interventions for adolescent obesity. Materials and Methods: A structured search of PubMed, Scopus, Web of Science and the Cochrane Library was conducted. Studies reporting outcomes of bariatric surgery (sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB)) and endoscopic interventions (endoscopic sleeve gastroplasty (ESG) and intragastric balloons (IGBs)) in patients ≤ 21 years were included. Data on weight loss, BMI reduction, metabolic outcomes, adverse events and follow-up were extracted and summarized. Results: Bariatric surgery remains the most effective intervention, with SG and RYGB achieving substantial and durable weight loss and high rates of comorbidity remission. ESG is an emerging intervention with preliminary short-term efficacy and safety data, though evidence is limited to small pediatric cohorts. IGBs provide reversible, non-surgical weight reduction with consistent short-term efficacy, but long-term durability is variable and largely dependent on adherence to behavioral programs. Across all interventions, psychosocial support, family involvement and multidisciplinary care significantly influence the outcomes. Conclusions: Procedural interventions play a pivotal role in adolescents with moderate-to-severe obesity. IGBs could represent a minimally invasive, reversible option, particularly as bridging or adjunctive therapy. Prospective, long-term studies are needed to optimize patient selection, evaluate developmental safety and determine sustainable outcomes.
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(This article belongs to the Special Issue Bariatric Surgery: New Techniques and Patient Outcomes)
Open AccessReview
Molecular Mechanisms Underlying the Pathogenicity of Pseudomonas aeruginosa
by
Angelika Krūmiņa, Aigars Reinis, Agneta Jeske, Indra Zeltiņa and Ludmila Vīksna
Medicina 2026, 62(3), 462; https://doi.org/10.3390/medicina62030462 - 28 Feb 2026
Abstract
Background and Objectives: Pseudomonas aeruginosa is a versatile, opportunistic pathogen responsible for a wide spectrum of infections, particularly in immunocompromised patients and those with disrupted epithelial barriers and chronic respiratory conditions. Its clinical significance is amplified by intrinsic and acquired antibiotic resistance,
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Background and Objectives: Pseudomonas aeruginosa is a versatile, opportunistic pathogen responsible for a wide spectrum of infections, particularly in immunocompromised patients and those with disrupted epithelial barriers and chronic respiratory conditions. Its clinical significance is amplified by intrinsic and acquired antibiotic resistance, contributing to high mortality rates and treatment challenges. The bacterium’s pathogenic success stems from a multifaceted repertoire of virulence factors, including adhesins, pili, fimbriae, flagella, exopolysaccharides, biofilm-associated proteins, secreted toxins, proteases, lipases, phospholipases, rhamnolipids and redox-active metabolites. These factors are tightly regulated through complex networks, such as quorum sensing and c-di-GMP signaling, enabling dynamic adaptation to host environments and modulation of acute and chronic infection phenotypes. Biofilm formation and nutrient acquisition strategies further support survival in resource-limited conditions and protect against immune clearance and antibiotic pressure. Antibiotic resistance in P. aeruginosa limits therapeutic options. In addition, it may indirectly enhance virulence through modulation of stress responses and quorum sensing. P. aeruginosa’s pathogenicity emerges from the synergy between traditional virulence determinants and adaptive survival strategies, supporting long-term persistence, chronic infection, and resistance to host immunity and therapy. Materials and Methods: This narrative review is based on a comprehensive analysis of recent peer-reviewed literature focusing on virulence regulation, biofilm formation, nutrient acquisition strategies, and the interplay between antibiotic resistance and pathogenicity. Results: The reviewed evidence indicates that virulence expression in P. aeruginosa is highly dynamic and context-dependent, with regulatory networks integrating environmental signals to fine-tune pathogenic responses. A consistent finding across studies is the central role of biofilm-associated adaption in promoting persistence and antimicrobial tolerance. Moreover, the interaction between resistance mechanisms and global regulatory pathways appears to enhance bacterial fitness and long-term survival within the host. Conclusions: A deeper understanding of these interconnected mechanisms may facilitate the development of more effective anti-virulence and therapeutic strategies.
Full article
(This article belongs to the Section Infectious Disease)
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Open AccessSystematic Review
Clinical Utility of Circulating Tumour DNA (ctDNA) Analysis for Assessing Completeness of Primary Lesion Resection and Disease Stage in Patients with Melanoma: A Systematic Review
by
Monika Wojarska, Klaudia Kokot, Paulina Bernecka, Aleksandra Kierczak, Natalia Sitkiewicz, Aleksandra Wakszyńska, Tomasz Wichowski, Weronika Skok, Milena Matwiejczuk, Wiktor Lijewski and Jerzy Jankau
Medicina 2026, 62(3), 461; https://doi.org/10.3390/medicina62030461 - 28 Feb 2026
Abstract
Background and Objectives: Melanoma is an aggressive cutaneous malignancy with a high recurrence rate even after complete resection. Circulating tumour DNA (ctDNA) has emerged as a promising biomarker for detecting minimal residual disease (MRD), assessing tumour burden, and predicting recurrence. This study aims
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Background and Objectives: Melanoma is an aggressive cutaneous malignancy with a high recurrence rate even after complete resection. Circulating tumour DNA (ctDNA) has emerged as a promising biomarker for detecting minimal residual disease (MRD), assessing tumour burden, and predicting recurrence. This study aims to evaluate the clinical utility of ctDNA analysis in determining completeness of melanoma resection and disease staging. Materials and Methods: A systematic review was conducted in accordance with PRISMA guidelines, searching PubMed and Web of Science for studies published between January 2017 and February 2025. Eligible studies assessed ctDNA before, during, or after melanoma resection to evaluate surgical completeness and staging. Studies without perioperative ctDNA assessment or which focused solely on immunotherapy efficacy were excluded. Results: Fourteen studies with 1077 patients met the inclusion criteria. Preoperative ctDNA detection correlated with advanced stage, greater tumour burden, and poorer survival. Postoperative ctDNA persistence was strongly associated with recurrence, often detectable months before clinical relapse. In most patients remaining disease-free, ctDNA cleared within weeks after surgery. ctDNA levels reflected metastatic spread, though sensitivity was lower for brain lesions. Across studies, undetectable postoperative ctDNA was consistently linked to longer recurrence-free survival. Conclusions: Perioperative ctDNA analysis shows promise as a prognostic biomarker for detecting residual disease and anticipating relapse in melanoma. However, heterogeneity in patient cohorts, study design, and ctDNA detection methods limits immediate clinical application. Large, standardized prospective trials are needed to validate ctDNA for perioperative management.
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(This article belongs to the Section Dermatology)
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Open AccessArticle
Roxadustat for Erythropoiesis-Stimulating Agent Hyporesponsive Anemia in Hemodialysis: Multicenter Retrospective Analysis
by
Ilyas Ozturk, Meliha Ozkutlu, Merve Aktar, Cihan Heybeli, Can Huzmeli, Orhan Ozdemir, Seda Safak Ozturk, Tulin Akagun, Ekrem Kara, Neriman Sila Koc, Mehmet Tuncay and Tuncay Sahutoglu
Medicina 2026, 62(3), 460; https://doi.org/10.3390/medicina62030460 - 28 Feb 2026
Abstract
Background and Objectives: Anemia management in maintenance hemodialysis patients with erythropoiesis-stimulating agent (ESA) hyporesponsiveness remains challenging. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, offers a mechanistically distinct alternative. Materials and Methods: This multicenter retrospective study analyzed 110 hemodialysis patients with persistent anemia (Hemoglobin
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Background and Objectives: Anemia management in maintenance hemodialysis patients with erythropoiesis-stimulating agent (ESA) hyporesponsiveness remains challenging. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, offers a mechanistically distinct alternative. Materials and Methods: This multicenter retrospective study analyzed 110 hemodialysis patients with persistent anemia (Hemoglobin (Hb) < 10 g/dL) despite ≥ 3 months of maximum-reimbursable-dose ESA therapy in Türkiye. Outcomes were evaluated between patients who switched to Roxadustat (n = 80) and those who continued ESA therapy (n = 30) over 6 months in a non-randomized, observational comparison. Results: At baseline, median Hb levels were significantly lower in the Roxadustat-group than in the ESA-group (8.70 vs. 9.50 g/dL; p < 0.001), while weight-adjusted ESA doses were comparable (p = 0.332). By Month 6, the Roxadustat group achieved a significant Hb increase (from 8.70 to 9.95 g/dL), whereas the ESA-group showed no significant change (9.50 to 9.65 g/dL), and end-of-treatment Hb did not differ significantly between groups. The unadjusted mean Hb rise was greater in the Roxadustat cohort than in the ESA cohort (+1.40 ± 1.55 vs. +0.65 ± 1.93 g/dL; p = 0.037). However, after adjustment for baseline Hb (ANCOVA), baseline Hb predicted final Hb, while treatment group was not independently associated with final Hb. Transfusion requirements declined over follow-up in both groups. No new short-term safety signal was identified based on available clinical documentation. Conclusions: Roxadustat improved Hb in ESA-hyporesponsive patients with lower baseline Hb, but adjusted analyses indicated that baseline severity influenced response. Targets were not consistently achieved; these findings are hypothesis-generating regarding dose optimization, treatment duration, and earlier initiation.
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(This article belongs to the Section Urology & Nephrology)
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Open AccessArticle
Key Outcomes for Evaluating Hand and Wrist Scars: A Nationwide Survey of Clinicians in Saudi Arabia
by
Hadeel R. Bakhsh, Raghad W. Alotaibi, Monira I. Aldhahi and Donna L. Kennedy
Medicina 2026, 62(3), 459; https://doi.org/10.3390/medicina62030459 - 28 Feb 2026
Abstract
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Background and Objectives: Hand and wrist scars alter physical appearance and can result in functional impairments and psychosocial difficulties. Although these effects are clinically important, rehabilitation services in Saudi Arabia lack consistent and standardised scar assessment protocols. The limited use of validated outcome
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Background and Objectives: Hand and wrist scars alter physical appearance and can result in functional impairments and psychosocial difficulties. Although these effects are clinically important, rehabilitation services in Saudi Arabia lack consistent and standardised scar assessment protocols. The limited use of validated outcome measures hinders both clinical practice and research. Standardised scar assessment is essential for evidence synthesis, developing new scar care interventions and promoting best outcomes. We aim to investigate healthcare professionals’ perspectives on key scar outcome domains for evaluating hand and wrist scars and identify gaps in current practice and training needs to support the development of evidence-based guidelines. The study design is a cross-sectional descriptive study. Materials and Methods: The Saudi Commission for Health Specialties distributed a survey to 5000 randomly selected licensed healthcare professionals. The adapted questionnaire obtained sociodemographic data, professional experience, and ratings of scar outcome domains using a five-point Likert scale. Descriptive statistics were used for the analyses. Results: The analysis included 74 completed responses (response rate, 41.5%). Nurses (32.4%) and occupational therapists (29.7%) represented the largest groups. Only 37.8% of the participants reported receiving specialised training in scar assessment. Furthermore, the use of outcome measures remained limited, with 41.3% utilising clinician-reported outcome measures (CROMs) and 54.05% using patient-reported outcome measures (PROMs). The Vancouver Scar Scale and Patient and Observer Scar Assessment Scale were the most frequently used assessment tools. Clinicians primarily evaluated physical symptoms, including hypersensitivity (69.8%) and pain (67.6%), as well as scar characteristics such as colour (62.2%), adhesion (65.8%), and thickness (64.9%). Psychological factors were also considered important, particularly self-confidence (59.5%), acceptance of the scar (60.3%), and satisfaction with the scar (60.8%). Conclusions: Healthcare professionals in Saudi Arabia recognise the complex effects of hand and wrist scarring; however, they show limited integration of validated assessment tools, especially patient-reported outcome measures, in clinical practice. This gap suggests the need for targeted training, interdisciplinary educational initiatives, and efforts to strengthen standardised approaches to scar assessment. Exploring the development of future national guidance and engaging in international efforts to develop a core outcome measurement set may support evidence-based evaluation and improved long-term patient outcomes.
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Open AccessReview
Nutritional Status in Obesity: A Comprehensive Narrative Review of Dysbiosis, Micronutrient Deficiencies and the Effects of Probiotics/Synbiotics
by
Andra-Diana Cecan, Adriana-Florinela Cătoi, Anca But and Iulia-Ioana Morar
Medicina 2026, 62(3), 458; https://doi.org/10.3390/medicina62030458 - 28 Feb 2026
Abstract
Obesity is a chronic, relapse-prone disease often associated with comorbidities such as type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease. Intestinal dysbiosis, defined as an imbalance in the composition and function of the gut microbiota, is commonly observed in individuals with excess
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Obesity is a chronic, relapse-prone disease often associated with comorbidities such as type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease. Intestinal dysbiosis, defined as an imbalance in the composition and function of the gut microbiota, is commonly observed in individuals with excess body weight and plays a key role in the development of related metabolic complications. Moreover, dysbiosis can disrupt nutrient metabolism, leading to imbalances in energy homeostasis. Those affected by excess weight frequently exhibit deficiencies in essential vitamins and minerals, which further exacerbate metabolic and inflammatory dysfunctions, accelerating the progression of comorbidities. Studies have shown that the gut microbiota in individuals with obesity differs significantly from that of healthy, normal-weight individuals. Obesity often shows alterations in the relative abundance of Firmicutes and Bacteroidetes (F/B), with individual variability and reduced bacterial diversity, although the F/B ratio alone may not consistently reflect dysbiosis. Prolonged or repeated antibiotic use can further disturb the microbiota, worsening dysbiosis and contributing to the development of excess body weight by impairing energy metabolism and promoting systemic inflammation. Recent evidence suggests that probiotics are a safe and promising therapeutic approach for managing metabolic disorders. Several in vivo and clinical studies have reported a potential causal relationship between probiotic supplementation and the improvement of weight-related conditions. This narrative review aims to explore the alterations of gut microbiota in obesity and their impact on nutritional deficiencies. Additionally, it highlights the potential role of probiotics in restoring microbiota balance and improving metabolic dysfunctions related to excess body weight.
Full article
(This article belongs to the Special Issue Nutritional Management of Adults with Obesity)
Open AccessArticle
Factors Influencing the Course of Hospitalization in Children with Respiratory Syncytial Virus Infection: A Retrospective Single-Center Study at the Department of Pediatrics, Wadowice Hospital, Poland
by
Klaudia Kasperek, Dominik Gałuszka, Agnieszka Sumara and Anna Kurkiewicz-Piotrowska
Medicina 2026, 62(3), 455; https://doi.org/10.3390/medicina62030455 - 28 Feb 2026
Abstract
Background and Objectives: Respiratory syncytial virus (RSV) is a leading cause of hospitalization among infants and young children. The clinical course of RSV infection varies considerably depending on age and selected clinical factors. The objective of this study was to identify demographic
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Background and Objectives: Respiratory syncytial virus (RSV) is a leading cause of hospitalization among infants and young children. The clinical course of RSV infection varies considerably depending on age and selected clinical factors. The objective of this study was to identify demographic and clinical variables associated with the course of hospitalization in children admitted due to laboratory-confirmed RSV infection. Materials and Methods: A retrospective observational study was conducted based on the medical records of 100 immunocompetent pediatric patients hospitalized due to RSV infection in the Department of Pediatrics of Hospital in Wadowice, Poland, between December 2021 and April 2023. Inclusion criteria were age ≤ 5 years and laboratory-confirmed RSV infection. Patients with congenital heart disease, chronic lung disease (including cystic fibrosis), immunodeficiency, or other severe chronic conditions were excluded. Collected data included age, gestational age at birth, mode of delivery, vaccination status, clinical presentation, length of hospital stay, C-reactive protein (CRP) levels, seasonality of infection, and use of antibiotic therapy. Results: The median length of hospitalization was 6 days (range: 0–18). Younger age was significantly associated with longer hospital stay (p < 0.05) and higher CRP levels (p < 0.05). No significant associations were observed between hospitalization duration and mode of delivery or vaccination status. Gestational age at birth did not influence the number of clinical symptoms. The need for antibiotic therapy differed significantly according to the season of infection (p < 0.05). Conclusions: In children hospitalized with RSV infection, age and seasonality were the primary factors influencing the course of hospitalization, whereas perinatal factors such as mode of delivery and vaccination status had no significant impact. These findings underscore the importance of age-oriented clinical assessment and support efforts to optimize antimicrobial stewardship during RSV seasons.
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(This article belongs to the Section Pediatrics)
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Open AccessArticle
Chronic ACL Injury Drives a Fibrotic and Matrix-Degradative Shift: A Multi-Level Analysis of MMP-13 and TGF-β1
by
Yılmaz Mertsoy, Mustafa Altıntaş, Sözdar Güzel and Alpay Çetin
Medicina 2026, 62(3), 457; https://doi.org/10.3390/medicina62030457 - 27 Feb 2026
Abstract
Background and Objectives: The biological state of anterior cruciate ligament (ACL) remnant tissue may influence postoperative healing, yet the molecular changes associated with injury chronicity remain poorly defined. This study evaluated MMP-13 and TGF-β1 expression in human ACL remnants to characterize their
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Background and Objectives: The biological state of anterior cruciate ligament (ACL) remnant tissue may influence postoperative healing, yet the molecular changes associated with injury chronicity remain poorly defined. This study evaluated MMP-13 and TGF-β1 expression in human ACL remnants to characterize their regenerative or fibrotic potential. Materials and Methods: ACL remnants from acute (<3 months) and chronic (>6 months) injuries were analyzed using histology, immunohistochemistry, and QuPath-based digital quantification. Clinical outcomes were correlated with marker expression. Protein–protein interaction and KEGG enrichment analyses were performed to identify extracellular matrix (ECM)-related pathways associated with MMP-13 and TGF-β1. Results: Chronic ACL remnants exhibited disorganized ECM structure with significantly higher MMP-13 and TGF-β1 expression across all digital metrics, including DAB-positive area, cell density, optical density, and H-score (p < 0.01). Higher expression of both markers correlated with lower IKDC and Lysholm scores and greater residual pivot-shift positivity. Bioinformatic analysis identified 39 shared proteins enriched in ECM-receptor interaction, TGF-β signaling, and fibrosis-related pathways, aligning with the degenerative phenotype observed in chronic tissue. Conclusions: ACL remnant biology evolves from a reparative profile in acute injuries to a fibrotic, matrix-degradative state in chronic injuries. MMP-13 and TGF-β1 serve as indicators of remnant quality and may help guide timing of surgery and future biologic strategies aimed at improving ACL reconstruction outcomes.
Full article
(This article belongs to the Special Issue Anterior Cruciate Ligament (ACL) Injury)
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