Journal of Clinical Medicine

25 pages, 1854 KiB

Open AccessEditor’s ChoiceArticle

How Action Shapes Temporal Judgments: A Study in Brain Damaged Patients Through Immersive Virtual Reality

by Greta Vianello, Michela Candini, Giuliana Vezzadini, Valentina Varalta, Gennaro Ruggiero, Tina Iachini and Francesca Frassinetti

J. Clin. Med. 2025, 14(14), 4825; https://doi.org/10.3390/jcm14144825 - 8 Jul 2025

Viewed by 325

Abstract

Background/Objectives: Time processing is crucial for managing several aspects of our daily experiences: the continuous interaction with a changing environment requires individuals to make precise temporal judgments. Following right hemisphere damage, patients exhibited a significant alteration in perceiving temporal duration. However, this [...] Read more.

Background/Objectives: Time processing is crucial for managing several aspects of our daily experiences: the continuous interaction with a changing environment requires individuals to make precise temporal judgments. Following right hemisphere damage, patients exhibited a significant alteration in perceiving temporal duration. However, this impairment usually emerges with “abstract” computerized tasks, not in everyday contexts. This study investigates estimation and reproduction of time intervals in left (LBD) and right brain damaged (RBD) patients compared to healthy controls. Methods: We adopt computerized tasks (Experiment 1) and novel virtual reality (VR) tasks where participants judged the duration of their own actions framed within a realistic VR context (Experiment 2). Results: RBD but not LBD patients underestimated time intervals, and reproduced time intervals as longer than they are. Crucially, when participants judged the temporal duration of meaningful actions performed in a realistic context through the VR scenarios, the impairment in processing time observed in RBD patients was reduced. The Voxel-lesion-symptom-mapping (VLSM) analysis revealed the neurocognitive basis of time perception. Conclusions: Our results show that meaningful actions within familiar contexts can provide a channel of information that is essential for optimal time processing, suggesting the importance of assessing time processing in an ecologically controlled manner using VR. Full article

(This article belongs to the Section Brain Injury)

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13 pages, 1325 KiB

Open AccessEditor’s ChoiceReview

Endoscopic Ultrasound as a Diagnostic Tool for the Mediastinum and Thorax

by Sara Nikolic, Lucía Guilabert, Giuseppe Vanella, Catalina Vladut, Giuseppe La Mattina, Giuseppe Infantino, Elio D’Amore, Cecilie Siggaard Knoph and Giacomo Emanuele Maria Rizzo

J. Clin. Med. 2025, 14(14), 4836; https://doi.org/10.3390/jcm14144836 - 8 Jul 2025

Viewed by 471

Abstract

Endoscopic ultrasound (EUS) is a helpful tool for the study of the mediastinum, a challenging region for both transesophageal and endobronchial (EBUS) endosonography. This area is divided into sections and contains numerous lymph nodes essential for the staging and diagnosis of conditions like [...] Read more.

Endoscopic ultrasound (EUS) is a helpful tool for the study of the mediastinum, a challenging region for both transesophageal and endobronchial (EBUS) endosonography. This area is divided into sections and contains numerous lymph nodes essential for the staging and diagnosis of conditions like lung cancer, sarcoidosis, and infections. EUS allows for detailed examination of the mediastinal region, identifying various kinds of abnormalities, whether they are benign cysts or malignant tumors. The aim of this narrative review is to provide a clear overview of how EUS contributes to mediastinal diagnostics and to offer practical insights for clinicians. A comprehensive, non-systematic search of PubMed was conducted by the authors to identify relevant studies. EUS methods, such as elastography and contrast-enhanced imaging, have improved diagnosis by analyzing tissue stiffness and blood flow, and they help endosonographers distinguish between different conditions. EUS-guided tissue sampling techniques, like fine needle aspiration and biopsy, are crucial for detecting cancer and examining lymph nodes in a minimally invasive way. By combining EUS with endobronchial ultrasound, operators can achieve more accurate results, especially in cancer staging and treatment planning. Overall, this approach is a key tool in treating thoracic and mediastinal conditions. Full article

(This article belongs to the Section Respiratory Medicine)

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17 pages, 1554 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Adverse Events Associated with the Sulfamethoxazole/Trimethoprim Combination Drug

by Takaya Sagawa, Tomoaki Ishida, Kohei Jobu, Shumpei Morisawa, Keita Akagaki, Takahiro Kato, Takumi Maruyama, Yusuke Yagi, Tomomi Kihara, Sanae Suzuki, Mio Endo, Nobuaki Matsunaga and Yukihiro Hamada

J. Clin. Med. 2025, 14(14), 4819; https://doi.org/10.3390/jcm14144819 - 8 Jul 2025

Cited by 1 | Viewed by 682

Abstract

Background/Objectives: The combination drug sulfamethoxazole/trimethoprim (ST) is a broad-spectrum antibiotic used against various infections; however, it is associated with several serious adverse events. The ST package inserts contain warnings about these adverse events. However, warnings vary internationally, and specific measures to address [...] Read more.

Background/Objectives: The combination drug sulfamethoxazole/trimethoprim (ST) is a broad-spectrum antibiotic used against various infections; however, it is associated with several serious adverse events. The ST package inserts contain warnings about these adverse events. However, warnings vary internationally, and specific measures to address ST-related adverse events are unclear. Therefore, we aimed to comprehensively evaluate ST-related adverse events using the Japanese Adverse Drug Event Report (JADER) database and analyze the onset time for each event. Methods: Adverse events due to ST were analyzed using the JADER database between April 2004 and June 2023. The reported odds ratio and 95% confidence interval (95% confidence interval [CI]) were calculated, with a signal detected if the 95% CI lower limit exceeded 1. The Weibull distribution was used to characterize the onset time of adverse events with detected signals. Results: The total number of cases in the JADER database during the study period was 862,952, and the number of adverse events involving ST as a suspected drug was 4203. Adverse events associated with ST include hyperkalemia, syndrome of inappropriate antidiuretic hormone secretion, hematopoietic cytopenia, acute renal failure, hypoglycemia, disseminated intravascular coagulation syndrome, hepatic disorder, and the Stevens–Johnson syndrome/toxic epidermal necrolysis. Conclusions: Weibull analysis indicated an early failure-type onset time for all adverse events, suggesting the need for intensive adverse event monitoring of ST, especially in the first month of use. These findings may support revising drug package inserts in Japan to better reflect the identified risks. Full article

(This article belongs to the Special Issue Targeted Diagnosis and Advances in the Clinical Application of Infectious Diseases)

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12 pages, 353 KiB

Open AccessEditor’s ChoiceArticle

Characteristics and Clinical Implications of Cytomegalovirus Infection in Patients with Drug-Resistant Ulcerative Colitis Undergoing Colectomy—Data from a Tertiary Referral Center in Poland

by Estera Banasik, Paweł Kosikowski, Izabela Miechowicz, Piotr Zelga, Tomasz Banasiewicz, Agnieszka Dobrowolska and Piotr Eder

J. Clin. Med. 2025, 14(14), 4823; https://doi.org/10.3390/jcm14144823 - 8 Jul 2025

Viewed by 343

Abstract

Background/Objectives: This study aimed to assess the frequency, risk factors, and clinical implications of cytomegalovirus (CMV) colitis in patients undergoing colectomy due to refractory ulcerative colitis (UC). Methods: A retrospective analysis was conducted on patients with drug-resistant UC who underwent colectomy [...] Read more.

Background/Objectives: This study aimed to assess the frequency, risk factors, and clinical implications of cytomegalovirus (CMV) colitis in patients undergoing colectomy due to refractory ulcerative colitis (UC). Methods: A retrospective analysis was conducted on patients with drug-resistant UC who underwent colectomy at a tertiary referral center between 2009 and 2017. Histological inflammatory activity in surgical specimens was assessed using the Simplified Geboes Score. The presence and density of CMV expression were estimated immunohistochemically. Preoperative clinical, biochemical, and endoscopic data, as well as the short- and long-term postoperative disease courses, were evaluated in relation to the presence of CMV colitis at the time of surgery. Results: CMV colitis was identified in 14% (7/49) of patients. The CMV-positive group exhibited significantly shorter disease durations and higher C-reactive protein concentrations at the time of surgery. This subgroup also demonstrated consistently numerically higher steroid use, both in terms of the usage frequency and cumulative treatment duration. Patients with concomitant CMV colitis had lower likelihoods of stoma closure and restoration of gastrointestinal continuity in the long-term. Conclusions: Concomitant CMV colitis is not uncommon in patients with treatment-refractory UC. Testing for CMV should be considered, particularly in individuals with a short-term, dynamic, and aggressive disease course unresponsive to standard therapy, especially steroids. Full article

(This article belongs to the Special Issue Inflammatory Bowel Diseases: Clinical Advances and Emerging Therapies)

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12 pages, 985 KiB

Open AccessEditor’s ChoiceArticle

Immediate and Short-Term Intraocular Pressure Changes Following Intravitreal Injection and Associated Factors

by Manabu Yamamoto, Kumiko Hirayama, Akika Kyo, Gen Kinari, Yuki Kojima, Takeya Kohno and Shigeru Honda

J. Clin. Med. 2025, 14(14), 4821; https://doi.org/10.3390/jcm14144821 - 8 Jul 2025

Viewed by 445

Abstract

Objectives: To evaluate the immediate and short-term changes in intraocular pressure (IOP) following intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) agents and to identify the clinical and procedural factors associated with IOP elevation after treatment. Methods: This retrospective study [...] Read more.

Objectives: To evaluate the immediate and short-term changes in intraocular pressure (IOP) following intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) agents and to identify the clinical and procedural factors associated with IOP elevation after treatment. Methods: This retrospective study included 118 eyes from 115 patients who underwent IVI with anti-VEGF agents at Osaka Metropolitan University Hospital between September 2024 and January 2025. IOP was measured at three time points, namely before injection, within 1 min after injection, and at 30 min, in selected eyes with a post-injection IOP ≥ 25 mmHg. Differences in IOP elevation were analyzed according to the disease type and anti-VEGF agent. Univariate and multivariate linear regression analyses were performed to identify clinical factors associated with IOP elevation. Results: Mean IOP significantly increased from 13.9 ± 3.3 mmHg at baseline to 39.2 ± 12.4 mmHg immediately after injection (p < 0.001), with 79.7% of eyes showing an IOP ≥ 25 mmHg. Among those remeasured, IOP decreased to 17.7 ± 6.5 mmHg at 30 min. Significant differences in IOP elevation were observed among anti-VEGF agents (p < 0.001), with aflibercept at 2 mg and 8 mg showing greater increases than other agents. Multivariate analysis identified higher baseline IOP, history of glaucoma, absence of prior vitrectomy, and use of aflibercept (2 mg or 8 mg) as significant risk factors for greater post-injection IOP elevation. Conclusions: Transient IOP elevation ≥ 25 mmHg was observed in the majority of eyes after IVI but typically resolved within 30 min. Aflibercept use, high baseline IOP, glaucoma history, and absence of prior vitrectomy were associated with greater IOP elevation. Careful monitoring and attention to injection volume may be warranted, particularly in high-risk patients. Full article

(This article belongs to the Special Issue An Update on Retinal Diseases: From Diagnosis to Treatment)

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16 pages, 277 KiB

Open AccessEditor’s ChoiceReview

Patient-Reported Outcome Measures in Clinical Practice for Tooth Wear: A Literature Review

by Inês Argolinha, Sofia Lobo, Ana Vieira, João Botelho, João Rua, José J. Mendes and Vanessa Machado

J. Clin. Med. 2025, 14(14), 4816; https://doi.org/10.3390/jcm14144816 - 8 Jul 2025

Viewed by 882

Abstract

Tooth wear is a growing oral health concern with implications for function, esthetics, and psychological well-being, ultimately affecting oral health-related quality of life (OHRQoL). While clinical indices assess tooth wear severity, they fail to capture patient-reported outcomes (PROs) and patient-reported outcome measures (PROMs). [...] Read more.

Tooth wear is a growing oral health concern with implications for function, esthetics, and psychological well-being, ultimately affecting oral health-related quality of life (OHRQoL). While clinical indices assess tooth wear severity, they fail to capture patient-reported outcomes (PROs) and patient-reported outcome measures (PROMs). This narrative review aims to identify and synthesize the use of PROs and PROMs used in adults with tooth wear and to map their assessed domains against the Wilson and Cleary model of health outcomes, highlighting gaps and guiding the development of condition-specific instruments. A comprehensive search of the literature was conducted across PubMed, MEDLINE, and Embase. Studies involving PROMs in adults with tooth wear were included. Extracted data encompassed psychometric properties and domains assessed. PROMs such as the OHIP, OES, OIDP, and QMFQ have been frequently used, focusing on functional limitation, esthetic perception, and psychological distress. However, no single instrument comprehensively addresses all relevant domains of the Wilson and Cleary model. Moreover, variation in tools and constructs limits comparability across studies and clinical settings. Existing PROMs capture only partial aspects of the patient experience related to tooth wear. When mapping these instruments to a validated theoretical model, significant gaps become evident, especially in terms of general health perceptions and overall quality of life metrics. To improve the evaluation and management of tooth wear in clinical settings, it is essential to create a condition-specific PROM based on a solid conceptual framework. Full article

(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)

19 pages, 2467 KiB

Open AccessEditor’s ChoiceSystematic Review

Reconstruction of the Extensor Apparatus After Total Patellectomy in Orthopedic Oncology: A Systematic Literature Review

by Edoardo Ipponi, Fabrizia Gentili, Fabio Cosseddu, Antonio D’Arienzo, Paolo Domenico Parchi and Lorenzo Andreani

J. Clin. Med. 2025, 14(14), 4818; https://doi.org/10.3390/jcm14144818 - 8 Jul 2025

Viewed by 380

Abstract

Background: Patellar resection is recommended in cases of massive cortical bone disruption or malignancies. Modern literature lacks a consensus surgical reconstruction after total patellectomy. Our study reviews the surgical techniques described in the literature and summarizes the reported functional outcomes and complication [...] Read more.

Background: Patellar resection is recommended in cases of massive cortical bone disruption or malignancies. Modern literature lacks a consensus surgical reconstruction after total patellectomy. Our study reviews the surgical techniques described in the literature and summarizes the reported functional outcomes and complication rates. Materials: We systematically reviewed the existing literature, searching the PubMed, Embase, and Scopus databases for articles published between 1950 and 2024. We recorded age, diagnosis, tumor size, Lodwick classification, soft tissue involvement, and pre-operative fractures for each case or case series. We also recorded the reconstructive approaches. Complications, local recurrences, MSTS scores, and knee range of motion (ROM) were considered when reported. Results: Twenty-eight articles met our inclusion criteria. Among these, 4 were case series and 24 were case reports. A total of 47 cases treated with total patellectomy were reviewed. Reconstruction was performed with direct suture in 8 cases, while 17 had local augments, including allograft (10 cases), muscle flaps or transportations (4), autologous bone (1), or a composite (2). Reconstruction was not mentioned in 22 cases. ROM was reported for 17 cases, and the MSTS score was reported for 9 cases. Conclusions: In cases of relatively small tissue defects, a direct suture of the extensor apparatus can allow adequate functional recovery. In cases of larger gaps, surgeons should use muscle flaps, transfers, or soft tissue augments. Massive bone and tendon allografts should mainly be considered in cases where the neoplasm was not confined to the patella but extensively involved the patellar ligament or the quadriceps tendon. Full article

(This article belongs to the Special Issue Diagnosis and Treatment for Bone Tumor)

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10 pages, 431 KiB

Open AccessEditor’s ChoiceArticle

The Kinetics of Microcirculatory Dysfunction During Paclitaxel Application in an In Vivo Mouse Model

by Susanne Reuter, Rika Bajorat, Fabian Müller-Graf, Amelie R. Zitzmann, Stephan H. Böhm, Daniel A. Reuter and Brigitte Vollmar

J. Clin. Med. 2025, 14(14), 4815; https://doi.org/10.3390/jcm14144815 - 8 Jul 2025

Viewed by 331

Abstract

Objective: Chemotherapy-induced peripheral neuropathy often has a lasting impact on the quality of life without existing causal treatment options. The aim of this study was to systematically investigate the temporal occurrence of paclitaxel-induced peripheral microcirculatory dysfunction. Methods: Thirty-one female SKH-1 mice [...] Read more.

Objective: Chemotherapy-induced peripheral neuropathy often has a lasting impact on the quality of life without existing causal treatment options. The aim of this study was to systematically investigate the temporal occurrence of paclitaxel-induced peripheral microcirculatory dysfunction. Methods: Thirty-one female SKH-1 mice received six cycles of paclitaxel intraperitoneally in the treatment group and six cycles of saline in the control group. Intravital fluorescence analyses were performed in the groups 180 min after saline administration and immediately, 60 min, 120 min, and 180 min after paclitaxel administration to evaluate the effects on microcirculation and inflammation. Results: In addition to signs of systemic inflammation, the intravital microscopy revealed a marked reduction in functional capillary density, increased venous leukocyte adhesion, and endothelial permeability that persisted for at least three hours in paclitaxel-treated mice. Conclusions: Our results show that paclitaxel-induced microcirculatory disturbances manifest immediately after application and last at least for 3 h. This suggests that options for prevention or at least amelioration could potentially be most effective if initiated parallel to the induction of chemotherapy and continued for a prolonged period of at least 3 h. Whether and to what extent the prolongation of the preventive strategies influences CIPN in the long term needs to be studied further. Full article

(This article belongs to the Section Pharmacology)

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17 pages, 923 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

From Clicks to Care: Enhancing Clinical Decision Making Through Structured Electronic Health Records Navigation Training

by Savita Ramkumar, Isaa Khan, See Chai Carol Chan, Waseem Jerjes and Azeem Majeed

J. Clin. Med. 2025, 14(14), 4813; https://doi.org/10.3390/jcm14144813 - 8 Jul 2025

Viewed by 612

Abstract

Background: The effective use of electronic health records (EHRs) is an essential clinical skill, but medical schools have traditionally provided limited systematic teaching on the topic. Inefficient use of EHRs results in delays in diagnosis, fragmented care, and clinician burnout. This study [...] Read more.

Background: The effective use of electronic health records (EHRs) is an essential clinical skill, but medical schools have traditionally provided limited systematic teaching on the topic. Inefficient use of EHRs results in delays in diagnosis, fragmented care, and clinician burnout. This study investigates the impact on medical students’ confidence, efficiency, and proficiency in extracting clinically pertinent information from patient records following an organised EHR teaching programme. Methods: This observational cohort involved 60 final-year medical students from three London medical schools. Participants received a structured three-phase intervention involving an introductory workshop, case-based hands-on practice, and guided reflection on EHR navigation habits. Pre- and post-intervention testing involved mixed-method surveys, simulated case tasks, and faculty-assessed data retrieval exercises to measure changes in students’ confidence, efficiency, and ability to synthesise patient information. Quantitative data were analysed using paired t-tests, while qualitative reflections were theme-analysed to identify shifts in clinical reasoning. Results: All 60 students successfully finished the intervention and assessments. Pre-intervention, only 28% students reported feeling confident in using EHRs effectively, with a confidence rating of 3.0. Post-intervention, 87% reported confidence with a rating of 4.5 (p < 0.01). Efficiency in the recovery of critical patient information improved from 3.2 to 4.6 (p < 0.01). Students also demonstrated enhanced awareness regarding system-related issues, such as information overload and fragmented documentation, and provided recommendations on enhancing data synthesis for clinical decision making. Conclusions: This study emphasises the value of structured EHR instruction in enhancing the confidence and proficiency of medical students in using electronic records. The integration of structured EHR education to medical curricula can better prepare future physicians in managing information overload, improve diagnostic accuracy, and enhance the quality of patient care. Future research should explore the long-term impact of structured EHR training on clinical performance, diagnostic accuracy, and patient outcomes during real-world clinical placements and postgraduate training. Full article

(This article belongs to the Section Clinical Research Methods)

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12 pages, 1482 KiB

Open AccessEditor’s ChoiceArticle

Ophthalmic Artery Doppler Indices at 11–13 Weeks of Gestation in Relation to Early and Late Preeclampsia

by Nicoleta Gana, Savia Pittokopitou, Filippos Solonos, Alina Perdeica, Marina Fitiri and Kypros H. Nicolaides

J. Clin. Med. 2025, 14(13), 4811; https://doi.org/10.3390/jcm14134811 - 7 Jul 2025

Viewed by 715

Abstract

Background/Objective: Preeclampsia (PE) remains a leading cause of maternal and fetal morbidity and mortality. Early prediction is crucial for timely intervention and management. The ophthalmic artery (OA) Doppler assessment in the first trimester has emerged as a potential tool for predicting PE, particularly [...] Read more.

Background/Objective: Preeclampsia (PE) remains a leading cause of maternal and fetal morbidity and mortality. Early prediction is crucial for timely intervention and management. The ophthalmic artery (OA) Doppler assessment in the first trimester has emerged as a potential tool for predicting PE, particularly early PE, with delivery <37 weeks of gestation. This study aimed to evaluate and compare the relationship of ophthalmic artery Doppler parameters at 11–13 weeks of gestation with the subsequent development of early and late PE. Methods: A prospective observational analysis was conducted on 4054 pregnant women, including 114 who developed PE. OA Doppler assessment of the pulsatility index (PI) and peak systolic velocity (PSV) ratio, mean arterial pressure (MAP), uterine artery PI (UtA-PI), and serum placental growth factor (PlGF) were compared between women who later developed early PE and late PE with those who did not develop PE. Results: In the PE groups, particularly those with early PE, compared to the no PE group, the OA PSV ratio and UtA-PI were higher and PlGF was lower. Conclusion: A first-trimester OA Doppler assessment shows promise as a non-invasive method for the prediction of PE. Further prospective, multicenter studies are needed to validate these findings. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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21 pages, 1162 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Transthyretin Amyloid Cardiomyopathy—2025 Update: Current Diagnostic Approaches and Emerging Therapeutic Options

by Carsten Tschöpe, Ahmed Elsanhoury and Arnt V. Kristen

J. Clin. Med. 2025, 14(13), 4785; https://doi.org/10.3390/jcm14134785 - 7 Jul 2025

Viewed by 2260

Abstract

Transthyretin-related (ATTR) amyloidosis is a progressive, multisystem disease caused by the extracellular deposition of misfolded transthyretin (TTR) monomers as insoluble amyloid fibrils. Clinical manifestations vary widely and may include cardiomyopathy (ATTR-CM), polyneuropathy (ATTR-PN), or mixed phenotypes. The condition is increasingly recognized as an [...] Read more.

Transthyretin-related (ATTR) amyloidosis is a progressive, multisystem disease caused by the extracellular deposition of misfolded transthyretin (TTR) monomers as insoluble amyloid fibrils. Clinical manifestations vary widely and may include cardiomyopathy (ATTR-CM), polyneuropathy (ATTR-PN), or mixed phenotypes. The condition is increasingly recognized as an underdiagnosed contributor to heart failure, particularly in elderly patients. ATTR amyloidosis exists in two major forms: hereditary (ATTRv), resulting from mutations in the TTR gene, and wild-type (ATTRwt), typically affecting men over 70 years of age. Advances in disease understanding have led to a paradigm shift in management, with the introduction of targeted therapies that slow disease progression and improve prognosis. First-generation therapies such as tafamidis have demonstrated survival benefits in ATTR-CM. More recently, second-generation agents—such as the TTR stabilizer acoramidis and RNA silencers including vutrisiran and eplontersen—have shown promising efficacy in clinical trials. Additional strategies under investigation include gene editing and monoclonal antibodies targeting TTR amyloid deposits. This review outlines current diagnostic strategies and therapeutic options for ATTR amyloidosis, emphasizing the need for early detection and individualized treatment approaches. The expanding therapeutic landscape highlights the importance of accurate phenotyping and timely intervention to optimize clinical outcomes. Full article

(This article belongs to the Special Issue Cardiomyopathies: Current Treatment and Future Options: Second Edition)

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21 pages, 5728 KiB

Open AccessEditor’s ChoiceReview

Clinical Application of rhBMP-2 and Three-Dimensinal Preformed Titanium Mesh with Allograft and Xenograft for Peri-Implant Horizontal and Vertical Bone Augmentation–A Narrative Review with Technical Report

by Yeong Wook Kim, Saverio Cosola, Young Sam Kim, Young Min Park, Ugo Covani, Aimone Fabbri and Giovanni Battista Menchini-Fabris

J. Clin. Med. 2025, 14(13), 4788; https://doi.org/10.3390/jcm14134788 - 7 Jul 2025

Viewed by 586

Abstract

The reconstruction of a severely resorbed alveolar bone is a significant challenge in dental implantology and maxillofacial surgery. Traditional bone grafting materials, including autogenous, allogeneic, xenogeneic, and alloplastic materials, have limitations such as donor site morbidity, limited availability, and prolonged maturation periods. To [...] Read more.

The reconstruction of a severely resorbed alveolar bone is a significant challenge in dental implantology and maxillofacial surgery. Traditional bone grafting materials, including autogenous, allogeneic, xenogeneic, and alloplastic materials, have limitations such as donor site morbidity, limited availability, and prolonged maturation periods. To address these challenges, recombinant human bone morphogenetic protein-2 (rhBMP-2) has emerged as a potent osteoinductive factor that facilitates bone regeneration without the need for additional donor site surgery. This study introduces a box technique which combines rhBMP-2 (CowellBMP^®, Cowellmedi, Busan, Republic of Korea) with a 3D-preformed titanium mesh (3D-PFTM), utilizing a mixture of allografts and xenografts for horizontal and vertical alveolar ridge augmentation. The technique leverages the structural stability provided by the OssBuilder^® (Osstem, Seoul, Republic of Korea), a preformed titanium mesh, that allows for simultaneous implant placement and vertical ridge augmentation. This technique not only reduces the treatment time compared to traditional methods but also minimizes post-operative discomfort by eliminating the need for autogenous bone harvesting. Clinical outcomes from this technique demonstrate successful bone regeneration within a shorter period than previously reported techniques, with excellent bone quality and implant stability being observed just four months after vertical augmentation. In conclusion, the so called BOXAM (BMP-2, Oss-builder, Xenograft, Allograft, Maintenance) technique presents a promising therapeutic strategy for alveolar bone reconstruction, particularly in cases of severe bone resorption. Further studies are needed to evaluate the long-term outcomes and potential limitations of this approach, especially in scenarios where the inferior alveolar nerve proximity poses challenges for fixture placement. Full article

(This article belongs to the Special Issue Oral and Maxillofacial Surgery: Current Advances and Future Directions)

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13 pages, 1654 KiB

Open AccessEditor’s ChoiceArticle

Effect of Complete Revascularization in STEMI: Ischemia-Driven Rehospitalization and Cardiovascular Mortality

by Miha Sustersic and Matjaz Bunc

J. Clin. Med. 2025, 14(13), 4793; https://doi.org/10.3390/jcm14134793 - 7 Jul 2025

Viewed by 365

Abstract

Background: Patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD) who undergo complete revascularization (CR) have a more favorable prognosis than those who receive incomplete revascularization (IR), as evidenced by recent randomized controlled trials. Despite the absence of a [...] Read more.

Background: Patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD) who undergo complete revascularization (CR) have a more favorable prognosis than those who receive incomplete revascularization (IR), as evidenced by recent randomized controlled trials. Despite the absence of a survival benefit associated with CR in these trials, positive outcomes were ascribed to combined endpoints, such as repeat revascularization, myocardial infarction, or ischemia-driven rehospitalization. In light of the significant burden that rehospitalization from STEMI imposes on healthcare systems, we examined the long-term effects of CR on ischemia-driven rehospitalization and cardiovascular (CV) mortality in STEMI patients with MVD. Methods: In our retrospective study, we included patients with STEMI and MVD who underwent successful primary percutaneous coronary intervention (PCI) at the University Medical Centre Ljubljana between 1 January 2009, and 11 April 2011. The combined endpoint was ischemia-driven rehospitalization and CV mortality, with a minimum follow-up period of six years. Results: We included 235 participants who underwent CR (N = 70) or IR (N = 165) at index hospitalization, with a median follow-up time of 7 years (interquartile range 6.0–8.2). The primary endpoint was significantly higher in the IR group than in the CR group (47.3% vs. 32.9%, log-rank p = 0.025), driven by CV mortality (23.6% vs. 12.9%, log-rank p = 0.047), as there was no difference in ischemia-driven rehospitalization rate (log-rank p = 0.206). Ischemia-driven rehospitalization did not influence CV mortality in the CR group (p = 0.49), while it significantly impacted CV mortality in the IR group (p = 0.03). After adjusting for confounders, there were no differences in CV mortality between CR and IR groups (p = 0.622). Predictors of the combined endpoint included age (p = 0.014), diabetes (p = 0.006), chronic kidney disease (CKD) (p = 0.001), cardiogenic shock at presentation (p = 0.003), chronic total occlusion (CTO) (p = 0.046), and ischemia-driven rehospitalization (p = 0.0001). Significant risk factors for the combined endpoint were cardiogenic shock at presentation (p < 0.001), stage 4 kidney failure (p = 0.001), age over 70 years (p = 0.004), female gender (p = 0.008), and residual SYNTAX I score > 5.5 (p = 0.017). Conclusions: Patients with STEMI and MVD who underwent CR had a lower combined endpoint of ischemia-driven rehospitalizations and CV mortality than IR patients, but after adjustments for confounders, the true determinants of the combined endpoint and risk factors for the combined endpoint were independent of the revascularization method. Full article

(This article belongs to the Special Issue Acute Myocardial Infarction: Clinical Advances in Prognostic Stratification, Diagnosis, and Treatment)

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13 pages, 1778 KiB

Open AccessEditor’s ChoiceArticle

Association of Atrial Fibrillation with Incident Probable Dementia and Cognitive Impairment in the Systolic Blood Pressure Intervention Trial (SPRINT)

by Parham Samimisedeh, Richard Kazibwe, Christopher L. Schaich, Timothy M. Hughes and Elsayed Z. Soliman

J. Clin. Med. 2025, 14(13), 4791; https://doi.org/10.3390/jcm14134791 - 7 Jul 2025

Viewed by 462

Abstract

Background: The association between atrial fibrillation (AF) and dementia and cognitive decline in individuals with hypertension is not well established. Methods: The Systolic Blood Pressure Intervention Trial (SPRINT) enrolled participants with hypertension at high risk of cardiovascular disease (CVD) but without diabetes [...] Read more.

Background: The association between atrial fibrillation (AF) and dementia and cognitive decline in individuals with hypertension is not well established. Methods: The Systolic Blood Pressure Intervention Trial (SPRINT) enrolled participants with hypertension at high risk of cardiovascular disease (CVD) but without diabetes or a history of stroke. Participants with baseline pre-existing clinical dementia, prescribed dementia medications, or missing AF or cognition data were excluded. AF was identified using centrally read electrocardiograms. Mild cognitive impairment (MCI) and probable dementia (PD) were determined during follow-up by an adjudication committee. Multivariable Cox proportional hazards regression models were employed to assess the association of time-dependent AF with MCI, PD, and a composite endpoint of MCI/PDI. Results: A total of 8539 participants (mean age: 67.9 years; 35.1% female) were included in the analysis. Of these, 264 had AF at baseline or during follow-up. Over a median follow-up period of 5 years, 318 PD, 625 MCI, and 849 composite PD or MCI events occurred. In models adjusted for treatment assignment, baseline sociodemographics, CVD risk factors, and potential confounders, time-dependent AF was associated with incident PD, MCI, and a composite endpoint of MCI/PDI [HR (95% CI): 1.84 (1.09, 3.13), 1.59 (1.01, 2.53), and 1.63 (1.12, 2.38), respectively]. Further adjustment for incident stroke did not significantly change these associations. Conclusions: AF is associated with an increased risk of dementia and cognitive impairment in patients with hypertension but not diabetes or stroke. Further research is needed to determine whether AF management strategies can mitigate cognitive decline. Full article

(This article belongs to the Section Cardiology)

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18 pages, 587 KiB

Open AccessEditor’s ChoiceReview

The Role of C-Reactive Protein in Acute Myocardial Infarction: Unmasking Diagnostic, Prognostic, and Therapeutic Insights

by Andreas Mitsis, Stefanos Sokratous, Georgia Karmioti, Michaela Kyriakou, Michail Drakomathioulakis, Michael M. Myrianthefs, Christos Eftychiou, Nikolaos P. E. Kadoglou, Stergios Tzikas, Nikolaos Fragakis and George Kassimis

J. Clin. Med. 2025, 14(13), 4795; https://doi.org/10.3390/jcm14134795 - 7 Jul 2025

Viewed by 917

Abstract

C-reactive protein (CRP) has emerged as a valuable biomarker in acute myocardial infarction (AMI), offering multiple insights into diagnosis, prognosis, and therapeutic strategies. In the diagnostic domain, elevated CRP levels serve as an early indicator of AMI, aiding in prompt identification and initiation [...] Read more.

C-reactive protein (CRP) has emerged as a valuable biomarker in acute myocardial infarction (AMI), offering multiple insights into diagnosis, prognosis, and therapeutic strategies. In the diagnostic domain, elevated CRP levels serve as an early indicator of AMI, aiding in prompt identification and initiation of treatment. Prognostically, CRP is a strong predictor of adverse outcomes post-AMI, correlating with increased mortality and cardiovascular events. Beyond its diagnostic and prognostic roles, CRP also exposes therapeutic avenues in AMI management. Targeting CRP through pharmacological interventions has shown promise in reducing inflammatory responses, thereby mitigating myocardial damage and improving clinical outcomes. However, CRP’s low specificity, influenced by elevation in non-cardiac conditions, remains a clinical limitation that warrants consideration. This review comprehensively examines the evolving role of CRP in AMI, exploring its diagnostic accuracy, prognostic significance, and potential as a therapeutic target. The understanding of the complex role of CRP in AMI provides clinicians with valuable tools for risk stratification, treatment optimization, and personalized patient care in the acute setting. Full article

(This article belongs to the Special Issue Acute Coronary Syndromes: From Diagnosis to Treatment)

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20 pages, 653 KiB

Open AccessEditor’s ChoiceArticle

Prophylactic Intra-Aortic Balloon Pump Implantation Reduces Peri-Interventional Myocardial Injury During High-Risk Percutaneous Coronary Intervention in Patients Presenting with Low Normal Blood Pressure and with Heart Failure

by Sascha d’Almeida, Stefanie Andreß, Sebastian Weinig, Benjamin Mayer, Wolfgang Rottbauer, Sinisa Markovic and Dominik Buckert

J. Clin. Med. 2025, 14(13), 4796; https://doi.org/10.3390/jcm14134796 - 7 Jul 2025

Viewed by 506

Abstract

Background: Intra-aortic balloon pump (IABP) augments coronary perfusion during high-risk percutaneous coronary interventions (PCI). We sought to identify patients who benefited from prophylactic IABP (P-IABP) compared to rescue-IABP (R-IABP). Methods: All consecutive non-cardiogenic shock patients undergoing high-risk PCI with IABP support [...] Read more.

Background: Intra-aortic balloon pump (IABP) augments coronary perfusion during high-risk percutaneous coronary interventions (PCI). We sought to identify patients who benefited from prophylactic IABP (P-IABP) compared to rescue-IABP (R-IABP). Methods: All consecutive non-cardiogenic shock patients undergoing high-risk PCI with IABP support at Ulm University Hospital, Germany, between 2012 and 2020 were grouped based on the timing of IABP insertion in the pre-interventional P-IABP or peri-interventional R-IABP group. We compared the primary endpoint peri-interventional high-sensitivity Troponin T (hsTnT) increase, sought baseline characteristics associated with the endpoint in the R-IABP group, and compared their correlation strengths between the groups. Results: Interventional outcomes of 44 patients with P-IABP implantation were compared with those of 15 patients with R-IABP implantation. P-IABP was associated with a lower peri-interventional hsTnT increase (p = 0.008, r = 0.390). In the R-IABP group, the presence of ST-segment elevation (p = 0.037, r = 0.631), low systolic blood pressure (RRsyst) (p = 0.007, r = 0.893 (inverse correlation)), and elevated NT-proBNP levels (p < 0.001, r = 0.953) were associated with higher hsTnT increases. HsTnT increase was significantly smaller in the P-IABP group in patients with low RRsyst (IZI = 2.6) and high NT-proBNP levels (IZI = 3.36). Patients with RRsyst < 120 mmHg (p = 0.007) and NT-proBNP levels ≥ 900 pg/mL (Cohen’s d = 0.70, respectively 1.17 for ≥5000 pg/mL and 5.01 for ≥10,000 pg/mL) showed lower peri-interventional hsTnT increase when treated with P-IABP compared to R-IABP, while patients with NT-proBNP levels < 900 pg/mL showed a contrary effect (Cohen’s d = −0.90). Cox regression analysis showed that a high peri-interventional hsTnT increase was significantly associated with a shorter survival time (p = 0.046). Conclusions: P-IABP use in high-risk PCI was associated with reduced peri-interventional myocardial injury, as measured by lower hsTnT increase, which was associated with improved survival in patients with low systolic blood pressure and elevated NT-proBNP levels. Thus, these conditions should be considered for indicating P-IABP. Full article

(This article belongs to the Special Issue Clinical Management for Coronary Artery Disease and Revascularization)

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15 pages, 1910 KiB

Open AccessEditor’s ChoiceSystematic Review

Training Interventions Used in Postmenopausal Women to Improve Pelvic Floor Muscle Function Related to Urinary Continence—A Systematic Review

by Magdalena Piernicka, Justyna Labun and Anna Szumilewicz

J. Clin. Med. 2025, 14(13), 4800; https://doi.org/10.3390/jcm14134800 - 7 Jul 2025

Viewed by 819

Abstract

Background: The aim of this review was to analyze training interventions used and their effectiveness in improving pelvic floor muscle function related to urinary continence in postmenopausal women. We then characterized the recommended pelvic floor muscle training programs used in experimental studies based [...] Read more.

Background: The aim of this review was to analyze training interventions used and their effectiveness in improving pelvic floor muscle function related to urinary continence in postmenopausal women. We then characterized the recommended pelvic floor muscle training programs used in experimental studies based on four training components: frequency, intensity, duration, and type of pelvic floor muscle exercise. Methods: For this purpose, we conducted a literature review of works published up until the end of 2024, available in the Web of Science, PubMed, MEDLINE, and SPORTDiscus with Full Text databases. We used the keywords “pelvic floor muscle”, “training”, and “postmenopausal women”. Initially, we identified 205 articles published between 1997 and 2024. Then, based on specific criteria, we qualified 15 for analysis. Results: Thirteen studies included only PFMT, while three of them combined PFMT with other physical activity. In two studies, training was conducted in the form of a virtual video game using a pressure platform. We have noted that researchers most often use a 1 h pad test, digital palpation, and surface electromyography to assess the function of pelvic floor muscles. In improving pelvic floor muscle function related to urinary incontinence, 14 out of the 15 analyzed studies showed improvement. In only eight of the fifteen articles, researchers characterized all components of the implemented PFMT that enable full replication of the training intervention. In four of the studies, only one of the required components, namely intensity, was missing. The recommended number of training sessions was 2 to 7 per week, on average 3 ± 2 (M ± SD). Training interventions lasted from 2 to 24 weeks, on average 10 ± 6 weeks. Conclusions: Regardless of the chosen form of training intervention, PFMT is an effective method in improving the function of pelvic floor muscles in postmenopausal women. Full article

(This article belongs to the Section Sports Medicine)

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13 pages, 237 KiB

Open AccessEditor’s ChoiceArticle

Can Adjunctive Lithium Therapy Influence Emotional Dysregulation in Adolescents? Findings from a Retrospective Study

by Federica Gigliotti, Luca Cammisa, Sara Riezzo and Arianna Terrinoni

J. Clin. Med. 2025, 14(13), 4807; https://doi.org/10.3390/jcm14134807 - 7 Jul 2025

Viewed by 395

Abstract

Background: Emotional dysregulation (ED) is a transdiagnostic feature of multiple adolescent psychiatric disorders and a predictor of functional impairment and self-harming behaviors. Despite its clinical relevance, pharmacological treatments targeting ED in youth remain underexplored. This retrospective study investigated the clinical effectiveness and [...] Read more.

Background: Emotional dysregulation (ED) is a transdiagnostic feature of multiple adolescent psychiatric disorders and a predictor of functional impairment and self-harming behaviors. Despite its clinical relevance, pharmacological treatments targeting ED in youth remain underexplored. This retrospective study investigated the clinical effectiveness and tolerability of adjunctive lithium therapy in adolescents with severe ED, independent of specific diagnostic categories. Methods: A total of 35 inpatients (13–17 years) with significant ED were divided into two groups based on pharmacological treatment: lithium add-on therapy (Li group, n = 17) and standard therapy without lithium (Control group, n = 18). Clinical severity (CGI-S) and global functioning (C-GAS) were assessed at baseline (T0), 6 months (T1), and 12 months (T2). A mixed-design ANOVA was performed to assess group × time interactions. Adverse events and treatment adherence were also examined. Results: At T1, the Li group showed a significantly greater reduction in symptom severity (CGI-S) compared to the Control group (p = 0.029). Global functioning (C-GAS) improved over time in both groups (p < 0.001), with no significant interaction effects. Adverse effects, primarily metabolic and endocrine, were more frequent in the Li group but did not reduce adherence. Conclusions: Adjunctive lithium therapy may reduce symptom severity in adolescents with severe ED without negatively affecting treatment tolerability or adherence. These findings support the potential utility of lithium in complex adolescent cases and warrant further prospective research. Full article

(This article belongs to the Section Mental Health)

16 pages, 1640 KiB

Open AccessEditor’s ChoiceReview

Hepatitis C—Everything a Primary Care Physician Needs to Know About Diagnosis, Management, and Follow-Up

by Sindhuri Benjaram, Shweta Kapur, Anusha McKay, Mohamad Khaled Almujarkesh, Kassandra S. Carter, Alexandra Picardal, Diane Levine and Prateek Lohia

J. Clin. Med. 2025, 14(13), 4801; https://doi.org/10.3390/jcm14134801 - 7 Jul 2025

Viewed by 592

Abstract

Hepatitis C virus (HCV) infection is a major public health concern, with more than 58 million people chronically infected worldwide. The management of HCV, once the domain of specialists only, has been revolutionized by the advent of direct-acting antiviral therapies. To reduce the [...] Read more.

Hepatitis C virus (HCV) infection is a major public health concern, with more than 58 million people chronically infected worldwide. The management of HCV, once the domain of specialists only, has been revolutionized by the advent of direct-acting antiviral therapies. To reduce the burden of HCV in the United States (US), emphasis is now being placed on the involvement of primary care physicians in the management of HCV patients. Inclusion of more primary care providers in the HCV diagnosis and treatment initiatives can assist in achieving the goal of HCV elimination, especially in the medically underserved areas. To actively engage in the management of HCV, primary care providers must understand its epidemiology, risk factors, natural history, current treatment regimen, and potential complications. This manuscript reviews these key areas, along with presenting the cost-effectiveness of treatment and evidence-based guidelines for follow-up care in adults with chronic HCV infection who have undergone HCV treatment. Equipped with this foundational knowledge about HCV management, primary care physicians can play a vital role in eliminating HCV. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

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22 pages, 5786 KiB

Open AccessEditor’s ChoiceReview

Narrative and Pictorial Review on State-of-the-Art Endovascular Treatment for Focal Non-Infected Lesions of the Abdominal Aorta: Anatomical Challenges, Technical Solutions, and Clinical Outcomes

by Mario D’Oria, Marta Ascione, Paolo Spath, Gabriele Piffaretti, Enrico Gallitto, Wassim Mansour, Antonino Maria Logiacco, Giovanni Badalamenti, Antonio Cappiello, Giulia Moretti, Luca Di Marzo, Gianluca Faggioli, Mauro Gargiulo and Sandro Lepidi

J. Clin. Med. 2025, 14(13), 4798; https://doi.org/10.3390/jcm14134798 - 7 Jul 2025

Viewed by 572

Abstract

The natural history of focal non-infected lesions of the abdominal aorta (fl-AA) remains unclear and largely depends on their aetiology. These lesions often involve a focal “tear” or partial disruption of the arterial wall. Penetrating aortic ulcers (PAUs) and intramural hematomas (IMHs) are [...] Read more.

The natural history of focal non-infected lesions of the abdominal aorta (fl-AA) remains unclear and largely depends on their aetiology. These lesions often involve a focal “tear” or partial disruption of the arterial wall. Penetrating aortic ulcers (PAUs) and intramural hematomas (IMHs) are examples of focal tears in the aortic wall that can either progress to dilatation (saccular aneurysm) or fail to fully propagate through the medial layers, potentially leading to aortic dissection. These conditions typically exhibit a morphology consistent with eccentric saccular aneurysms. The management of focal non-infected pathologies of the abdominal aorta remains a subject of debate. Unlike fusiform abdominal aortic aneurysms, the inconsistent definitions and limited information regarding the natural history of saccular aneurysms (sa-AAAs) have prevented the establishment of universally accepted practice guidelines for their management. As emphasized in the latest 2024 ESVS guidelines, the focal nature of these diseases makes them ideal candidates for endovascular repair (class of evidence IIa—level C). Moreover, the Society for Vascular Surgery just referred to aneurysm diameter as an indication for treatment suggesting using a smaller diameter compared to fusiform aneurysms. Consequently, the management of saccular aneurysms is likely heterogeneous amongst different centres and different operators. Endovascular repair using tube stent grafts offers benefits like reduced recovery times but carries risks of migration and endoleak due to graft rigidity. These complications can influence long-term success. In this context, the use of endovascular bifurcated grafts may provide a more effective solution for treating these focal aortic pathologies. It is essential to achieve optimal sealing regions through anatomical studies of aortic morphology. Additionally, understanding the anatomical characteristics of focal lesions in challenging necks or para-visceral locations is indeed crucial in device choice. Off-the-shelf devices are favoured for their time and cost efficiency, but new endovascular technologies like fenestrated endovascular aneurysm repair (FEVAR) and custom-made devices enhance treatment success and patient safety. These innovations provide stent grafts in various lengths and diameters, accommodating different aortic anatomies and reducing the risk of type III endoleaks. Although complicated PAUs and focal saccular aneurysms rarely arise in the para-visceral aorta, the consequences of rupture in this segment might be extremely severe. Experience borrowed from complex abdominal and thoracoabdominal aneurysm repair demonstrates that fenestrated and branched devices can be deployed safely when anatomical criteria are respected. Elective patients derive the greatest benefit from a fenestrated graft, while urgent cases can be treated confidently with off-the-shelf multibranch systems, reserving other types of repairs for emergent or bail-out cases. While early outcomes of these interventions are promising, it is crucial to acknowledge that limited aortic coverage can still impede effective symptom relief and lead to complications such as aneurysm expansion or rupture. Therefore, further long-term studies are essential to consolidate the technical results and evaluate the durability of various graft options. Full article

(This article belongs to the Special Issue Clinical Advances in Aortic Disease and Revascularization)

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13 pages, 1719 KiB

Open AccessEditor’s ChoiceArticle

Radiomics Models to Predict Tumor Response and Pneumonitis in Non-Small Cell Lung Cancer Patients Treated with Immunotherapy

by Monica Yadav, Wongi Woo, Young Kwang Chae, Jeeyeon Lee, Peter Haseok Kim, Seyoung Lee, Taegyu Um, Salie Lee, Maria Jose Aguilera Chuchuca, Trie Arni Djunadi, Liam Il-Young Chung, Jisang Yu, Nicolo Gennaro, Leeseul Kim, Myungwoo Nam, Youjin Oh, Sungmi Yoon, Zunairah Shah, Yuchan Kim, Ilene Hong, Jessica Jang, Grace Kang, Amy Cho, Soowon Lee, Timothy Hong, Cecilia Nam and Yury S. Velichko Show full author list Hide full author list

J. Clin. Med. 2025, 14(12), 4330; https://doi.org/10.3390/jcm14124330 - 18 Jun 2025

Viewed by 1903

Abstract

Background: Checkpoint inhibitor-associated pneumonitis (CIP) after immunotherapy has become a challenging issue in non-small cell lung cancer (NSCLC) patients. This study leverages artificial intelligence (AI) algorithms to analyze radiomic features, aiming to predict the occurrence of CIP, as well as tumor response. Methods: [...] Read more.

Background: Checkpoint inhibitor-associated pneumonitis (CIP) after immunotherapy has become a challenging issue in non-small cell lung cancer (NSCLC) patients. This study leverages artificial intelligence (AI) algorithms to analyze radiomic features, aiming to predict the occurrence of CIP, as well as tumor response. Methods: This study analyzed data from 159 stage III-IV NSCLC patients undergoing immunotherapy. The patients were categorized into pneumonitis and non-pneumonitis groups, and 3D radiomic features from both tumors and surrounding regions were extracted using LIFEx software. To address scanner-associated variations, a linear mixed-effect radiomics harmonization model was applied. A random forest algorithm was then used to develop models predicting CIP occurrence and tumor responses based on the pre-treatment CT radiomics. The accuracy was evaluated using the area under the curve (AUC). Results: A total of 159 patients were analyzed, of which only 31 experienced CIP. Most had grade 1 (17/31, 54.8%) or 2 (12/31, 38.7%) pneumonitis; only two (6.5%) patients had grade 3. Patients who developed pneumonitis were more likely to be male (64.5% vs. 38.3%, p = 0.014), had less adenocarcinoma histology (54.8% vs. 78.9%, p = 0.032), and exhibited a higher tumor mutational burden (57.1% vs. 24.5%, p = 0.047). Radiomics analysis reported predictability for CIP with an AUC of 0.60 (95% CI 0.55–0.66). The five-year overall and progression-free survival rates were 24.7% (95% CI 15.2–35.5%) and 9.7% (95% CI 4.4–17.4%), respectively. The radiomics features also exhibited AUCs of 0.63 (95% CI 0.59–0.67) in irRECIST and 0.66 (95% CI 0.61–0.70) in RECIST 1.1 in terms of tumor responses to immunotherapy. Conclusions: This study provides insights into the potential role of radiomic models in predicting CIP and tumor responses from pre-treatment CT images of NSCLC patients treated with immunotherapy. Full article

(This article belongs to the Section Oncology)

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20 pages, 1678 KiB

Open AccessEditor’s ChoiceReview

Surgical Strategies and Challenges in Scheuermann’s Kyphosis: A Comprehensive Review

by Angelos Kaspiris, Ioannis Spyrou, Fotios Panagopoulos, Vasileios Marougklianis, Periklis Pelantis, Michail Vavourakis, Evangelos Sakellariou, Ioanna Lianou, Dimitrios Ntourantonis, Thomas Repantis, Elias S. Vasiliadis and Spiros G. Pneumaticos

J. Clin. Med. 2025, 14(12), 4276; https://doi.org/10.3390/jcm14124276 - 16 Jun 2025

Viewed by 2404

Abstract

Background: Scheuermann’s kyphosis (SK) is characterized by anterior wedging of >5 degrees at three or more contiguous vertebrae associated with severe back pain and cosmetic disfigurement. Different surgical interventions have been applied for SK correction, but the optimal operational treatment remains controversial. [...] Read more.

Background: Scheuermann’s kyphosis (SK) is characterized by anterior wedging of >5 degrees at three or more contiguous vertebrae associated with severe back pain and cosmetic disfigurement. Different surgical interventions have been applied for SK correction, but the optimal operational treatment remains controversial. Objectives: The aim of our study is to analyze all the current indications for the surgical correction of SK, as well as to describe the instrumentation methods and techniques in order to detect the ideal operational management and accompanied complications. Methods: This comprehensive review investigates the up-to-date surgical indications and approaches for SK, the current trends, and the associated postoperative functional outcomes. A detailed search of PubMed, Web of Science and Google Scholar databases in English literature was performed for articles during the last 20 years. Additional criteria were peer-reviewed original studies that provided the type of interventions for SK and the clinical outcomes. Results: Thirty studies that met our induction criteria were analyzed. The up-to-date surgical indications such as back pain, failure of conservative treatment, progression of deformity, and neurological complications were described. Anterior (AO) and posterior-only (PO), and combined anterior–posterior (AP) approaches and instrumentation techniques were outlined. The most common side effects of the above interventions were hardware failure, loss of correction and Proximal Junctional Kyphosis. Contrariwise, in PO, reduced blood loss and operational duration was noted. Conclusions: Although the published studies reported contradictory results of the effectiveness of the various techniques applied for SK treatment, the PO fusion was correlated with a decreased rate of complications that resulted in its current increase in popularity. Full article

(This article belongs to the Special Issue Clinical New Insights into Management of Scoliosis)

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28 pages, 1776 KiB

Open AccessEditor’s ChoiceReview

Nutrition and Diet Patterns as Key Modulators of Metabolic Reprogramming in Melanoma Immunotherapy

by Katerina Grafanaki, Alexandros Maniatis, Alexandra Anastogianni, Angelina Bania, Efstathia Pasmatzi and Constantinos Stathopoulos

J. Clin. Med. 2025, 14(12), 4193; https://doi.org/10.3390/jcm14124193 - 12 Jun 2025

Viewed by 2837

Abstract

Background: Melanoma, one of the most aggressive forms of skin cancer, has seen significant therapeutic advances with immune checkpoint inhibitors (ICIs). However, many patients fail to respond or develop resistance, creating the need for adjunct strategies. Objective: The objective of this [...] Read more.

Background: Melanoma, one of the most aggressive forms of skin cancer, has seen significant therapeutic advances with immune checkpoint inhibitors (ICIs). However, many patients fail to respond or develop resistance, creating the need for adjunct strategies. Objective: The objective of this study is to critically evaluate how specific dietary patterns and nutrient-derived metabolites modulate melanoma metabolism and immunotherapy outcomes, emphasizing translational implications. Methods: We performed an integrative review of preclinical and clinical studies investigating dietary interventions in melanoma models and ICI-treated patients. Mechanistic insights were extracted from studies on nutrient transport, immunometabolism, and microbiome–immune interactions, including data from ongoing nutritional clinical trials. Results: Diets rich in fermentable fibers, plant polyphenols, and unsaturated lipids, such as Mediterranean and ketogenic diets, seem to contribute to the reprogramming of tumor metabolism and enhance CD8+ T-cell activity. Fasting-mimicking and methionine-restricted diets modulate T-cell fitness and tumor vulnerability via nutrient stress sensors (e.g., UPR, mTOR). High fiber intake correlates with favorable gut microbiota and improved ICI efficacy, while excess protein, methionine, or refined carbohydrates impair immune surveillance via lactate accumulation and immunosuppressive myeloid recruitment. Several dietary molecules act as network-level modulators of host and microbial proteins, with parallels to known drug scaffolds. Conclusions: Integrating dietary interventions into melanoma immunotherapy can significantly influence metabolic reprogramming by targeting metabolic vulnerabilities and reshaping the tumor–immune–microbiome axis. When combined with AI-driven nutrient–protein interaction mapping, this approach offers a precision nutrition paradigm that supports both physicians and patients, emerging as a novel layer to enhance and consolidate existing therapeutic strategies. Full article

(This article belongs to the Section Clinical Nutrition & Dietetics)

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14 pages, 1247 KiB

Open AccessEditor’s ChoiceArticle

The Core of the Issue: Plank Performance and Pain in the Lower Back

by Kira Eimiller, Leann LeFevre, Catherine Robarge, Cara Strano, Kelsey Tarbrake and Isabelle Wittmann

J. Clin. Med. 2025, 14(11), 3926; https://doi.org/10.3390/jcm14113926 - 3 Jun 2025

Viewed by 3525

Abstract

Background and Objectives: Low back pain (LBP) is a leading cause of disability worldwide. Core stabilization exercises such as the plank are often prescribed in rehabilitation settlings to improve neuromuscular control and spinal support. However, it remains unclear whether plank performance -accurately [...] Read more.

Background and Objectives: Low back pain (LBP) is a leading cause of disability worldwide. Core stabilization exercises such as the plank are often prescribed in rehabilitation settlings to improve neuromuscular control and spinal support. However, it remains unclear whether plank performance -accurately reflects trunk function or disability in individuals with LBP. The purpose of this study was to evaluate the relationship between plank endurance and low back pain in adults. Methods: A cross-sectional study was conducted with 117 adults aged 20–61 years (mean 26.0 ± 9.3), including both individuals with and without LBP. Participants completed a plank endurance test and the Modified Oswestry Disability Index (MODI). A subset of fifty-four participants with LBP also completed single-leg bridge tests to assess posterior chain endurance. Statistical analyses included Mann–Whitney U tests to compare plank times by LBP status, logistic regression to evaluate predictors of LBP, and correlation analyses to examine associations between the bridge-to-plank ratio and MODI scores. Results: Contrary to the initial hypothesis, individuals with LBP demonstrated significantly longer plank hold times than those without (U = 1861.00, p = 0.036). Logistic regression indicated that the overall model was statistically significant (χ² = 12.39, p = 0.030), but plank duration was not an independent predictor of LBP (p = 0.070). Among participants with LBP, a higher bridge-to-plank ratio, reflecting relatively greater posterior chain endurance, was significantly associated with lower disability scores (Pearson r = −0.31, p = 0.023; Spearman ρ = −0.32, p = 0.018). Conclusions: These findings suggest that, while plank duration differs by LBP status, longer plank times may not indicate lower risk or severity of back pain. A greater balance of posterior chain to anterior core endurance may be more intricately linked to reduced disability, highlighting the importance of comprehensive core assessment and training strategies in rehabilitation. Full article

(This article belongs to the Section Orthopedics)

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15 pages, 1280 KiB

Open AccessEditor’s ChoiceReview

Now and the Future: Medications Changing the Landscape of Cardiovascular Disease and Heart Failure Management

by Thomas Oswald, Steven Coombs, Susan Ellery and Alexander Liu

J. Clin. Med. 2025, 14(11), 3948; https://doi.org/10.3390/jcm14113948 - 3 Jun 2025

Cited by 1 | Viewed by 5210

Abstract

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. Epidemiological data demonstrate that the overlap between CVD, Type 2 Diabetes (T2DM), chronic kidney disease (CKD) and heart failure (HF) is becoming increasingly apparent, with aging populations making these patient cohorts [...] Read more.

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. Epidemiological data demonstrate that the overlap between CVD, Type 2 Diabetes (T2DM), chronic kidney disease (CKD) and heart failure (HF) is becoming increasingly apparent, with aging populations making these patient cohorts more difficult to treat. In the last decade, three standout drug classes have emerged with the potential to broaden the treatment options for patients with multi-morbid CVD and heart failure. These are sodium–glucose cotransporter 2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (MRAs), e.g., Finerenone, and glucagon-like peptide 1 receptor agonists (GLP-1RAs). These medications are now entering UK and European guidelines for the treatment of CVDs including HF whilst crucially providing associated prognostic benefits for patients with T2DM and CKD. The future of these agents for CVD risk stratification may involve primary care at the forefront, alongside tailored, patient-specific medication regimens. This review article aims to discuss these three main drug classes (SGLT2 inhibitors, GLP-1RAs and non-steroidal MRAs) in detail by exploring their current evidence base across heart failure (HF) and CVD management and future clinical implications of their usage as mainstream medical therapies. Full article

(This article belongs to the Special Issue What’s New in Cardiomyopathies: Diagnosis, Treatment and Management)

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18 pages, 777 KiB

Open AccessEditor’s ChoiceSystematic Review

Short-Term Effects of Spinal Manual Therapy on the Nervous System in Managing Musculoskeletal Pain: A Systematic Review

by Chloé Jupin, Vicente Beltran Aibar and François-Régis Sarhan

J. Clin. Med. 2025, 14(11), 3830; https://doi.org/10.3390/jcm14113830 - 29 May 2025

Viewed by 2397

Abstract

Background: Spinal manual therapy (SMT) is widely used in the management of musculoskeletal pain. In addition to mechanical effects, SMT may induce neurophysiological changes at both central and autonomic levels. However, the extent and consistency of these short-term effects remain unclear. Objective [...] Read more.

Background: Spinal manual therapy (SMT) is widely used in the management of musculoskeletal pain. In addition to mechanical effects, SMT may induce neurophysiological changes at both central and autonomic levels. However, the extent and consistency of these short-term effects remain unclear. Objective: To systematically review the short-term effects of SMT on pain perception, central nervous system (CNS) activity, and autonomic nervous system (ANS) responses in adults with musculoskeletal pain or in healthy controls. Methods: A systematic review was conducted. Three databases (PubMed, ScienceDirect, Embase) were searched up to October 2023, with a final update in March 2025. Randomized controlled trials involving SMT and assessing outcomes related to pain, CNS, or ANS function were included. The methodological quality was assessed using the PEDro scale. The results were synthesized narratively and categorized by outcome domain. Four summary tables were created to present the study characteristics, main findings, methodological quality, and risk of bias. Results: Eleven trials were included. SMT produced variable effects on pain perception, with more consistent results observed when the treatment was applied frequently and followed standardized protocols. The CNS-related outcomes (e.g., fMRI connectivity, motor-evoked potentials) suggested short-term modulation of brain and spinal excitability in some studies. The ANS responses were heterogeneous, ranging from parasympathetic activation to sympathetic stimulation, depending on the intervention and population. The methodological quality was moderate to high in most studies, although the small sample sizes and limited blinding increased the risk of bias. The effect sizes were not consistently reported. Conclusions: SMT may induce short-term neuromodulatory effects on pain, CNS, and ANS activity. These effects appear to be context-dependent and require precise, repeated, and purposeful application. Full article

(This article belongs to the Special Issue Physical Therapy in Musculoskeletal Disorders: Prevention, Diagnosis, Clinical Management and Treatment)

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13 pages, 773 KiB

Open AccessEditor’s ChoiceReview

Long-Term Antithrombotic Therapy in Patients with Atrial Fibrillation and Percutaneous Coronary Intervention

by Antonio Capolongo, Vincenzo De Sio, Felice Gragnano, Mattia Galli, Natale Guarnaccia, Pasquale Maddaluna, Giuseppe Verde, Vincenzo Acerbo, Pierre Sabouret, Daniele Giacoppo, Matteo Conte, Silvio Coletta, Vincenzo Diana, Michelangelo Luciani, Elisabetta Moscarella, Arturo Cesaro, Francesco Pelliccia and Paolo Calabrò

J. Clin. Med. 2025, 14(11), 3713; https://doi.org/10.3390/jcm14113713 - 26 May 2025

Viewed by 2504

Abstract

The optimal long-term antithrombotic treatment of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remains controversial. Current guidelines recommend a short initial period of triple antithrombotic therapy (e.g., 1 week), followed by dual therapy consisting of an oral anticoagulation agent and [...] Read more.

The optimal long-term antithrombotic treatment of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remains controversial. Current guidelines recommend a short initial period of triple antithrombotic therapy (e.g., 1 week), followed by dual therapy consisting of an oral anticoagulation agent and a single antiplatelet agent for 6 months in patients undergoing elective PCI and 12 months in patients with acute coronary syndromes. After this course of combination therapy, anticoagulation monotherapy is recommended. In daily practice, however, the optimal strategy for long-term antithrombotic therapy remains debated. A growing body of evidence supports the safety and efficacy of oral anticoagulation monotherapy, but its use in clinical practice remains inconsistent. This review aims to evaluate the available evidence on chronic antithrombotic regimens in patients with AF undergoing PCI, with a focus on key clinical considerations, such as the selection of optimal long-term therapy that balances ischemic and bleeding risks. It also highlights that, despite robust supporting evidence, significant gaps persist in real-world implementation. Full article

(This article belongs to the Special Issue Atrial Fibrillation and Its Complications: Preventive Strategies and Relative Evidence)

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11 pages, 626 KiB

Open AccessEditor’s ChoiceArticle

Incidence and Risk Factors for Incisional Hernia Following Ileostomy Takedown: A Retrospective Cohort Study

by Tamás Talpai, Flaviu-Ionuţ Faur, Cătălin-Alexandru Pîrvu, Daniela Marinescu, Cristi Tarta, Dragos Nicolae Margaritescu, Stelian Pantea, Cristian Nica, Rãzvan-Sorin Albu, Tudor-Alexandru Popoiu, Razvan Lazea, Larisa Balanoiu and Valeriu Șurlin

J. Clin. Med. 2025, 14(10), 3597; https://doi.org/10.3390/jcm14103597 - 21 May 2025

Viewed by 3289

Abstract

Background: Incisional hernias are a frequent complication following ileostomy closure, with rates reaching 24%. Protective ileostomies are commonly performed in colorectal surgery, but their closure presents a significant risk for abdominal wall defects. Identifying risk factors for incisional hernias at the ileostomy [...] Read more.

Background: Incisional hernias are a frequent complication following ileostomy closure, with rates reaching 24%. Protective ileostomies are commonly performed in colorectal surgery, but their closure presents a significant risk for abdominal wall defects. Identifying risk factors for incisional hernias at the ileostomy site is crucial for improving patient outcomes. Methods: This retrospective study analyzed data from 95 patients who underwent loop ileostomy closure at two Romanian hospitals between 2018 and 2023. Patient demographics, surgical details, and follow-up data were reviewed. Incisional hernias were diagnosed through clinical examination or radiological imaging. Statistical analyses, including univariate and multivariate regression, were performed to identify independent risk factors. Results: The incidence of incisional hernias at the ileostomy site was 13.7% (13/95). Univariate analysis identified BMI (HR 30.08; p = 0.007), previous hernia (HR 7.99; p = 0.059), radiotherapy (HR 299.15; p = 0.029), and chemotherapy (HR 0.004; p = 0.026) as significant factors. Multivariate analysis confirmed BMI > 30 kg/m² (HR 12.27; p = 0.002) and prior hernia (HR 8.14; p = 0.007) as independent risk factors. Conclusions: Obesity and previous hernias significantly increase the risk of incisional hernias following ileostomy closure. Radiological follow-up enhances early detection, and further studies should explore the benefits of prophylactic mesh reinforcement. Optimizing patient selection and surgical technique may reduce postoperative hernia rates, improving long-term outcomes. Full article

(This article belongs to the Special Issue Hernia Surgery and Postoperative Management)

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15 pages, 304 KiB

Open AccessEditor’s ChoiceReview

Is Targeting LDL-C Levels Below 70 mg/dL Beneficial for Cardiovascular and Overall Health? A Critical Examination of the Evidence

by Folkert H. van Bruggen and David M. Diamond

J. Clin. Med. 2025, 14(10), 3569; https://doi.org/10.3390/jcm14103569 - 20 May 2025

Viewed by 9972

Abstract

Over the past two decades, cardiovascular disease (CVD) prevention guidelines have progressively lowered LDL-C targets to <70 mg/dL for high-risk individuals based on the assumption of a linear relationship between LDL-C levels and CVD risk. However, the available evidence challenges this premise. Multiple [...] Read more.

Over the past two decades, cardiovascular disease (CVD) prevention guidelines have progressively lowered LDL-C targets to <70 mg/dL for high-risk individuals based on the assumption of a linear relationship between LDL-C levels and CVD risk. However, the available evidence challenges this premise. Multiple studies demonstrate a weak or inconsistent association between LDL-C levels and atherosclerosis progression at the individual patient-level. Systematic reviews supporting the linearity assumption have notable limitations, including extrapolation beyond observed LDL-C ranges and potential ecological fallacy, as meta-regression analyses rely on study-level data, while patient-level data within the same trials often show no association between LDL-C reduction and CVD outcomes. Moreover, randomized controlled trials explicitly designed to assess LDL-C targets have yielded inconclusive and biased results. LDL-C itself is a heterogeneous marker, with particle size and composition influencing its atherogenicity. The cardiovascular benefits of lipid-lowering therapies may arise in part from pleiotropic effects unrelated to LDL-C lowering. Additionally, several studies indicate that higher LDL-C levels are paradoxically associated with longevity in elderly populations that is equal to or even greater than that of the general population. Collectively, this body of evidence raises questions about the validity of current LDL-C targets < 70 mg/dL in high-risk patients. Full article

(This article belongs to the Section Cardiovascular Medicine)

30 pages, 1790 KiB

Open AccessEditor’s ChoiceReview

Finerenone: Potential Clinical Application Across the Spectrum of Cardiovascular Disease and Chronic Kidney Disease

by Nowreen Haq, Pulkita Uppal, Taslova Abedin and Anuradha Lala

J. Clin. Med. 2025, 14(9), 3213; https://doi.org/10.3390/jcm14093213 - 6 May 2025

Viewed by 4891

Abstract

Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD) and is a risk factor for progression to end-stage kidney disease and cardiovascular morbidity and mortality. Despite pharmacologic treatment, residual risk of disease progression and adverse outcomes remains substantial. Finerenone [...] Read more.

Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD) and is a risk factor for progression to end-stage kidney disease and cardiovascular morbidity and mortality. Despite pharmacologic treatment, residual risk of disease progression and adverse outcomes remains substantial. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist (MRA) approved in the United States for use in patients with CKD associated with T2D. The present review focuses on finerenone use, including its pharmacologic basis, indication and eligibility, and practical aspects of incorporation into routine clinical practice (particularly primary care). Results from the two placebo-controlled phase 3 clinical trials of finerenone (plus maximum tolerated dose of a renin-angiotensin-aldosterone system inhibitor) in patients with CKD associated with T2D showed a significantly lower risk of CKD progression and cardiovascular events with finerenone versus placebo. These effects of finerenone were applicable across the broad spectrum of patient participants, including those with baseline comorbidities such as a history of heart failure or a history of atherosclerotic cardiovascular disease. We also compare finerenone to steroidal MRAs and discuss the relevance of ongoing and recently completed clinical trials of finerenone in other patient groups, which could expand finerenone use further to a broader spectrum of patients. Full article

(This article belongs to the Section Nephrology & Urology)

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15 pages, 283 KiB

Open AccessEditor’s ChoiceReview

Biologic Therapies for Severe Asthma: Current Insights and Future Directions

by Nuno Faria, Maria Inês Costa, Ana Luísa Fernandes, António Fernandes, Beatriz Fernandes, Daniela Cunha Machado, Francisco Machado, Laura Simão, Liliana Ribeiro, Lurdes Ferreira, Rita Boaventura, Ricardo Lima and Jorge Ferreira

J. Clin. Med. 2025, 14(9), 3153; https://doi.org/10.3390/jcm14093153 - 2 May 2025

Cited by 2 | Viewed by 4376

Abstract

Severe asthma is a subset of difficult-to-treat asthma that requires the verification of inhaler technique, the correction of modifiable risk factors, as well as diagnosis and comorbidity review. When severe asthma is suspected, patients should undergo proper phenotyping (T2-high or T2-low) and be [...] Read more.

Severe asthma is a subset of difficult-to-treat asthma that requires the verification of inhaler technique, the correction of modifiable risk factors, as well as diagnosis and comorbidity review. When severe asthma is suspected, patients should undergo proper phenotyping (T2-high or T2-low) and be referred to a specialized severe asthma clinic. The current biologics for severe asthma treatment include omalizumab (anti-IgE), mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5 receptor), dupilumab (anti-IL-4/IL-13), and tezepelumab (anti-TSLP). The outcomes to evaluate are the reduction in systemic corticosteroid use, the reduction in exacerbations and healthcare use, and improvement in symptoms and lung function. Comorbidities should be carefully considered, and if possible, addressed with the same biologic. Dupilumab, mepolizumab, and omalizumab are also approved for chronic rhinosinusitis with nasal polyps (CRSwNP), the most common asthma comorbidity. There are currently several clinical trials on biologics for severe asthma. Depemokimab is an ultra-long-acting anti-IL-5 antibody with promising results in phase III trials as a twice-yearly biologic for T2-high asthma. Verekitug follows a similar dosing concept, targeting TSLP, but is still undergoing phase II trials. Itepekimab and astegolimab are two anti-IL-33 antibodies that could have a role in the future treatment of severe asthma. Tezepelumab is in a phase III clinical trial for CRSwNP. Besides new drugs, there is still a need for major research into biologics in severe asthma cases, namely with comparative studies, better biomarkers for predicting response, and the determination of optimal treatment duration. Full article

(This article belongs to the Section Respiratory Medicine)

13 pages, 2864 KiB

Open AccessEditor’s ChoiceReview

A Pragmatic Approach to Acute Cardiorenal Syndrome: Diagnostic Strategies and Targeted Therapies to Overcome Diuretic Resistance

by Patrick Tran, Laith Khweir, Michael Kuehl, Mithilesh Joshi, Krishna Appunu, Waqar Ayub and Prithwish Banerjee

J. Clin. Med. 2025, 14(9), 2996; https://doi.org/10.3390/jcm14092996 - 26 Apr 2025

Viewed by 5009

Abstract

Cardiorenal syndrome (CRS) is a challenging condition characterised by interdependent dysfunction of the heart and kidneys. Despite advancements in understanding its pathophysiology, clinical management remains complex due to overlapping mechanisms and high rates of diuretic resistance. Relevant literature was identified through a comprehensive [...] Read more.

Cardiorenal syndrome (CRS) is a challenging condition characterised by interdependent dysfunction of the heart and kidneys. Despite advancements in understanding its pathophysiology, clinical management remains complex due to overlapping mechanisms and high rates of diuretic resistance. Relevant literature was identified through a comprehensive narrative review of PubMed, Embase, and Cochrane Library databases, focusing on pivotal trials relating to CRS from 2005 to 2024. This review aims to provide a pragmatic, evidence-based approach to acute CRS management by addressing common misconceptions, outlining diagnostic strategies, and proposing a structured algorithm to manage diuretic resistance. We discuss the role of thoracic and venous excess ultrasound (VeXUS) in providing reliable measures of systemic congestion, natriuresis-guided sequential nephron blockade, and more targeted therapies, including ultrafiltration in refractory cases. In addition, we explore emerging trials that target renal hypoperfusion and venous congestion in CRS. Designed for a broad audience, including general physicians, cardiologists, and nephrologists, this review integrates clinical evidence with practical guidance to support effective and timely decision-making in the care of patients with CRS. Full article

(This article belongs to the Special Issue Latest Treatments for Cardiorenal Metabolic Disease)

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30 pages, 3837 KiB

Open AccessEditor’s ChoiceReview

Challenges and Opportunities of Direct Oral Anticoagulant (DOAC) Therapy in Complex Clinical Scenarios: A Comprehensive Review and Practical Guide

by Giuseppe Miceli, Anna Maria Ciaccio and Antonino Tuttolomondo

J. Clin. Med. 2025, 14(9), 2914; https://doi.org/10.3390/jcm14092914 - 23 Apr 2025

Viewed by 5080

Abstract

Direct oral anticoagulants (DOACs) have emerged as a preferred alternative to vitamin K antagonists (VKAs) for the prevention and treatment of thromboembolic disorders, offering improved safety, predictable pharmacokinetics, and ease of administration. Despite these advantages, their use in complex clinical scenarios presents significant [...] Read more.

Direct oral anticoagulants (DOACs) have emerged as a preferred alternative to vitamin K antagonists (VKAs) for the prevention and treatment of thromboembolic disorders, offering improved safety, predictable pharmacokinetics, and ease of administration. Despite these advantages, their use in complex clinical scenarios presents significant challenges that necessitate individualized therapeutic strategies. This comprehensive review explores the efficacy, safety, and limitations of DOAC therapy in special populations, including patients with renal or hepatic impairment, obesity, cancer-associated thrombosis, and antiphospholipid syndrome. Additionally, we examine their role in uncommon thrombotic conditions such as superficial venous thrombosis, embolic stroke of undetermined source, upper extremity vein thrombosis, inferior vena cava thrombosis, pelvic vein thrombosis, and cerebral vein thrombosis. The pharmacokinetic variability of DOACs in renal and hepatic dysfunction requires caution to balance the bleeding and thrombotic risks. In obesity, altered drug distribution and metabolism raise concerns regarding appropriate dosing and therapeutic efficacy. Cancer-associated thrombosis presents a complex interplay of prothrombotic mechanisms, necessitating careful selection of anticoagulant therapy. Furthermore, the use of DOACs in antiphospholipid syndrome remains controversial due to concerns about recurrent thrombotic events. Finally, in some unusual scenarios like inferior vena cava, pelvic vein, and cerebral vein thrombosis, the use of DOACs has scarce evidence. This review aims to guide clinicians in optimizing anticoagulation management in challenging patient populations by synthesizing current evidence and providing practical recommendations. Full article

(This article belongs to the Special Issue Thromboembolic Disease and Antithrombotic Therapy)

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15 pages, 286 KiB

Open AccessEditor’s ChoiceReview

Key Insights into Gut Alterations in Metabolic Syndrome

by Adrian Boicean, Cristian Ichim, Sabina-Maria Sasu and Samuel Bogdan Todor

J. Clin. Med. 2025, 14(8), 2678; https://doi.org/10.3390/jcm14082678 - 14 Apr 2025

Cited by 16 | Viewed by 1299

Abstract

Over time, extensive research has underscored the pivotal role of gut microbiota in the onset and progression of various diseases, with a particular focus on fecal microbiota transplantation (FMT) as a potential therapeutic approach. The practice of transferring fecal matter from a healthy [...] Read more.

Over time, extensive research has underscored the pivotal role of gut microbiota in the onset and progression of various diseases, with a particular focus on fecal microbiota transplantation (FMT) as a potential therapeutic approach. The practice of transferring fecal matter from a healthy donor to a patient provides valuable insights into how alterations in gut microbiota can impact disease development and how rectifying dysbiosis may offer therapeutic benefits. Re-establishing a balanced symbiotic relationship in the gastrointestinal tract has shown positive results in managing both intestinal and systemic conditions. Currently, one of the most pressing global health issues is metabolic syndrome—a cluster of conditions that includes insulin resistance, lipid imbalances, central obesity and hypertension. In this context, FMT has emerged as a promising strategy for addressing key components of metabolic syndrome, such as improving insulin sensitivity, body weight and lipid profiles. However, further well-structured studies are needed to refine treatment protocols and establish the long-term safety and efficacy of this intervention. Full article

(This article belongs to the Section Endocrinology & Metabolism)

12 pages, 241 KiB

Open AccessEditor’s ChoiceArticle

Sleep Quality and Mental Health Among Medical Students: A Cross-Sectional Study

by Stipe Vidović, Nada Rakić, Stela Kraštek, Ana Pešikan, Dunja Degmečić, Lada Zibar, Irena Labak, Marija Heffer and Zenon Pogorelić

J. Clin. Med. 2025, 14(7), 2274; https://doi.org/10.3390/jcm14072274 - 26 Mar 2025

Cited by 2 | Viewed by 5947

Abstract

Background: Sleep disturbances and mental health disorders represent a significant public health concern. Medical students, in particular, experience intense academic pressure, long study hours, irregular schedules, and the emotional burden of clinical training, all of which may contribute to the development of sleep [...] Read more.

Background: Sleep disturbances and mental health disorders represent a significant public health concern. Medical students, in particular, experience intense academic pressure, long study hours, irregular schedules, and the emotional burden of clinical training, all of which may contribute to the development of sleep disturbances and mental health issues. This study aims to assess sleep quality and the prevalence of symptoms of depression, anxiety, and stress among medical students, as well as their interrelationships. Methods: This multicentric cross-sectional study was conducted in January and February 2025 among medical students from two medical faculties in Croatia. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), while symptoms of depression, anxiety, and stress were evaluated using Depression, Anxiety, and Stress Scale-21 (DASS-21). Results: The study included 386 participants, of whom 96 were male and 290 were female students. It was found that 67.9% of students had poor sleep quality, while symptoms of depression, anxiety, and stress were reported by 38.8%, 45.3%, and 40.4% of participants, respectively. Female students exhibited higher PSQI scores (U = 10,205, p < 0.001), as well as higher levels of depression (U = 10,372, p < 0.001), anxiety (U = 10,328, p < 0.001), and stress scores (U = 10,560, p < 0.001). Additionally, significant moderate positive correlations were observed between the total PSQI score and depression (ρ = 0.566, p < 0.001), anxiety (ρ = 0.489, p < 0.001), and stress scores (ρ = 0.503, p < 0.001). Moreover, an increase in depression (β = 0.178, p < 0.001) and anxiety scores (β = 0.141, p < 0.001) contributed to a higher total PSQI score, indicating poorer sleep quality. Conclusions: A high prevalence of poor sleep quality and symptoms of depression, anxiety, and stress was observed among medical students, with female students exhibiting higher levels of these variables. Furthermore, poorer sleep quality was associated with higher levels of depression, anxiety, and stress. Full article

(This article belongs to the Section Mental Health)

19 pages, 2007 KiB

Open AccessEditor’s ChoiceReview

MicroRNAs in the Diagnosis of Digestive Diseases: A Comprehensive Review

by Mirela Livia Popa, Cristian Ichim, Paula Anderco, Samuel Bogdan Todor and Diana Pop-Lodromanean

J. Clin. Med. 2025, 14(6), 2054; https://doi.org/10.3390/jcm14062054 - 18 Mar 2025

Cited by 10 | Viewed by 1255

Abstract

MicroRNAs (miRNAs) have emerged as crucial regulators in digestive pathologies, including inflammatory bowel disease (miR-31, miR-155, and miR-21), colorectal cancer (miR-21, miR-598, and miR-494), and non-alcoholic fatty liver disease (miR-21, miR-192, and miR-122). Their capacity to modulate gene expression at the post-transcriptional level [...] Read more.

MicroRNAs (miRNAs) have emerged as crucial regulators in digestive pathologies, including inflammatory bowel disease (miR-31, miR-155, and miR-21), colorectal cancer (miR-21, miR-598, and miR-494), and non-alcoholic fatty liver disease (miR-21, miR-192, and miR-122). Their capacity to modulate gene expression at the post-transcriptional level makes them highly promising candidates for biomarkers and therapeutic interventions. However, despite considerable progress, their clinical application remains challenging. Research has shown that miRNA expression is highly dynamic, varying across patients, disease stages, and different intestinal regions. Their dual function as both oncogenes and tumor suppressors further complicates their therapeutic use, as targeting miRNAs may yield unpredictable effects. Additionally, while miRNA-based therapies hold great potential, significant hurdles persist, including off-target effects, immune activation, and inefficiencies in delivery methods. The intricate interplay between miRNAs and gut microbiota adds another layer of complexity, influencing disease mechanisms and treatment responses. This review examined the role of miRNAs in digestive pathologies, emphasizing their diagnostic and therapeutic potential. While they offer new avenues for disease management, unresolved challenges underscore the need for further research to refine their clinical application. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

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34 pages, 475 KiB

Open AccessEditor’s ChoiceReview

Heart Failure in Older Patients: An Update

by Massimo Montalto, Federica D’Ignazio, Sara Camilli, Silvino Di Francesco, Marco Fedele, Francesco Landi and Antonella Gallo

J. Clin. Med. 2025, 14(6), 1982; https://doi.org/10.3390/jcm14061982 - 14 Mar 2025

Cited by 1 | Viewed by 6385

Abstract

Heart failure (HF) is a clinical syndrome with high incidence and prevalence and high morbidity and death rate, even in the short term, representing a serious public health issue, mainly in older people. It is a growing cause for hospital admission in this [...] Read more.

Heart failure (HF) is a clinical syndrome with high incidence and prevalence and high morbidity and death rate, even in the short term, representing a serious public health issue, mainly in older people. It is a growing cause for hospital admission in this age group, being frequently associated with several comorbidities, further aggravating the disease’s course. Moreover, older HF patients are usually affected by clinical conditions, like frailty, malnutrition, and cachexia, which significantly impact the overall management of HF and need to be properly identified and treated. Diagnosing and managing HF in older patients may be very complicated and challenging. Although specific data on treatment of both acute and chronic HF in older subjects are limited and mainly extrapolated from large-scale clinical trials, the standard pharmacological management may be considered well-tolerated and generally safe. In any case, a personalized and tailored approach is mandatory and is based on severity of comorbidities, overall status, and prognosis, above all in frailer and more comorbid subjects, due to the higher rate of drug interactions, side effects, and therapy discontinuation in this population. In this scenario, palliative care has become a fundamental part of HF management in the elderly in order to improve their care and the quality of life. Moreover, an increasing number of promising pharmacological options deserve further investigation in order to support clinicians in optimizing management of comorbid and frailer patients. In this work, we provide detailed and updated insight into clinical, therapeutic, and prognostic features of both acute and chronic HF in the older population. Full article

(This article belongs to the Special Issue Acute and Chronic Heart Failure: Clinical Updates and Perspectives)

38 pages, 474 KiB

Open AccessEditor’s ChoiceReview

Bone Regeneration: A Review of Current Treatment Strategies

by Raffaella De Pace, Silvia Molinari, Elisa Mazzoni and Giuseppe Perale

J. Clin. Med. 2025, 14(6), 1838; https://doi.org/10.3390/jcm14061838 - 8 Mar 2025

Cited by 12 | Viewed by 7737

Abstract

Bone regeneration has emerged as a critical research and clinical advancement field, fueled by the growing demand for effective treatments in orthopedics and oncology. Over the past two decades, significant progress in biomaterials and surgical techniques has led to the development of novel [...] Read more.

Bone regeneration has emerged as a critical research and clinical advancement field, fueled by the growing demand for effective treatments in orthopedics and oncology. Over the past two decades, significant progress in biomaterials and surgical techniques has led to the development of novel solutions for treating bone defects, surpassing the use of traditional autologous grafts. This review aims to assess the latest approaches in bone regeneration, including autologous, allogenic, and xenogenic grafts, naturally derived biomaterials, and innovative synthetic substitutes such as bioceramics, bioactive glasses, metals, polymers, composite materials, and other specialized applications. A comprehensive literature search was conducted on PubMed, focusing on studies published between 2019 and 2024, including meta-analyses, reviews, and systematic reviews. The review evaluated a range of bone regeneration strategies, examining the clinical outcomes, materials used, surgical techniques, and the effectiveness of various approaches in treating bone defects. The search identified numerous studies, with the inclusion criteria focused on those exploring innovative bone regeneration strategies. These studies provided valuable insights into the clinical and biological outcomes of different biomaterials and graft types. Results indicated that while advancements in synthetic and naturally derived biomaterials show promising potential, challenges remain in optimizing therapeutic strategies across diverse patient populations and clinical settings. The findings emphasize the need for an integrated approach that combines scientific research, clinical practice, and technological innovation to improve bone regeneration therapies. Further research is required to establish standardized protocols and determine the optimal application of various materials and techniques to enhance patient outcomes and the quality of care. Full article

(This article belongs to the Section Orthopedics)

16 pages, 1698 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Paradigm Shift in Inflammatory Bowel Disease Management: Precision Medicine, Artificial Intelligence, and Emerging Therapies

by Antonio M. Caballero Mateos, Guillermo A. Cañadas de la Fuente and Beatriz Gros

J. Clin. Med. 2025, 14(5), 1536; https://doi.org/10.3390/jcm14051536 - 25 Feb 2025

Cited by 2 | Viewed by 5872

Abstract

Inflammatory bowel disease (IBD) management stands at the cusp of a transformative era, with recent breakthroughs heralding a paradigm shift in treatment strategies. Traditionally, IBD therapeutics revolved around immunosuppressants, but the landscape has evolved significantly. Recent approvals of etrasimod, upadacitinib, mirikizumab, and risankizumab [...] Read more.

Inflammatory bowel disease (IBD) management stands at the cusp of a transformative era, with recent breakthroughs heralding a paradigm shift in treatment strategies. Traditionally, IBD therapeutics revolved around immunosuppressants, but the landscape has evolved significantly. Recent approvals of etrasimod, upadacitinib, mirikizumab, and risankizumab have introduced novel mechanisms of action, offering renewed hope for IBD patients. These medications represent a departure from the status quo, breaking years of therapeutic stagnation. Precision medicine, involving Artificial Intelligence, is a pivotal aspect of this evolution, tailoring treatments based on genetic profiles, disease characteristics, and individual responses. This approach optimizes treatment efficacy, and paves the way for personalized care. Yet, the rising cost of IBD therapies, notably biologics, poses challenges, impacting healthcare budgets and patient access. Ongoing research strives to assess cost-effectiveness, guiding policy decisions to ensure equitable access to advanced treatments. Looking ahead, the future of IBD management holds great promise. Emerging therapies, precision medicine, and ongoing research into novel targets promise to reshape the IBD treatment landscape. As these advances continue to unfold, IBD patients can anticipate a brighter future, one marked by more effective, personalized, and accessible treatments. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease: Clinical Advances and Therapeutic Prospects)

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15 pages, 664 KiB

Open AccessEditor’s ChoiceReview

Review of Recent Treatment Strategies for Lumbar Disc Herniation (LDH) Focusing on Nonsurgical and Regenerative Therapies

by Jae Sun Lee, Soo-Bin Lee, Kyung-Yil Kang, Seong Ho Oh and Dong-Sik Chae

J. Clin. Med. 2025, 14(4), 1196; https://doi.org/10.3390/jcm14041196 - 12 Feb 2025

Cited by 4 | Viewed by 10975

Abstract

Conservative treatment is primarily performed for the treatment of patients with lumbar disc herniation (LDH), but if it does not respond, surgical treatment can be performed. Surgical intervention has a positive effect on the rapid improvement of LDH symptoms. However, the effectiveness of [...] Read more.

Conservative treatment is primarily performed for the treatment of patients with lumbar disc herniation (LDH), but if it does not respond, surgical treatment can be performed. Surgical intervention has a positive effect on the rapid improvement of LDH symptoms. However, the effectiveness of surgical versus conservative treatment for LDH is controversial, especially regarding long-term effects. Recently, a treatment using platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), low-intensity pulsed ultrasound (LIPUS), etc., has been actively conducted as a treatment to avoid side effects of surgery and promote tissue regeneration. In this paper, the literature evaluating the effectiveness of non-surgical treatment options is reviewed with an emphasis on the effectiveness of clinical application. Several clinical studies have shown that PRP, biomaterials, BMAC, and LIPUS treatment promote tissue regeneration and alleviate symptoms. Although PRP-applied studies have suggested disc height changes, cell therapy and LIPUS treatment have many shortcomings in clinical aspects of tissue regeneration. Therefore, it is necessary to establish a unified, safe protocol and standardize the method of presenting results to confirm the clinical effect of the treatment for impaired intervertebral regeneration in patients with intervertebral disc degeneration (IDD), including LDH. Full article

(This article belongs to the Section Orthopedics)

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13 pages, 894 KiB

Open AccessEditor’s ChoiceSystematic Review

Cine-MRI for Quantifying Uterine Peristalsis: A Systematic Review and Meta-Analysis

by Angela Vidal, Cristina Bora, Jeannette von Holzen, Marietta Gulz, Verena C. Obmann, Janna Pape, Tanya Karrer, Gürkan Yilmaz and Michael von Wolff

J. Clin. Med. 2025, 14(3), 1021; https://doi.org/10.3390/jcm14031021 - 6 Feb 2025

Cited by 5 | Viewed by 1352

Abstract

Background: Uterine contractility, also known as uterine peristalsis (UP), is a critical determinant of fertility, affecting sperm transport and embryo implantation. Increased uterine peristaltic activity has been associated with reduced pregnancy rates. However, data are heterogeneous and uterine contractility has not been widely [...] Read more.

Background: Uterine contractility, also known as uterine peristalsis (UP), is a critical determinant of fertility, affecting sperm transport and embryo implantation. Increased uterine peristaltic activity has been associated with reduced pregnancy rates. However, data are heterogeneous and uterine contractility has not been widely translated into clinical practice. Cine-MRI, although limited by cost and heterogeneity in data reporting, has emerged as a promising tool to assess uterine dynamics and increase our knowledge of UP in physiological and pathological conditions. Objective: This systematic review and meta-analysis aimed to describe patterns of UP in physiological and pathological uterine conditions, including endometriosis and fibroids, using cine-MRI. Methods: A systematic literature search of the Medline, Embase, Cochrane and CENTRAL databases and Google Scholar was conducted up to May 2024, including studies evaluating UP by cine-MRI. Clinical studies evaluating uterine contractility were included, excluding those affected by therapeutic interventions or unrelated pathologies. This meta-analysis pooled data from studies comparing uterine contractility in patients with endometriosis. Results: In the 13 included studies (365 women), uterine contractility varied significantly according to menstrual cycle phases and pathological conditions. This meta-analysis showed that women with endometriosis had higher uterine contractility in the luteal phase (0.74; 95% CI: 0.27–1.21) but not in the periovulatory phase (SMD 0.8; 95% CI: −3.78–5.37). Conclusions: Cine-MRI is a promising diagnostic tool for the analysis of UP. Endometriosis is associated with impaired UP, which may be a cause of the decreased implantation rate and infertility in endometriosis. However, further research is needed to consolidate the effect of UP on implantation and fertility and to develop standardised and cost-effective tools to assess uterine contractility and tailor infertility treatment. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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37 pages, 2637 KiB

Open AccessEditor’s ChoiceReview

Septic Cardiomyopathy: Difficult Definition, Challenging Diagnosis, Unclear Treatment

by George E. Zakynthinos, Grigorios Giamouzis, Andrew Xanthopoulos, Evangelos Oikonomou, Konstantinos Kalogeras, Nikitas Karavidas, Ilias E. Dimeas, Ioannis Gialamas, Maria Ioanna Gounaridi, Gerasimos Siasos, Manolis Vavuranakis, Epaminondas Zakynthinos and Vasiliki Tsolaki

J. Clin. Med. 2025, 14(3), 986; https://doi.org/10.3390/jcm14030986 - 4 Feb 2025

Cited by 4 | Viewed by 7578

Abstract

Sepsis is a systemic inflammatory response syndrome of suspected or confirmed infectious origin, which frequently culminates in multiorgan failure, including cardiac involvement. Septic cardiomyopathy (SCM) remains a poorly defined clinical entity, lacking a formal or consensus definition and representing a significant knowledge gap [...] Read more.

Sepsis is a systemic inflammatory response syndrome of suspected or confirmed infectious origin, which frequently culminates in multiorgan failure, including cardiac involvement. Septic cardiomyopathy (SCM) remains a poorly defined clinical entity, lacking a formal or consensus definition and representing a significant knowledge gap in critical care medicine. It is an often-underdiagnosed complication of sepsis. The only widely accepted aspect of its definition is that SCM is a transient myocardial dysfunction occurring in patients with sepsis, which cannot be attributed to ischemia or pre-existing cardiac disease. The pathogenesis of SCM appears to be multifactorial, involving inflammatory cytokines, overproduction of nitric oxide, mitochondrial dysfunction, calcium homeostasis dysregulation, autonomic imbalance, and myocardial edema. Diagnosis primarily relies on echocardiography, with advanced tools such as tissue Doppler imaging (TDI) and global longitudinal strain (GLS) providing greater sensitivity for detecting subclinical dysfunction and guiding therapeutic decisions. Traditional echocardiographic findings, such as left ventricular ejection fraction measured by 2D echocardiography, often reflect systemic vasoplegia rather than intrinsic myocardial dysfunction, complicating accurate diagnosis. Right ventricular (RV) dysfunction, identified as a critical component of SCM in many studies, has multifactorial pathophysiology. Factors including septic cardiomyopathy itself, mechanical ventilation, hypoxemia, and hypercapnia—particularly in cases complicated by acute respiratory distress syndrome (ARDS)—increase RV afterload and exacerbate RV dysfunction. The prognostic value of cardiac biomarkers, such as troponins and natriuretic peptides, remains uncertain, as these markers primarily reflect illness severity rather than being specific to SCM. Treatment focuses on the early recognition of sepsis, hemodynamic optimization, and etiological interventions, as no targeted therapies currently exist. Emerging therapies, such as levosimendan and VA-ECMO, show potential in severe SCM cases, though further validation is needed. The lack of standardized diagnostic criteria, combined with the heterogeneity of sepsis presentations, poses significant challenges to the effective management of SCM. Future research should focus on developing cluster-based classification systems for septic shock patients by integrating biomarkers, echocardiographic findings, and clinical parameters. These advancements could clarify the underlying pathophysiology and enable tailored therapeutic strategies to improve outcomes for SCM patients. Full article

(This article belongs to the Section Cardiology)

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18 pages, 690 KiB

Open AccessEditor’s ChoiceReview

Advancements in Artificial Intelligence for Kidney Transplantology: A Comprehensive Review of Current Applications and Predictive Models

by Jakub Mizera, Maciej Pondel, Marta Kepinska, Patryk Jerzak and Mirosław Banasik

J. Clin. Med. 2025, 14(3), 975; https://doi.org/10.3390/jcm14030975 - 3 Feb 2025

Cited by 5 | Viewed by 1675

Abstract

Background: Artificial intelligence is rapidly advancing within the domains of medicine and transplantology. In this comprehensive review, we provide an in-depth exploration of current AI methodologies, with a particular emphasis on machine learning and deep learning techniques, and their diverse subtypes. These technologies [...] Read more.

Background: Artificial intelligence is rapidly advancing within the domains of medicine and transplantology. In this comprehensive review, we provide an in-depth exploration of current AI methodologies, with a particular emphasis on machine learning and deep learning techniques, and their diverse subtypes. These technologies are revolutionizing how data are processed, analyzed, and applied in clinical decision making. Methods: A meticulous literature review was conducted with a focus on the application of artificial intelligence in kidney transplantation. Four research questions were formulated to establish the aim of the review. Results: We thoroughly examined the general applications of AI in the medical field, such as feature selection, dimensionality reduction, and clustering, which serve as foundational tools for complex data analysis. This includes the development of predictive models for transplant rejection, the optimization of personalized immunosuppressive therapies, the algorithmic matching of donors and recipients based on multidimensional criteria, and the sophisticated analysis of histopathological images to improve the diagnostic accuracy. Moreover, we present a detailed comparison of existing AI-based algorithms designed to predict kidney graft survival in transplant recipients. In this context, we focus on the variables incorporated into these predictive models, providing a critical analysis of their relative importance and contribution to model performance. Conclusions: This review highlights the significant advancements made possible through AI and underscores its potential to enhance both clinical outcomes and the precision of medical interventions in the field of transplantology. Full article

(This article belongs to the Special Issue Applications of Artificial Intelligence and Digital Therapeutics in Clinical Medicine)

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13 pages, 428 KiB

Open AccessEditor’s ChoiceArticle

Pancreatitis Risk Associated with GLP-1 Receptor Agonists, Considered as a Single Class, in a Comorbidity-Free Subgroup of Type 2 Diabetes Patients in the United States: A Propensity Score-Matched Analysis

by Mark Ayoub, Harleen Chela, Nisar Amin, Roberta Hunter, Javaria Anwar, Veysel Tahan and Ebubekir Daglilar

J. Clin. Med. 2025, 14(3), 944; https://doi.org/10.3390/jcm14030944 - 1 Feb 2025

Cited by 7 | Viewed by 5191

Abstract

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly prescribed for the management of type 2 diabetes mellitus (T2DM). However, the potential connection between GLP-1 RAs and the risk of pancreatitis presents a complex and nuanced issue. Although these drugs are effective in [...] Read more.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly prescribed for the management of type 2 diabetes mellitus (T2DM). However, the potential connection between GLP-1 RAs and the risk of pancreatitis presents a complex and nuanced issue. Although these drugs are effective in improving blood sugar control and cardiovascular health, their association with pancreatitis remains an area of concern. Our study aims to evaluate the association between the use of GLP-1 RAs, considered as a single class, and the risk of pancreatitis in a comorbidity-free subgroup of patients with type 2 diabetes mellitus (T2DM) in the United States. Methods: Data were retrieved from the TriNetX research database using the US Collaborative Network, which included information from 61 healthcare organizations within the U.S. Patients diagnosed with T2DM were categorized into two cohorts: one consisting of the patients prescribed with GLP-1 RAs and the other comprising patients who did not receive GLP-1 RAs. Of this class of medications, the agents analyzed were dulaglutide, lixisenatide, exenatide, liraglutide, and semaglutide. Using a 1:1 propensity score matching (PSM) model, we matched patients of both cohorts based on baseline demographics, comorbidities (hypertensive disorders, ischemic heart disease, gallstones, annular pancreas, alcohol use disorders, hypertriglyceridemia, hypercalcemia, cystic fibrosis, and cannabis use), medications known to cause drug-related pancreatitis, and laboratory values. Results: Of 969,240 patients with T2DM, 9.7% (93,608) were on GLP-1 RA, and 90.3% (875,632) were not. After PSM, the sample included 81,872 patients in each cohort. The risk of pancreatitis between the two groups was not statistically different between the two cohorts at 6 months at (0.1% vs. 0.1%, p = 0.04), and remained without significant increase with time; at 1 year (0.1% vs. 0.2%, p = 0.02), 3 years (0.2% vs. 0.3%, p = 0.001), and 5 years (0.3% vs. 0.4%, p < 0.001). The lifetime risk of developing pancreatitis in patients on GLP-1 RA was lower (0.3% vs. 0.4%, p < 0.001). Conclusions: In our comorbidity-free U.S.-based population with T2DM, the use of GLP-1 RAs did not increase their risk of pancreatitis. Their use was associated with a lower lifetime risk of pancreatitis. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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14 pages, 888 KiB

Open AccessEditor’s ChoiceReview

Machine Learning in Pediatric Healthcare: Current Trends, Challenges, and Future Directions

by Hammad A. Ganatra

J. Clin. Med. 2025, 14(3), 807; https://doi.org/10.3390/jcm14030807 - 26 Jan 2025

Cited by 9 | Viewed by 2671

Abstract

Background/Objectives: Artificial intelligence (AI) and machine learning (ML) are transforming healthcare by enabling predictive, diagnostic, and therapeutic advancements. Pediatric healthcare presents unique challenges, including limited data availability, developmental variability, and ethical considerations. This narrative review explores the current trends, applications, challenges, and [...] Read more.

Background/Objectives: Artificial intelligence (AI) and machine learning (ML) are transforming healthcare by enabling predictive, diagnostic, and therapeutic advancements. Pediatric healthcare presents unique challenges, including limited data availability, developmental variability, and ethical considerations. This narrative review explores the current trends, applications, challenges, and future directions of ML in pediatric healthcare. Methods: A systematic search of the PubMed database was conducted using the query: (“artificial intelligence” OR “machine learning”) AND (“pediatric” OR “paediatric”). Studies were reviewed to identify key themes, methodologies, applications, and challenges. Gaps in the research and ethical considerations were also analyzed to propose future research directions. Results: ML has demonstrated promise in diagnostic support, prognostic modeling, and therapeutic planning for pediatric patients. Applications include the early detection of conditions like sepsis, improved diagnostic imaging, and personalized treatment strategies for chronic conditions such as epilepsy and Crohn’s disease. However, challenges such as data limitations, ethical concerns, and lack of model generalizability remain significant barriers. Emerging techniques, including federated learning and explainable AI (XAI), offer potential solutions. Despite these advancements, research gaps persist in data diversity, model interpretability, and ethical frameworks. Conclusions: ML offers transformative potential in pediatric healthcare by addressing diagnostic, prognostic, and therapeutic challenges. While advancements highlight its promise, overcoming barriers such as data limitations, ethical concerns, and model trustworthiness is essential for its broader adoption. Future efforts should focus on enhancing data diversity, developing standardized ethical guidelines, and improving model transparency to ensure equitable and effective implementation in pediatric care. Full article

(This article belongs to the Section Clinical Pediatrics)

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24 pages, 1210 KiB

Open AccessEditor’s ChoiceReview

Future Directions in Diabetic Retinopathy Treatment: Stem Cell Therapy, Nanotechnology, and PPARα Modulation

by Maria Kąpa, Iga Koryciarz, Natalia Kustosik, Piotr Jurowski and Zofia Pniakowska

J. Clin. Med. 2025, 14(3), 683; https://doi.org/10.3390/jcm14030683 - 21 Jan 2025

Cited by 6 | Viewed by 3692

Abstract

This narrative review focuses on innovative treatment approaches to diabetic retinopathy to meet the urgent demand for advancements in managing both the early and late stages of the disease. Recent studies highlight the potential of adipose stem cells and their secreted factors in [...] Read more.

This narrative review focuses on innovative treatment approaches to diabetic retinopathy to meet the urgent demand for advancements in managing both the early and late stages of the disease. Recent studies highlight the potential of adipose stem cells and their secreted factors in mitigating the retinal complications of diabetes, with promising results in improving visual acuity and reducing inflammation and angiogenesis in diabetic retinopathy. However, caution is warranted regarding the safety and long-term therapeutic effects of adipose stem cells transplantation. Bone marrow mesenchymal stem cells can also mitigate retinal damage in diabetic retinopathy. Studies demonstrate that bone marrow mesenchymal stem cells-derived exosomes can suppress the Wnt/β-catenin pathway, reducing oxidative stress, inflammation, and angiogenesis in the diabetic retina, offering promise for future diabetic retinopathy treatments. Nanotechnology has the ability to precisely target the retina and minimize systemic side effects. Nanoparticles and nanocarriers offer improved bioavailability, sustained release of therapeutics, and potential for synergistic effects. They can be a new way of effective treatment and prevention of diabetic retinopathy. Activation and modulation of PPARα as a means for diabetic retinopathy treatment has been widely investigated in recent years and demonstrated promising effects in clinical trials. PPARα activation turned out to be a promising therapeutic method for treating dyslipidemia, inflammation, and insulin sensitivity. The combination of PPARα modulators with small molecules offers an interesting perspective for retinal diseases’ therapy. Full article

(This article belongs to the Special Issue Diabetic Retinopathy: Current Concepts and Future Directions)

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50 pages, 3786 KiB

Open AccessEditor’s ChoiceReview

The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications

by Sehwan Kim, Un Ju Jung and Sang Ryong Kim

J. Clin. Med. 2025, 14(2), 386; https://doi.org/10.3390/jcm14020386 - 9 Jan 2025

Cited by 10 | Viewed by 4856

Abstract

The blood–brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from the bloodstream into the central nervous system (CNS). Neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, as well as ischemic stroke, compromise [...] Read more.

The blood–brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from the bloodstream into the central nervous system (CNS). Neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, as well as ischemic stroke, compromise the integrity of the BBB. This leads to increased permeability and the infiltration of harmful substances, thereby accelerating neurodegeneration. In this review, we explore the mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, and the loss of tight junction integrity, in patients with neurodegenerative diseases. We discuss how BBB breakdown contributes to neuroinflammation, neurotoxicity, and the abnormal accumulation of pathological proteins, all of which exacerbate neuronal damage and facilitate disease progression. Furthermore, we discuss potential therapeutic strategies aimed at preserving or restoring BBB function, such as anti-inflammatory treatments, antioxidant therapies, and approaches to enhance tight junction integrity. Given the central role of the BBB in neurodegeneration, maintaining its integrity represents a promising therapeutic approach to slow or prevent the progression of neurodegenerative diseases. Full article

(This article belongs to the Section Clinical Neurology)

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17 pages, 562 KiB

Open AccessEditor’s ChoiceReview

Managing Retinitis Pigmentosa: A Literature Review of Current Non-Surgical Approaches

by Leonardo Colombo, Jacopo Baldesi, Salvatore Martella, Chiara Quisisana, Aleksei Antico, Luca Mapelli, Stefania Montagner, Alberto Primon and Luca Rossetti

J. Clin. Med. 2025, 14(2), 330; https://doi.org/10.3390/jcm14020330 - 8 Jan 2025

Cited by 4 | Viewed by 4859

Abstract

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases characterized by the progressive loss of photoreceptor function, visual impairment, and, ultimately, blindness. While gene therapy has emerged as a promising therapy, it is currently available only for the RPE65 gene mutation, [...] Read more.

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases characterized by the progressive loss of photoreceptor function, visual impairment, and, ultimately, blindness. While gene therapy has emerged as a promising therapy, it is currently available only for the RPE65 gene mutation, leaving many patients without targeted genetic treatments. Non-surgical interventions may help in managing the progression of RP and improving patients’ quality of life. Visual training and rehabilitation, maximizing residual vision, have shown potential in improving mobility and patients’ ability to perform daily activities. Visual aids enhance visual function. Moreover, photo-protection demonstrated effectiveness in mitigating light-induced damage and improving visual comfort. Alternative therapies (i.e., electrostimulation, acupuncture, and ozone therapy) are being explored to preserve retinal function and reduce disease progression. Pharmacological interventions supported by nutritional and psychological counseling play a role in slowing retinal degeneration while managing the emotional burden of progressive vision loss. Although for these interventions, further validation is required, their potential benefits make them valuable additions to care for RP patients. The integration of these interventions into a multidisciplinary care approach—including ophthalmologists, orthoptist, dietitians, and psychologists—is essential for providing comprehensive, personalized care to RP patients while awaiting more widespread gene therapy solutions. Full article

(This article belongs to the Section Ophthalmology)

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16 pages, 3163 KiB

Open AccessEditor’s ChoiceReview

Node Reporting and Data System 1.0 (Node-RADS) for the Assessment of Oncological Patients’ Lymph Nodes in Clinical Imaging

by Marco Parillo and Carlo Cosimo Quattrocchi

J. Clin. Med. 2025, 14(1), 263; https://doi.org/10.3390/jcm14010263 - 5 Jan 2025

Cited by 5 | Viewed by 2055

Abstract

The assessment of lymph node (LN) involvement with clinical imaging is a key factor in cancer staging. Node Reporting and Data System 1.0 (Node-RADS) was introduced in 2021 as a new system specifically tailored for classifying and reporting LNs on computed tomography (CT) [...] Read more.

The assessment of lymph node (LN) involvement with clinical imaging is a key factor in cancer staging. Node Reporting and Data System 1.0 (Node-RADS) was introduced in 2021 as a new system specifically tailored for classifying and reporting LNs on computed tomography (CT) and magnetic resonance imaging scans. The aim of this review is to compile the scientific evidence that has emerged since the introduction of Node-RADS, with a specific focus on its diagnostic performance and reliability. Node-RADS’s performance has been evaluated in various cancer types and anatomical sites, revealing a trend where higher Node-RADS scores correspond to a greater probability of metastatic LN with better diagnostic performances compared to using short axis diameter alone. Moreover, Node-RADS exhibits encouraging diagnostic value for both Node-RADS ≥ 3 and Node-RADS ≥ 4 cutoffs in predicting metastatic LN. In terms of Node-RADS scoring reliability, preliminary studies show promising but partially conflicting results, with agreement levels, mostly between two readers, ranging from fair to almost perfect. This review highlights a wide variation in methodologies across different studies. Thus, to fully realize the potential of Node-RADS in clinical practice, future studies should comprehensively evaluate its diagnostic accuracy, category-specific malignancy rates, and inter-observer agreement. Finally, although limited, promising evidence has suggested the following: a potential prognostic role for Node-RADS; the possible value of diffusion-weighted imaging for LNs classified as Node-RADS ≥ 3; a correlation between Node-RADS and certain texture features in CT; and improved diagnostic performance when Node-RADS is integrated into radiomics or clinical models. Full article

(This article belongs to the Section Nuclear Medicine & Radiology)

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13 pages, 1335 KiB

Open AccessEditor’s ChoiceArticle

Clinical Profiles, Survival, and Lung Function Outcomes in ANCA-Associated Interstitial Lung Disease: An Observational Study

by Cristina Valero-Martínez, Claudia Valenzuela, Juan Pablo Baldivieso Achá, Elisa Martínez-Besteiro, Patricia Quiroga-Colina, Arantzazu Alfranca, Esther F. Vicente-Rabaneda, Susana Hernández Muñiz, Santos Castañeda and Rosario García-Vicuña

J. Clin. Med. 2025, 14(1), 229; https://doi.org/10.3390/jcm14010229 - 3 Jan 2025

Cited by 5 | Viewed by 1394

Abstract

Background/Objectives: Anti-neutrophil cytoplasmic antibodies (ANCAs) have been found in interstitial lung disease (ILD) in recent years, although its impact on ILD prognosis is less known. To date, ANCAs are not included in the interstitial pneumonia with autoimmune features (IPAF) definition criteria. Therefore, [...] Read more.

Background/Objectives: Anti-neutrophil cytoplasmic antibodies (ANCAs) have been found in interstitial lung disease (ILD) in recent years, although its impact on ILD prognosis is less known. To date, ANCAs are not included in the interstitial pneumonia with autoimmune features (IPAF) definition criteria. Therefore, ANCA-ILD, in the absence of known ANCA-associated vasculitis (AAV), could be underdiagnosed. Our aim was to analyze the clinical profile and prognosis of ANCA-ILD patients. Methods: Patients diagnosed with ILD and positive ANCA were enrolled in a retrospective, monocentric cohort study. Lung function outcomes and mortality were assessed according to clinical, serological, radiological, and treatment characteristics. Survival was analyzed using Kaplan–Meier curves and Cox regression models. Results: A total of 23 patients were included, mostly women, with a median time from ILD diagnosis of 36 (24–68) months and a predominant anti-MPO pattern (56.5%). Nearly half of the patients had AAV, mostly microscopic polyangiitis (MPA). The presence of AAV was significantly associated with anti-MPO antibodies and an NSIP radiographic pattern. Overall, the fibrotic pattern (either UIP or fibrotic NSIP) was the most common (73.9%), mainly UIP (51.2%). However, it appeared less frequently in the AAV-ILD group. During follow-up, lung function impairment or radiological progression was observed in 65.2% of patients. Cumulative mortality incidence was high (43.4%), largely due to ILD itself (80%). A UIP pattern was associated with a higher and earlier mortality (HR 34.4 [1.36–132]), while the use of immunosuppressants showed a trend towards lower ILD-related death. Conclusions: In our cohort, ANCA-ILD patients mostly presented with fibrotic patterns, with AAV in almost half of the cases and a high and early mortality rate, which suggests the need to assess ANCA in all ILD patients. Full article

(This article belongs to the Special Issue Systemic Vasculitis: Advancement in Pathogenesis, Clinical Features, Management and Therapeutic Strategies)

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