Journal of Clinical Medicine

13 pages, 831 KB

Open AccessArticle

Robot-Assisted Radical Prostatectomy as the Institutional Standard: Complete Transition and Contemporary Outcomes from a High-Volume European Center

by Simon Hawlina, Andraž Kondža, Kosta Cerović and Jure Bizjak

J. Clin. Med. 2026, 15(12), 4606; https://doi.org/10.3390/jcm15124606 (registering DOI) - 13 Jun 2026

Abstract

Background: Robot-assisted radical prostatectomy (RARP) is the predominant surgical approach for localized prostate cancer in high-volume centers worldwide. However, comprehensive real-world data describing complete institutional transition from open to robotic surgery remain limited. This study evaluated perioperative and early oncological outcomes of [...] Read more.

Background: Robot-assisted radical prostatectomy (RARP) is the predominant surgical approach for localized prostate cancer in high-volume centers worldwide. However, comprehensive real-world data describing complete institutional transition from open to robotic surgery remain limited. This study evaluated perioperative and early oncological outcomes of a contemporary RARP cohort and characterized the transition from open radical prostatectomy (ORP) to RARP in a European center. Methods: We analyzed 520 consecutive patients who underwent RARP between January 2023 and December 2025. Perioperative, pathological, and biochemical outcomes were assessed. Biochemical recurrence was defined as prostate-specific antigen ≥0.2 ng/mL. Institutional data from 2011 to 2025 were reviewed to evaluate procedural trends and the transition from ORP to RARP. Surgeon-specific and institutional learning curves were analyzed using operative time and linear regression models. Results: Following the introduction of robotic surgery in 2018, annual RARP volume increased from 37 procedures to 205 in 2025. Since 2023, RARP accounted for more than 99% of all radical prostatectomies. Median operative time decreased from 185 min in 2023 to 165 min in 2025, with consistent downward trends observed across all surgeons. Linear regression confirmed progressive improvement in operative efficiency, with learning rates ranging from −0.22 to −0.92 min per case. Estimated blood loss was minimal, no patients required transfusion, and major complications occurred in four patients (0.8%). Hospital stay decreased from 2 days to predominantly 1 day. During follow-up, 36 patients developed biochemical recurrence or PSA persistence. Biochemical recurrence-free survival differed significantly according to pathological stage (log-rank p < 0.001), with 24-month estimates of 93.7%, 91.5%, and 82.1% for pT2, pT3a, and pT3b disease, respectively. Conclusions: RARP provides favorable perioperative safety, minimal morbidity, and favorable early oncological outcomes in a high-volume setting. The complete institutional transition from ORP to RARP, together with demonstrated surgeon-specific and institutional learning effects, supports the feasibility and safety of implementing RARP as the institutional standard within a structured robotic program. Full article

(This article belongs to the Special Issue Clinical Advances in Risk Minimization Through Robot-Assisted Surgery)

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14 pages, 4057 KB

Open AccessArticle

Prevalence, Clinical and Functional Determinants of Chronic Hypoxemia and Respiratory Failure in Patients with Stable COPD

by Giacobbe Marco Giuseppe Ricco, Dejan Radovanovic, Matteo Pecchiari, Marina Saad, Juan Camilo Signorello, Francesca Mandurino Mirizzi, Michele Mondoni, Massimo Guerriero and Pierachille Santus

J. Clin. Med. 2026, 15(12), 4605; https://doi.org/10.3390/jcm15124605 (registering DOI) - 13 Jun 2026

Abstract

Background and objective: Hypoxemia and respiratory failure (RF) in chronic obstructive pulmonary disease (COPD) are associated with exacerbations, comorbidities and increased mortality. However, the prevalence of hypoxemia and RF in stable COPD is unknown. We aimed at investigating the prevalence and determining [...] Read more.

Background and objective: Hypoxemia and respiratory failure (RF) in chronic obstructive pulmonary disease (COPD) are associated with exacerbations, comorbidities and increased mortality. However, the prevalence of hypoxemia and RF in stable COPD is unknown. We aimed at investigating the prevalence and determining predictive factors for chronic gas exchange abnormalities in COPD patients. Methods: A retrospective cohort study that enrolled clinically stable COPD patients referring to a pulmonary outpatient clinic. Anthropometrics, clinical characteristics, blood gas analysis and lung function were analyzed. Patients were grouped according to hypoxemia (PaO₂ <80 and ≥60 mmHg), type 1 (PaO₂ < 60 mmHg) or type II (PaO₂ < 60 and PaCO₂ > 45 mmHg) RF. A sensitivity analysis adopting an age-adjusted definition of hypoxemia was performed. Predictive factors for hypoxemia or RF were assessed with multifactorial analysis. Results: We analyzed data from 515 patients. Fixed-ratio hypoxemia, RF type 1 and type 2 were observed in 352 (68.3%), 27 (5.2%) and 43 (8.3%) patients, respectively. Risk of hypoxemia was associated with preserved alveolar volume, residual volume/total lung capacity, and lung diffusion capacity. Heart failure, ischemic heart disease, atrial fibrillation, and metabolic syndrome were predictive factors for RF. Patients with age-adjusted hypoxemia (n = 321 patients, 62.3%) showed no difference in terms of anthropometrics, lung function, and clinical characteristics as compared with fixed-threshold hypoxemia. Conclusions: Hypoxemia is frequent in stable COPD. Lung function parameters and comorbidities can support the identification of patients at risk of RF. Blood gas analysis should be always performed in patients with COPD to allow for personalized therapy and management. Full article

(This article belongs to the Section Respiratory Medicine)

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Graphical abstract

13 pages, 770 KB

Open AccessArticle

Sex Differences in Clinical Profile, Revascularization and In-Hospital Outcomes in Patients with ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

by Corina Cinezan, Camelia Bianca Rus and Timea Claudia Ghitea

J. Clin. Med. 2026, 15(12), 4604; https://doi.org/10.3390/jcm15124604 (registering DOI) - 13 Jun 2026

Abstract

Background/Objectives: Sex differences in ST-elevation myocardial infarction (STEMI) outcomes persist despite advances in primary percutaneous coronary intervention (PCI), but whether female sex independently influences early mortality remains unclear. study aimed to assess sex-based differences in clinical characteristics, management, in-hospital outcomes and to [...] Read more.

Background/Objectives: Sex differences in ST-elevation myocardial infarction (STEMI) outcomes persist despite advances in primary percutaneous coronary intervention (PCI), but whether female sex independently influences early mortality remains unclear. study aimed to assess sex-based differences in clinical characteristics, management, in-hospital outcomes and to determine whether female sex independently predicts in-hospital mortality. Methods: This retrospective observational study included 512 consecutive patients with STEMI presenting within 6 h of symptom onset and treated with primary PCI. Clinical, laboratory, echocardiographic and angiographic data were analyzed. The primary endpoint was in-hospital mortality. Multivariable logistic regression identified independent predictors of mortality. Results: Women comprised 32.0% of the cohort and were older than men (median 69 vs. 59 years, p < 0.001), with a higher prevalence of diabetes and hypertension, but lower rates of smoking (all p < 0.001). Women had lower hemoglobin levels and a higher prevalence of moderate-to-severe mitral regurgitation (17.1% vs. 8.0%, p = 0.004). Procedural characteristics, including door-to-balloon time and complete revascularization, were similar between sexes. Crude in-hospital mortality was higher in women (13.4% vs. 7.5%, p = 0.047); however, female sex was not independently associated with mortality after adjustment (adjusted OR 1.07, 95% CI 0.48–2.41; p = 0.864). Lower LVEF and reduced GFR were the strongest independent predictors of death. Conclusions: Higher mortality in women is primarily driven by a more adverse clinical profile rather than sex itself, emphasizing the importance of early risk stratification and management. Full article

(This article belongs to the Special Issue Acute Coronary Syndrome(ACS): From Emergency Intervention to Long-Term Prevention)

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21 pages, 3402 KB

Open AccessReview

Insomnia in Breast Cancer: A Neglected Symptom Cluster

by Giuseppe Marano, Ida Paris, Gianandrea Traversi, Osvaldo Mazza, Antonella Migliore, Valentina Ricozzi, Silvia Rotondaro, Francesco Pavese, Tatiana D’Angelo, Paola Fuso, Alessandra Fabi, Gianluca Franceschini and Marianna Mazza

J. Clin. Med. 2026, 15(12), 4603; https://doi.org/10.3390/jcm15124603 (registering DOI) - 13 Jun 2026

Abstract

Background/Objectives: Insomnia is one of the most prevalent and persistent symptoms among patients with breast cancer, yet it remains under-recognized and undertreated in routine clinical practice. Beyond its impact on sleep quality, insomnia is increasingly understood as a multidimensional condition involving neurobiological, [...] Read more.

Background/Objectives: Insomnia is one of the most prevalent and persistent symptoms among patients with breast cancer, yet it remains under-recognized and undertreated in routine clinical practice. Beyond its impact on sleep quality, insomnia is increasingly understood as a multidimensional condition involving neurobiological, psychological, and behavioral mechanisms, closely intertwined with cancer-related stress and psychiatric comorbidities. This narrative review aims to provide a comprehensive and integrative overview of insomnia in breast cancer, focusing on its epidemiology, pathophysiological underpinnings, neuropsychiatric correlates, and clinical implications, while highlighting gaps in current research and management. Methods: A narrative review of the literature was conducted, including studies published in major medical databases (PubMed, Scopus, and Web of Science) up to 2025. Relevant articles addressing insomnia, sleep disturbances, psychiatric symptoms, and neurobiological mechanisms in breast cancer populations were selected and synthesized. Results: Insomnia affects a substantial proportion of breast cancer patients across the disease trajectory, from diagnosis to survivorship. Its etiology is multifactorial, involving dysregulation of the hypothalamic–pituitary–adrenal axis, inflammatory processes, and circadian rhythm, as well as treatment-related factors such as chemotherapy, endocrine therapy, and menopausal symptoms. Insomnia frequently co-occurs with depression, anxiety, fatigue, and pain, forming symptom clusters that significantly impair quality of life and may influence clinical outcomes. Emerging evidence supports a bidirectional relationship between insomnia and psychiatric vulnerability, suggesting a shared neurobiological substrate within the brain–body stress axis. Conclusions: Insomnia in breast cancer should be conceptualized as a neuropsychiatric condition embedded within a broader stress-related symptom network rather than as an isolated sleep disturbance. Improved screening, interdisciplinary management, and the integration of evidence-based interventions such as cognitive behavioral therapy for insomnia are essential. Research should focus on personalized and mechanistically informed approaches to better address this highly prevalent yet insufficiently managed condition. Full article

(This article belongs to the Special Issue Breast Cancer: Advances in Clinical and Personalized Practices)

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13 pages, 233 KB

Open AccessArticle

Functional Status of Patients with Long-Term Mechanical Left Ventricular Assist Device Support in Relation to Physical Activity

by Julia Zuzanna Bura, Zuzanna Strząska-Kliś, Radosław Wilimski, Mariusz Kuśmierczyk and Daniel Karaszewski

J. Clin. Med. 2026, 15(12), 4602; https://doi.org/10.3390/jcm15124602 (registering DOI) - 13 Jun 2026

Abstract

Background/Objectives: Advanced heart failure is associated with reduced functional capacity and impaired quality of life. Left ventricular assist devices (LVADs) are increasingly used as a long-term treatment option in patients with end-stage heart failure. Despite improvements in hemodynamic function after LVAD implantation, [...] Read more.

Background/Objectives: Advanced heart failure is associated with reduced functional capacity and impaired quality of life. Left ventricular assist devices (LVADs) are increasingly used as a long-term treatment option in patients with end-stage heart failure. Despite improvements in hemodynamic function after LVAD implantation, many patients continue to experience limitations in daily functioning. The aim of this study was to evaluate the relationship between physical activity and functional status in patients with LVAD support. Methods: This study included 262 adult participants divided into four groups according to LVAD support and declared physical activity. Functional status and quality of life were assessed using the Short Form-36 Health Survey (SF-36) and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Results: Significant differences were observed between the analyzed groups in both SF-36 and MLHFQ scores. Physically active patients with LVAD achieved the most favorable results, indicating a better functional status and lower symptom burden, whereas inactive individuals demonstrated poorer outcomes. Significant correlations were found between physical activity and selected aspects of daily functioning, including walking, climbing stairs, performing household activities, and carrying groceries. Higher levels of physical activity were associated with better quality of life and fewer functional limitations. Conclusions: Physical activity may positively influence functional status and quality of life in patients with LVAD support. The findings suggest that regular physical activity should be considered an important component of rehabilitation and long-term management in patients with advanced heart failure treated with LVAD therapy. Full article

(This article belongs to the Special Issue Heart Failure and Transplant Cardiology: Latest Advances and Prospects)

13 pages, 940 KB

Open AccessArticle

Walking Uphill Aggravates Dyspnea and Dynamic Hyperinflation at Equivalent Oxygen Uptake in COPD Patients

by Ronen Reuveny, Amit Yaniv, Einat Kodesh, Tal Krasovsky, Arie Rotstein, Ariela Velner and Michael J. Segel

J. Clin. Med. 2026, 15(12), 4601; https://doi.org/10.3390/jcm15124601 (registering DOI) - 13 Jun 2026

Abstract

Background/Objectives: COPD patients often complain of severe dyspnea when walking uphill, even up a mild incline. This study aimed to determine whether the dyspnea experienced during uphill walking is disproportionate to the increased mechanical work required to overcome gravity. Methods: Fourteen [...] Read more.

Background/Objectives: COPD patients often complain of severe dyspnea when walking uphill, even up a mild incline. This study aimed to determine whether the dyspnea experienced during uphill walking is disproportionate to the increased mechanical work required to overcome gravity. Methods: Fourteen COPD patients (FEV₁ 49 ± 11% predicted) and nine healthy participants performed three symptom-limited exercise tests on a treadmill, each at a fixed grade: 1%, 2.5%, and 4% for COPD patients; and 1%, 3%, and 5% for healthy participants. Treadmill speed was increased stepwise (3 min/stage). Inspiratory capacity (IC) maneuvers were performed during the last minute of each stage. Borg dyspnea scores (0–10) at the different inclines were compared at a uniform level of oxygen uptake (iso-

\dot{V}

O₂). Results: Borg dyspnea scores by COPD patients at the highest iso-

\dot{V}

O₂ attained were significantly higher at 4% treadmill grade compared to 2.5% and compared to 1% grade (7 ± 2 vs. 5 ± 2 vs. 5 ± 2, respectively; p < 0.001 for 4% vs. 1% grade, p < 0.005 for 4% vs. 2.5%). Dynamic hyperinflation worsened with grade, as reflected by decrease in inspiratory reserve volume (IRV) at the highest common iso-

\dot{V}

O₂ attained: 798 ± 336 mL at 1% grade vs. 698 ± 325 mL at 2.5% (p < 0.004) vs. 564 ± 350 mL at 4% (p < 0.002 for 4% vs. 1%; p < 0.004 for 4% vs. 2.5%). In contrast, healthy participants showed no significant grade-dependent differences in dyspnea or IRV at iso-

\dot{V}

O₂. Conclusions: Walking uphill in itself increases breathlessness of COPD subjects at iso-

\dot{V}

O₂, suggesting that the increased dyspnea cannot be explained simply by the increased work. This phenomenon may be related to dynamic hyperinflation, which is worse at steeper inclines. Full article

(This article belongs to the Section Respiratory Medicine)

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17 pages, 582 KB

Open AccessSystematic Review

Accuracy and Outcomes of Computer-Aided Surgical Planning in Deep Circumflex Iliac Artery (DCIA) Free Flap Reconstruction of Maxillofacial Defects: A Systematic Review

by Hyo-Joon Kim, Ji-Su Oh, Kun-Woo Kim, Jun-Seong Kim and Seong-Yong Moon

J. Clin. Med. 2026, 15(12), 4600; https://doi.org/10.3390/jcm15124600 (registering DOI) - 13 Jun 2026

Abstract

Background/Objectives: Computer-aided surgical planning (CASP) technologies, including virtual surgical planning (VSP), 3D printed cutting guides, and patient-specific implants, have been increasingly applied to deep circumflex iliac artery (DCIA) free flap reconstruction of maxillofacial defects. Despite growing adoption, no systematic review has specifically [...] Read more.

Background/Objectives: Computer-aided surgical planning (CASP) technologies, including virtual surgical planning (VSP), 3D printed cutting guides, and patient-specific implants, have been increasingly applied to deep circumflex iliac artery (DCIA) free flap reconstruction of maxillofacial defects. Despite growing adoption, no systematic review has specifically evaluated their accuracy and clinical outcomes. This study aimed to comprehensively assess the impact of CASP on reconstruction accuracy, operative efficiency, flap survival, and implant rehabilitation in DCIA flap surgery. Methods: A systematic search of PubMed, Web of Science, and Google Scholar was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Studies reporting CASP-assisted DCIA free flap reconstruction with three or more patients were included. Methodological quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) checklist and the Cochrane Risk of Bias 2.0 tool for the randomized controlled trial (RCT). Results: Thirty studies (1 RCT, 13 comparative, and 16 non-comparative) involving 844 patients were included. VSP with 3D-printed cutting guides was the most frequently used technology (n = 22). Mean linear deviations between planned and actual outcomes ranged from 0.40 to 4.4 mm, with most studies reporting 0.7–2.7 mm. The sole RCT demonstrated significantly better accuracy (1.3 vs. 5.5 mm, p < 0.001) and shorter reconstruction time (16 vs. 39 min, p < 0.001) with CASP. Flap survival ranged from 90% to 100%. Conclusions: CASP technologies, particularly VSP with 3D-printed cutting guides, appear to improve the accuracy and predictability of DCIA flap reconstruction. However, the evidence base is predominantly retrospective and heterogeneous; prospective multicenter studies with standardized outcome measures are needed before definitive clinical guidelines can be established. Full article

(This article belongs to the Special Issue Contemporary Oral and Maxillofacial Surgery: Expert Consensus and Best Practices)

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22 pages, 2880 KB

Open AccessSystematic Review

Real-World Outcomes of Switching to Aflibercept 8 mg in Previously Treated Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

by Abdullah Bousamri, Mohammad Kana’an, Faisal Alharbi and Noor Alqudah

J. Clin. Med. 2026, 15(12), 4599; https://doi.org/10.3390/jcm15124599 (registering DOI) - 13 Jun 2026

Abstract

Background: Neovascular age-related macular degeneration (nAMD) remains a leading cause of irreversible central vision loss. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed management, pivotal trials enrolled exclusively treatment-naïve patients, leaving clinicians without pooled evidence to guide switching decisions in previously [...] Read more.

Background: Neovascular age-related macular degeneration (nAMD) remains a leading cause of irreversible central vision loss. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed management, pivotal trials enrolled exclusively treatment-naïve patients, leaving clinicians without pooled evidence to guide switching decisions in previously treated eyes. This systematic review and meta-analysis assessed real-world visual, anatomical, durability, and safety outcomes following switching to aflibercept 8 mg in previously treated nAMD. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, CENTRAL, Scopus, and Google Scholar through April 2026. Studies reporting switching to aflibercept 8 mg with change in best-corrected visual acuity (BCVA), central subfield thickness (CST), or treatment interval were included. Continuous outcomes were pooled using random-effects models with Hartung–Knapp–Sidik–Jonkman adjustment; proportions were estimated using generalized linear mixed models. Methodological quality was evaluated using the JBI Critical Appraisal Checklist for Case Series. Certainty of evidence was assessed using GRADE. The protocol was registered with PROSPERO (CRD420261371334). Results: Twenty-one studies met inclusion criteria. BCVA remained stable (WMD: −0.017 logMAR; 95% CI: −0.027 to −0.007; +0.83 ETDRS letters; I² = 0%). CST decreased significantly (WMD: −21.5 µm; 95% CI: −29.3 to −13.7; I² = 56.0%), and treatment intervals extended by +1.79 weeks (95% CI: +1.32 to +2.27; I² = 74.3%). Intraretinal and subretinal fluid each resolved in 37.5% of eyes. Intraocular inflammation was rare across 9959 treated eyes, though this pool was not restricted to switched eyes, with no confirmed retinal vasculitis. Sensitivity analyses confirmed robustness across all co-primary estimates. GRADE certainty was low for BCVA and very low for CST and treatment interval. Conclusions: Low-certainty evidence suggests that switching to aflibercept 8 mg preserves visual acuity, while very-low-certainty evidence suggests reductions in central subfield thickness and modest extension of treatment intervals. Intraocular inflammation was rare, though safety denominators included non-switch eyes. These findings provide preliminary pooled estimates to inform switch decisions in previously treated eyes. Full article

(This article belongs to the Section Ophthalmology)

18 pages, 465 KB

Open AccessReview

Cardiac Rehabilitation and Cognitive Impairment: Elective Affinities or Fatal Attraction

by Valeria Visco, Francesco Loria, Antonio Squillante, Francesca Palmieri, Federica Piani, Ilaria Fucile, Carmine Izzo, Maria Rosaria Rusciano, Cristina Gatto, Rónán O’Caoimh, David William Molloy, Costantino Mancusi, Giorgia Bruno, Nicola Virtuoso, Carmine Vecchione and Michele Ciccarelli

J. Clin. Med. 2026, 15(12), 4598; https://doi.org/10.3390/jcm15124598 (registering DOI) - 13 Jun 2026

Abstract

Cardiac rehabilitation (CR) is strongly recommended in secondary cardiovascular prevention; indeed, in patients after cardiac surgery or with coronary artery disease or heart failure, this intervention is recommended to decrease mortality, morbidity, and disability, and to improve quality of life and cardiorespiratory fitness. [...] Read more.

Cardiac rehabilitation (CR) is strongly recommended in secondary cardiovascular prevention; indeed, in patients after cardiac surgery or with coronary artery disease or heart failure, this intervention is recommended to decrease mortality, morbidity, and disability, and to improve quality of life and cardiorespiratory fitness. Moreover, each step of the cardiovascular continuum denotes a potential risk factor for the progression of cognitive frailty; this interaction is highly prevalent, affecting approximately one-third of all patients in cardiology settings. For these reasons, CR should consider the patient’s cognitive domain; however, cognitive assessment is still rarely integrated into standard CR protocols. Therefore, this comprehensive review presents current evidence and recent updates on the interaction between CR and cognitive impairment, focusing on physiological mechanisms, core components, benefits, and strategies for implementing CR in patients with cognitive frailty to optimize recovery and prognosis. Full article

(This article belongs to the Special Issue The Role of Cardiac Rehabilitation After Myocardial Infarction, Coronary Artery Bypass Surgery, and in Other Cardiac Diseases)

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Graphical abstract

21 pages, 694 KB

Open AccessReview

The Oxygen Imperative: Cardiorespiratory Fitness, Dose-Dependent Exercise Thresholds, and Longevity—A Narrative Review

by Dragos Cozma, Dan Gaita, Simina Crisan, Cristina Tudoran, Andreea Simina Dumitrescu and Cristina Văcărescu

J. Clin. Med. 2026, 15(12), 4597; https://doi.org/10.3390/jcm15124597 (registering DOI) - 13 Jun 2026

Abstract

Background: The relationship between physical exercise and human longevity constitutes one of the most consequential intersections in contemporary preventive medicine. Although international guidelines recommend 150 min of moderate-intensity exercise weekly, growing evidence suggests that the architecture of optimal exercise is far more [...] Read more.

Background: The relationship between physical exercise and human longevity constitutes one of the most consequential intersections in contemporary preventive medicine. Although international guidelines recommend 150 min of moderate-intensity exercise weekly, growing evidence suggests that the architecture of optimal exercise is far more complex, encompassing dose, modality, timing across the lifespan, and the paradox risks imposed by extreme endurance. Methods: We included in this narrative review landmark cohort studies, randomized controlled trials, meta-analyses, and expert physiological frameworks published in high-impact cardiovascular, sports medicine, and longevity journals from 1966 to 2024. Results: Cardiorespiratory fitness (CRF), indexed by maximal oxygen uptake (VO₂ max), demonstrates the strongest and most linear dose–response relationship with all-cause mortality identified in preventive medicine, with every 1 metabolic equivalent of task (MET) increment associated with a 12–15% reduction in mortality risk. The optimal dose of vigorous-intensity exercise follows a J-shaped dose–response curve: 3–5 sessions per week generating 1–2.4 h of vigorous activity is associated with the lowest all-cause mortality risk in large prospective cohorts, whereas chronic extreme endurance exercise incurs measurable atrial remodeling, patchy myocardial fibrosis, and a 5.3-fold increase in the risk of atrial fibrillation. The importance of exercise types shifts profoundly across the lifespan, transitioning from aerobic capacity effort in the third decade to resistance training in the seventh decade and neuromuscular stability in the eighth. Based on our interpretation of the available evidence, we propose a structured, personalized four-step exercise pathway integrating CRF assessment, lifespan-adapted prescription, lifestyle co-interventions, and periodic reassessment. Conclusions: Among currently available lifestyle interventions, regular exercise is consistently associated with some of the largest and most reproducible reductions in all-cause and cardiovascular mortality observed in prospective cohort data, while remaining accessible and cost-effective. Full article

(This article belongs to the Special Issue Advances in Clinical Exercise for Health)

10 pages, 523 KB

Open AccessArticle

The Prevalence and Diagnostic of Silent Ischemic Heart Disease in Polish Kidney Transplant Candidates

by Piotr B. Kuczera, Aleksandra Grzmil, Szymon Domagała, Jakub Milczarek, Anna Walukiewicz, Andrzej Więcek and Aureliusz Kolonko

J. Clin. Med. 2026, 15(12), 4596; https://doi.org/10.3390/jcm15124596 (registering DOI) - 13 Jun 2026

Abstract

Background/Objectives: Patients with chronic kidney disease (CKD) have an increased risk of ischemic heart disease (IHD). Some discrepancies exist between cardiological and nephrological guidelines regarding the extent of diagnostic procedures in CKD patients who are candidates for kidney transplantation. The aim of [...] Read more.

Background/Objectives: Patients with chronic kidney disease (CKD) have an increased risk of ischemic heart disease (IHD). Some discrepancies exist between cardiological and nephrological guidelines regarding the extent of diagnostic procedures in CKD patients who are candidates for kidney transplantation. The aim of this study was to assess the cardiac status of these patients after cardiological checkup. Methods: The present study included all kidney transplant candidates referred to the Regional Qualification Center between January 2021 and February 2024. We characterized the group of patients in whom IHD was diagnosed during the cardiological checkup. Results: Among 346 patients, IHD was newly identified in 44 (12.7%) subjects. These patients were significantly older [median 62.9 (51.9–65.4) vs. 47.2 (36.8–57.9) years; p < 0.001], had longer dialysis vintage [median 20 (12.5–42) vs. 14 (6–31) months; p < 0.05] and were more frequently diabetic (29.6 vs. 16.9%, p < 0.05) than the rest of the study cohort. Of note, they were also characterized by significantly more frequent manifestation of atherosclerosis lesions visualized using routine imaging methods (i.e., chest X-ray and abdominal aorta and iliac artery visualization). The stepwise logistic regression analysis revealed that age [OR 1.05 (1.02–1.09); p <0.01] and the ad hoc atherosclerotic score [OR 1.88 (1.27–2.77); p < 0.001] independently predicted the diagnosis of IHD during the cardiological qualification of potential kidney transplant candidates. Conclusions: During the cardiological examination, IHD was diagnosed in a substantial number of kidney transplant candidates. The presence of atherosclerotic lesions detected by routine noninvasive vascular system imaging methods may suggest the need for extending IHD diagnostics even in relatively young patients without clinical symptoms. Full article

(This article belongs to the Special Issue Clinical Management of Patients Before and After Kidney Transplantation)

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16 pages, 1990 KB

Open AccessArticle

Low-Intensity Pulsed Ultrasound Enhances Intramembranous Bone Healing in a Critical-Size Bone Defect of the Rat Calvaria

by Darian Volarić, Gordana Žauhar, Jie Chen, Ana Terezija Jerbić Radetić, Rok Kostanjšek, Hrvoje Omrčen, Silvije Šegulja, Edi Rođak and Olga Cvijanović Peloza

J. Clin. Med. 2026, 15(12), 4595; https://doi.org/10.3390/jcm15124595 (registering DOI) - 13 Jun 2026

Abstract

Objectives: Low-intensity pulsed ultrasound (LIPUS) has been widely utilized as a biophysical modality accelerating fracture healing, particularly in bones undergoing endochondral ossification. However, its efficacy in facilitating intramembranous ossification remains unclear. This study aimed to evaluate the effects of LIPUS and autologous [...] Read more.

Objectives: Low-intensity pulsed ultrasound (LIPUS) has been widely utilized as a biophysical modality accelerating fracture healing, particularly in bones undergoing endochondral ossification. However, its efficacy in facilitating intramembranous ossification remains unclear. This study aimed to evaluate the effects of LIPUS and autologous bone (AB) on bone healing in a critical-size bone defect (CSBD) model of the rat calvaria. Methods: We performed micro-computed tomography (micro-CT) and immunohistochemical TNF-α analysis on bone specimens to assess osteogenesis. Results: Micro-CT demonstrated significant increases in newly formed bone on day 30 compared with days 7 and 15 across all groups (p < 0.001). The highest bone volume was observed in the AB group (26.83%), followed by the LIPUS group (23.74%), and the lowest in the control (15.85%). Immunohistochemical analysis revealed significantly higher TNF-α expression on day 7 in the control group (172.0 ± 1.1) than in the AB (133.8 ± 0.9) and LIPUS (125.2 ± 0.8) groups (p < 0.001). On day 15, TNF-α expression was significantly higher in the LIPUS group (137.7 ± 1.3) than in both the AB (134.2 ± 1.8) and control (126.6 ± 2.2) groups (p < 0.001). At day 30, TNF-α levels in the LIPUS group (147.6 ± 1.9) remained significantly higher than in the control group (115.8 ± 0.9) (p < 0.001), with no significant difference compared to the AB group (146.3 ± 0.8). Conclusions: Although AB grafting achieved the greatest bone volume, LIPUS demonstrated considerable regenerative potential and may represent a promising non-invasive therapeutic approach to enhance intramembranous bone regeneration. Full article

(This article belongs to the Special Issue Orthopaedic Trauma and Bone Healing: Recent Advances and Future Perspectives)

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13 pages, 19900 KB

Open AccessArticle

The Pelvic INFIX Technique for Unstable Anterior Pelvic Ring Fractures: Clinical Outcomes, Radiographic Results, and Complications

by Vasileios Athanasiou, Michalis Kroustalakis, Fotios Panagopoulos, Panagiotis Antzoulas, Vasileios Papathanidis and Vasileios Giannatos

J. Clin. Med. 2026, 15(12), 4594; https://doi.org/10.3390/jcm15124594 (registering DOI) - 13 Jun 2026

Abstract

Background: Unstable pelvic ring injuries often require surgical stabilization to restore pelvic ring integrity. The anterior subcutaneous internal fixator, or pelvic INFIX, has emerged as an alternative to external fixation and open anterior fixation. This study evaluated the functional, radiographic, and complication-related outcomes [...] Read more.

Background: Unstable pelvic ring injuries often require surgical stabilization to restore pelvic ring integrity. The anterior subcutaneous internal fixator, or pelvic INFIX, has emerged as an alternative to external fixation and open anterior fixation. This study evaluated the functional, radiographic, and complication-related outcomes of INFIX fixation for unstable anterior pelvic ring injuries. Methods: We retrospectively reviewed 21 adult patients treated with anterior pelvic INFIX for unstable anterior pelvic ring fractures, with or without posterior fixation, at a Level 1 Trauma Center between 2017 and 2024. Fractures were classified according to the AO/OTA system. Functional outcomes were assessed using the Iowa Pelvic Score and Short Form-12 questionnaire. Radiographic outcomes were evaluated according to Tornetta and Matta criteria. Complications were recorded throughout follow-up. The INFIX device was routinely removed 6 months postoperatively. Results: The cohort included 15 males and six females, with a mean age of 42.5 ± 11.1 years. Mean Injury Severity Score was 25.3 ± 9.6, and mean follow-up after implant removal was 31 (IQR 28–34) months. The mean Iowa Pelvic Score was 80.2 ± 7.4, indicating an overall good functional outcome. Mean SF-12 physical and mental scores were 49.2 ± 3.5 and 48.3 ± 7.9, respectively. Radiographic outcomes were excellent in eight patients, good in 11, and fair in two. Complications included postoperative hemorrhage, implant loosening, heterotopic ossification, and three cases of lateral femoral cutaneous nerve (LFCN) injury. Conclusions: INFIX fixation appears to be a reliable minimally invasive option for unstable anterior pelvic ring injuries, providing satisfactory mid-term functional and radiographic outcomes with an acceptable complication profile. Full article

(This article belongs to the Special Issue Advances in Trauma and Orthopedic Surgery: 3rd Edition)

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12 pages, 584 KB

Open AccessArticle

Erector Spinae Plane Block Versus Thoracic Paravertebral Block in Laparoscopic Cholecystectomy: A Randomized Controlled Study

by Özlem Turhan, Zerrin Sungur, Müşerref Beril Dinçer, Meltem Savran Karadeniz, Esra Saka, Hacer Ayşen Yavru, Reyhan Nil Kırşan and Nükhet Sivrikoz

J. Clin. Med. 2026, 15(12), 4593; https://doi.org/10.3390/jcm15124593 (registering DOI) - 13 Jun 2026

Abstract

Objectives: This randomized, single-blind study aimed to compare the effects of ultrasound-guided erector spinae plane block (ESPB), thoracic paravertebral block (TPVB) and intravenous (IV) analgesia on postoperative pain, opioid consumption and quality of recovery in patients undergoing laparoscopic cholecystectomy (LC). Methods: [...] Read more.

Objectives: This randomized, single-blind study aimed to compare the effects of ultrasound-guided erector spinae plane block (ESPB), thoracic paravertebral block (TPVB) and intravenous (IV) analgesia on postoperative pain, opioid consumption and quality of recovery in patients undergoing laparoscopic cholecystectomy (LC). Methods: A total of 120 adult patients (ASA I-III) scheduled for elective LC were randomized into three groups: ESPB (GI), TPVB (GII) and IV analgesia (GIII). Bilateral ESPB or TPVB was performed preoperatively; then all patients received standardized general anesthesia and postoperative analgesia including paracetamol, tenoxicam and IV tramadol via patient-controlled analgesia. The primary outcome was 24 h tramadol consumption. Secondary outcomes included pain scores, rescue analgesia requirement, patient satisfaction, postoperative nausea and vomiting, time to first ambulation, length of hospital stay and Quality of Recovery-15 (QoR-15) scores. Results: Twenty-four-hour tramadol consumption was significantly higher in GIII (135.78 ± 22.73 mg) compared with GI (101.05 ± 26.99 mg) and GII (95.67 ± 31.49 mg) (p < 0.001), with no difference between GI and GII. Both static and dynamic pain scores were lower in GI and GII compared with GIII at most time points. Rescue analgesia requirement and patient dissatisfaction were significantly higher in GIII. QoR-15 scores were significantly improved in GI and GII compared with GIII (p < 0.001), while no difference was observed between the regional techniques. Block performance time was shorter with ESPB than TPVB (p < 0.001). No complications were reported. Conclusions: ESPB and TPVB provided effective analgesia and improved recovery after LC compared with IV analgesia alone. Both regional techniques may be considered as components of multimodal analgesia after LC. Full article

(This article belongs to the Section Anesthesiology)

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22 pages, 6825 KB

Open AccessArticle

Clinical Prognostic Modeling and Paired Blood–CSF Metabolomic Profiling for Outcome Prediction in Isolated Moderate-to-Severe Traumatic Brain Injury: Implications for Neurocritical Care Management

by Zhuoying Du, Qifang Chen, Yuzhuo Wang, Pengfei Fu, Jin Hu, Gang Wu and Weijian Yang

J. Clin. Med. 2026, 15(12), 4592; https://doi.org/10.3390/jcm15124592 (registering DOI) - 13 Jun 2026

Abstract

Objectives: This study aimed to develop a prognostic model for isolated moderate-to-severe traumatic brain injury (TBI) (Glasgow Coma Scale [GCS] ≤ 12) using readily available variables and to explore paired blood–cerebrospinal fluid (CSF) metabolomic signatures. Methods: Consecutive TBI patients admitted between January 2019 [...] Read more.

Objectives: This study aimed to develop a prognostic model for isolated moderate-to-severe traumatic brain injury (TBI) (Glasgow Coma Scale [GCS] ≤ 12) using readily available variables and to explore paired blood–cerebrospinal fluid (CSF) metabolomic signatures. Methods: Consecutive TBI patients admitted between January 2019 and June 2025 were retrospectively analyzed. Multivariate logistic regression with bootstrap internal validation identified predictors of 6-month unfavorable outcome and in-hospital mortality. Untargeted metabolomics was performed on paired blood and CSF samples from 30 matched male patients. Results: Among 405 patients, 266 (65.7%) had unfavorable outcomes and 54 (13.3%) died in hospital. Rotterdam CT Score (odds ratio [OR] 10.59, 95% confidence interval [CI] 6.19–18.14), initial lactate (OR 1.81, 95% CI 1.38–2.36), and blood glucose (OR 1.40, 95% CI 1.21–1.64) predicted unfavorable outcome (area under the receiver operating characteristic curve [AUC] 0.97). GCS motor score (OR 0.50, 95% CI 0.37–0.66), initial lactate (OR 1.57, 95% CI 1.31–1.91), and follow-up lactate (OR 1.57, 95% CI 1.34–1.88) predicted mortality (AUC 0.96). Blood metabolomics revealed enrichment in energy and lipid metabolism pathways. CSF metabolomics highlighted neurotransmitter pathway dysregulation and neuroinflammatory markers, with depleted kynurenic acid in both biofluids. Conclusions: Readily available admission variables enable early bedside risk stratification in TBI. Metabolomic profiling links unfavorable outcomes to systemic energy–lipid dysregulation and central neuroinflammatory–neurotransmitter disturbances, with the tryptophan–kynurenine axis as a potential therapeutic target for neuroprotective strategies. Full article

(This article belongs to the Special Issue Management Strategies for Traumatic Brain Injury in Neurocritical Care Unit)

11 pages, 1187 KB

Open AccessArticle

Bariatric Surgery Utilization Trends in the United States Following COVID-19 and the 2022 ASMBS/IFSO Guideline Expansion: An Interrupted Time Series Analysis

by Abdulrahman A. Alsuhibani

J. Clin. Med. 2026, 15(12), 4591; https://doi.org/10.3390/jcm15124591 (registering DOI) - 13 Jun 2026

Abstract

Background: In the US, obesity is still a serious public health issue. Bariatric surgery utilization has recently been influenced by the COVID-19 pandemic and the 2022 American Society for Metabolic and Bariatric Surgery (ASMBS)/International Federation for the Surgery of Obesity and Metabolic Disorders [...] Read more.

Background: In the US, obesity is still a serious public health issue. Bariatric surgery utilization has recently been influenced by the COVID-19 pandemic and the 2022 American Society for Metabolic and Bariatric Surgery (ASMBS)/International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) guideline expansion. The combined effects of these events on national utilization trends remain unclear. Methods: We conducted a retrospective longitudinal study using electronic medical record data from the TriNetX network, including adults aged ≥18 years from 2018 through 2024. Primary bariatric procedures were identified using validated CPT and ICD codes. Quarterly surgery rates per 100,000 adults were calculated using the number of unique adults with at least one healthcare encounter per quarter as the denominator. Level and slope changes related to the start of COVID-19 (Q2 2020) and the application of the 2022 ASMBS guidelines (Q1 2022) were evaluated using interrupted time series models. Procedure-type distributions were also evaluated. Results: A total of 215,072 procedures were identified. Utilization was stable before Q2 2020, when a significant decline occurred following the onset of COVID-19. Rates recovered through 2021. After Q1 2022, a modest immediate increase was observed, followed by a sustained downward trend through 2024. Sleeve gastrectomy accounted for approximately two-thirds of procedures throughout the study period. Conclusions: Bariatric surgery utilization was markedly disrupted by COVID-19 and showed limited sustained growth after guideline expansion. These patterns might be a reflection of more general changes in the management of obesity, such as the growing accessibility of medication. Full article

(This article belongs to the Special Issue Clinical Advances in Obesity and Bariatric Surgery—2nd Edition)

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19 pages, 846 KB

Open AccessArticle

Clinical Determinants of Halitosis in Elderly Patients with Complete, Partial, and Fixed Prosthetic Rehabilitation

by Romina Georgiana Bita, Otilia Cornelia Boloș, Edida Maghet, Adrian Boloș, Raluca Briceag and Bogdan Andrei Bumbu

J. Clin. Med. 2026, 15(12), 4590; https://doi.org/10.3390/jcm15124590 (registering DOI) - 12 Jun 2026

Abstract

Background/Objectives: Halitosis in geriatric patients is multifactorial, but the joint contribution of prosthetic rehabilitation type and polypharmacy after routine dental procedures has rarely been quantified. We investigated how prosthesis type, polypharmacy, and salivary function were associated with volatile sulfur compound (VSC) burden [...] Read more.

Background/Objectives: Halitosis in geriatric patients is multifactorial, but the joint contribution of prosthetic rehabilitation type and polypharmacy after routine dental procedures has rarely been quantified. We investigated how prosthesis type, polypharmacy, and salivary function were associated with volatile sulfur compound (VSC) burden and self-perceived halitosis in elderly dental patients. Methods: This cross-sectional study enrolled 88 patients aged ≥65 years, four weeks after completing routine dental procedures. Participants were stratified into three groups: complete denture wearers (n = 30), partial removable denture wearers (n = 28), and fixed prostheses/implants (n = 30). We measured unstimulated salivary flow rate (uSFR), tongue coating index (TCI), denture biofilm index, total VSCs (Halimeter^®), organoleptic score (0–5), and self-perceived halitosis. Polypharmacy, comorbidities, and the Geriatric Oral Health Assessment Index (GOHAI) were recorded. Analyses included one- and two-way ANOVA, Spearman correlations, theory-informed multivariable linear and logistic regression, exploratory mediation analysis, and ROC curves. Results: Forty-two participants (47.7%) reported halitosis. Mean VSC differed across groups (complete dentures 278.2 ± 38.6 ppb; partial 211.2 ± 46.3 ppb; fixed 164.4 ± 43.9 ppb; ANOVA p < 0.001). uSFR correlated inversely with VSC (ρ = −0.61, p < 0.001) and TCI correlated positively (ρ = 0.56, p < 0.001). A significant prosthesis × polypharmacy interaction was observed (F = 3.74, p = 0.029, η²_p = 0.082): polypharmacy was associated with higher VSC most clearly among partial and fixed prostheses wearers, whereas complete denture wearers showed high VSC levels regardless of polypharmacy status. Exploratory mediation findings were consistent with partial indirect association, with 45.9% of the polypharmacy–VSC association statistically explained by reduced uSFR; however, the cross-sectional design precludes causal or temporal interpretation. The full multivariable model showed apparent discrimination for self-perceived halitosis (AUC = 0.92), while the simplified four-item chairside composite model showed AUC = 0.89; neither estimate was optimism-corrected or externally validated. Conclusions: In elderly post-procedure patients, complete denture wearing, polypharmacy, and salivary hypofunction were independently and jointly associated with higher halitosis burden. Reduced salivary flow was consistent with a partial indirect statistical pathway in the polypharmacy–VSC association, supporting hydration counseling and meticulous prosthesis hygiene as low-cost geriatric interventions. Sensitivity analyses excluding implant-supported restorations, participants with MMSE scores of 24–26, and expanded mediation models including TCI and biofilm/plaque did not materially change the main inference. Full article

(This article belongs to the Special Issue Clinical Updates on Prosthodontics)

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14 pages, 1329 KB

Open AccessArticle

Comparison of Early Postoperative Recovery and Radiologic Outcomes Between Microscopic and Unilateral Biportal Endoscopic Posterior Cervical Foraminotomy for Cervical Radiculopathy

by Sang Youp Han, Sang Hyub Lee, Jae Won Jang, Choon Keun Park and Dong Geun Lee

J. Clin. Med. 2026, 15(12), 4589; https://doi.org/10.3390/jcm15124589 (registering DOI) - 12 Jun 2026

Abstract

Objective: This study aimed to compare the clinical and radiological outcomes between microscopic and unilateral biportal endoscopic (UBE) posterior cervical foraminotomy (PCF). Methods: This study included 73 patients who underwent microscopic PCF (n = 40) or UBE PCF (n [...] Read more.

Objective: This study aimed to compare the clinical and radiological outcomes between microscopic and unilateral biportal endoscopic (UBE) posterior cervical foraminotomy (PCF). Methods: This study included 73 patients who underwent microscopic PCF (n = 40) or UBE PCF (n = 33) for single-level cervical foraminal disc herniation or stenosis between January 2018 and December 2021. Clinical outcomes were measured using the Visual Analog Scale (VAS) and Neck Disability Index (NDI). Radiologic outcomes were evaluated with cervical range of motion (ROM) using computed tomography and flexion-extension dynamic radiography. Results: The mean follow-up period for microscopic and UBE PCF was 33.0 ± 7.6 months and 29.9 ± 5.9 months, respectively. The postoperative neck VAS until postoperative 2 weeks was significantly lower in the UBE PCF group than in the microscopic PCF group (p < 0.05). The estimated blood loss and operative time were significantly lower in the UBE PCF group than in the microscopic PCF group, while the length of hospital stay was numerically shorter but did not reach statistical significance. The two groups had no significant difference in the NDI on the preoperative and postoperative 3 months. The recurrence occurred in 1 patient (2.5%) of the microscopic PCF group and 1 patient (3%) of the UBE PCF group. The revision surgery was performed in 2 patients (5%) of the microscopic PCF group and in 1 patient of the UBE PCF group. There were no significant differences in motion and instability between the two groups. Conclusions: Both microscopic and UBE PCF are effective and safe procedures for treating cervical radiculopathy due to cervical foraminal disc herniation or stenosis. The UBE approach may provide advantages mainly in early postoperative recovery, including lower early postoperative neck pain, while long-term clinical and radiologic outcomes appear comparable to those of microscopic PCF. Full article

(This article belongs to the Special Issue Clinical Research on Minimally Invasive Spine Surgery)

17 pages, 45996 KB

Open AccessArticle

Drone-Induced Midfacial Blast Injuries: Early Definitive Reconstruction and 5-Year Outcomes from a Single-Center Cohort

by Anna Poghosyan, Martin Misakyan, Gurgen Mkhitaryan, Davit Minasyan, Irina Malkhasyan, Hayk Petrosyan, Anna Frangulyan, Aren Bablumyan, Armen Minasyan and Armen Muradyan

J. Clin. Med. 2026, 15(12), 4588; https://doi.org/10.3390/jcm15124588 (registering DOI) - 12 Jun 2026

Abstract

Background: Modern warfare has introduced novel mechanisms of injury, particularly drone-induced blast trauma, resulting in complex craniomaxillofacial injuries. These injuries differ substantially from typical ballistic wounds and require adapted surgical strategies. This study was conducted to evaluate the clinical characteristics, management approaches, and [...] Read more.

Background: Modern warfare has introduced novel mechanisms of injury, particularly drone-induced blast trauma, resulting in complex craniomaxillofacial injuries. These injuries differ substantially from typical ballistic wounds and require adapted surgical strategies. This study was conducted to evaluate the clinical characteristics, management approaches, and long-term outcomes of midfacial blast injuries. Methods: A retrospective analytical study was conducted on 41 patients with drone-induced midfacial blast injuries treated at a tertiary referral center in Armenia following the 2020 Nagorno-Karabakh War. All patients underwent surgical management after initial stabilization and were followed for 5 years. Clinical outcomes, complications, and reconstructive needs were assessed. Results: All patients presented with comminuted midfacial fractures, which were frequently associated with polytrauma (87.8%). Burns were observed in 82.9% of cases. Surgical management included radical debridement and early definitive osteosynthesis using titanium fixation systems. No cases of postoperative osteomyelitis, bone sequestration, or implant failure were observed during the 5-year follow-up period. Patients with extensive soft tissue defects, particularly nasal and lip amputations, required multiple reconstructive procedures. Long-term follow-up revealed progressive soft tissue thinning over titanium meshes, especially in the zygomatico-orbital region, necessitating secondary interventions such as lipofilling. Conclusions: Drone-induced midfacial blast injuries represent a distinct and severe form of trauma. Early definitive reconstruction following adequate debridement was associated with favorable outcomes. However, soft tissue reconstruction remains challenging and often requires staged procedures. Long-term follow-up is essential to manage delayed complications and optimize aesthetic outcomes. Full article

(This article belongs to the Special Issue Recent Advances in Prevention, Management, and Rehabilitation of Head and Neck Injuries)

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