Journal of Clinical Medicine

20 pages, 1990 KB

Open AccessArticle

Accuracy of Combined Osteotomy Guides and Patient-Specific Implants in Le Fort I Segmental Osteotomy Requiring Alveolar Bone Reduction

by Xinyu Xu, Ling Wu, Zili Li and Xiaojing Liu

J. Clin. Med. 2026, 15(18), 7316; https://doi.org/10.3390/jcm15187316 (registering DOI) - 20 Sep 2026

Abstract

Background: Segmental Le Fort I osteotomy combined with interdental alveolar bone reduction is a technically challenging procedure, and the accuracy of patient-specific implants (PSIs) in this setting has not been well established. This study aimed to assess the three-dimensional (3D) repositioning accuracy [...] Read more.

Background: Segmental Le Fort I osteotomy combined with interdental alveolar bone reduction is a technically challenging procedure, and the accuracy of patient-specific implants (PSIs) in this setting has not been well established. This study aimed to assess the three-dimensional (3D) repositioning accuracy and safety of 3D-printed osteotomy guides used in conjunction with PSIs for this complex surgical procedure. Materials and Methods: This retrospective consecutive case series included 19 patients who underwent segmental Le Fort I osteotomy with alveolar bone reduction in the premolar region. For all patients, 3D-printed osteotomy guides and PSIs were designed using virtual surgical planning (VSP). Postoperative CBCT reconstruction models were superimposed on the VSP models to assess accuracy based on 3D deviations of skeletal and dental landmarks, angular discrepancies, and dental arch morphology. Residual intersegmental alveolar gaps and perioperative complications were also evaluated. Results: Signed and absolute coordinate deviations of all landmarks were within the 2 mm reference margin. Signed coordinate deviations differed significantly among the X-, Y-, and Z-axes (p < 0.05), with the X-axis showing the smallest mean deviation (0.064 ± 0.753 mm). The overall Euclidean spatial error was 1.477 ± 0.519 mm. Anterior maxillary segments exhibited significantly greater sagittal and vertical deviations than posterior segments (p < 0.05). The overall mean residual intersegmental alveolar gap was 0.681 ± 0.153 mm, with the buccal gap at the root apex significantly larger than the corresponding palatal gap (p < 0.05). Two minor dentin injuries occurred, neither of which resulted in clinical pulpal or periodontal complications during the available follow-up. Conclusions: The combined use of osteotomy guides and PSIs facilitates accurate 3D maxillary repositioning in segmental Le Fort I osteotomy involving alveolar bone reduction. Full article

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

25 pages, 1641 KB

Open AccessFeature PaperArticle

Integrated Cardio–Renal–Metabolic Risk Profiling in Patients with Type 2 Diabetes: A Machine Learning-Assisted Cross-Sectional Analysis

by Bianca-Lăcrimioara Petca, Paula-Alexandra Popovici, Andreea Diana Igna, Timea Claudia Ghitea and Mihaela Simona Popoviciu

J. Clin. Med. 2026, 15(18), 7315; https://doi.org/10.3390/jcm15187315 (registering DOI) - 20 Sep 2026

Abstract

Background/Objectives: Type 2 diabetes mellitus (T2DM) is characterized by overlapping cardiovascular, renal, metabolic, and hepatic-risk abnormalities. We characterized this integrated phenotype, examined SCORE2-Diabetes gradients, and assessed whether routinely available variables could classify established atherosclerotic cardiovascular disease (ASCVD). Methods: This cross-sectional study included 232 [...] Read more.

Background/Objectives: Type 2 diabetes mellitus (T2DM) is characterized by overlapping cardiovascular, renal, metabolic, and hepatic-risk abnormalities. We characterized this integrated phenotype, examined SCORE2-Diabetes gradients, and assessed whether routinely available variables could classify established atherosclerotic cardiovascular disease (ASCVD). Methods: This cross-sectional study included 232 consecutive adults with T2DM. SCORE2-Diabetes tertiles in the full cohort were analyzed descriptively, and a sensitivity analysis was restricted to participants aged 40–69 years without established ASCVD or severe target-organ damage. FIB-4 was recalculated from age, aspartate aminotransferase, alanine aminotransferase, and platelet count. Elastic-net logistic regression, random forest, and gradient boosting were evaluated using nested stratified five-fold cross-validation, with all preprocessing and hyperparameter tuning confined to the training folds. Results: Established ASCVD was present in 49 participants (21.1%), corresponding to 4.45 events per candidate predictor. The SCORE2-Diabetes-eligible sensitivity subgroup included 118 participants (50.9%); 72.9% were in the ≥20% 10-year-risk category. FIB-4 was available for 231 participants (median 1.26 [IQR 0.96–1.80]). Nested cross-validated ROC AUCs were 0.675 (95% CI 0.582–0.763) for elastic-net logistic regression, 0.670 (0.581–0.754) for random forest, and 0.674 (0.589–0.752) for gradient boosting; balanced accuracies were 65.4%, 62.8%, and 56.2%, respectively. Conclusions: The cohort had a high and heterogeneous cardio–renal–metabolic burden. SCORE2-Diabetes findings from the full cohort are descriptive because the score is not intended for patients with established ASCVD or severe target-organ damage. The machine-learning models showed only modest, internally validated discrimination and are not suitable for clinical deployment without larger prospective cohorts and external validation. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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13 pages, 3494 KB

Open AccessArticle

Multi-Center Analysis of the Association Between Meteorological Factors and Aneurysmal Subarachnoid Hemorrhage Using Logistic and Machine Learning Models in Upstate New York

by Avi A. Gajjar, Aditya D. Goyal, Ali Naqvi, Samhita Bheemireddy, Amanda Custozzo, Vinay Jaikumar, Adnan H. Siddiqui, Alan S. Boulos, John C. Dalfino and Alexandra R. Paul

J. Clin. Med. 2026, 15(18), 7314; https://doi.org/10.3390/jcm15187314 (registering DOI) - 20 Sep 2026

Abstract

Introduction: Ruptured intracranial aneurysms (RIAs) are a significant cause of morbidity and mortality. While individual-level risk factors for aneurysmal subarachnoid hemorrhage (aSAH) are well established, the influence of meteorological variables has been widely debated but remains unclear. Methods: We retrospectively analyzed 1504 endovascularly [...] Read more.

Introduction: Ruptured intracranial aneurysms (RIAs) are a significant cause of morbidity and mortality. While individual-level risk factors for aneurysmal subarachnoid hemorrhage (aSAH) are well established, the influence of meteorological variables has been widely debated but remains unclear. Methods: We retrospectively analyzed 1504 endovascularly treated intracranial aneurysm cases from two stroke centers (2018 to 2024). We matched daily weather data to presentation dates. We used variance inflation factor (VIF) analysis to remove collinear features. Multivariable logistic regression models were adjusted for age and sex. We developed extreme gradient boosting (XGBoost) models using weather variables alone and in combination with demographic covariates (age, sex, race, smoking status, and family history). Results: Of 1504 cases, 377 (25.1%) presented with rupture. In univariate logistic regression, greater humidity (odds ratio [OR] 0.988 per 1% relative humidity, 95% confidence interval [CI] 0.979 to 0.998, p = 0.0135) and greater ultraviolet (UV) index (OR 0.951 per index unit, 95% CI 0.914 to 0.990, p = 0.0146) were associated with reduced odds of rupture, whereas greater snow depth (OR 1.360 per inch, 95% CI 1.068 to 1.731, p = 0.0126) and advanced moon phase (OR 1.589 per full lunar cycle, 95% CI 1.064 to 2.373, p = 0.0237) were associated with increased odds. On multivariable analysis, only female sex remained protective (OR 0.605, 95% CI 0.386 to 0.949, p = 0.0285), and greater sea level pressure trended toward lower odds of rupture without reaching significance (OR 0.962, p = 0.0523). Findings were consistent in a full-cohort, center-adjusted sensitivity analysis. The weather-only XGBoost model yielded an area under the receiver operating characteristic curve (AUC) of 0.560 and a recall of 78%, which improved to an AUC of 0.590 and a recall of 83% after adding demographic variables. SHapley Additive exPlanations (SHAP) analysis identified precipitation and cloud cover as key meteorological features. Conclusions: Several weather variables correlated with rupture risk in univariate analysis, but overall predictive value was limited. Machine learning improved sensitivity while confirming patient features as the dominant contributors. Weather on the day of presentation was not significantly associated with rupture. Full article

(This article belongs to the Section Clinical Neurology)

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32 pages, 1593 KB

Open AccessReview

GLP-1 Receptor Agonists and Tirzepatide in Men Seeking Fertility: A Structured Narrative Review and Proposed Clinical Framework

by Aris Kaltsas, Vasileios Gkioxaris, Timoleon Giannakas, Athanasios Zachariou, Fotios Dimitriadis, Nikolaos Sofikitis and Michael Chrisofos

J. Clin. Med. 2026, 15(18), 7313; https://doi.org/10.3390/jcm15187313 (registering DOI) - 20 Sep 2026

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide are increasingly used to treat obesity and type 2 diabetes in men of reproductive age, but practical guidance for counseling men planning fatherhood remains limited. This structured narrative [...] Read more.

Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide are increasingly used to treat obesity and type 2 diabetes in men of reproductive age, but practical guidance for counseling men planning fatherhood remains limited. This structured narrative review distinguishes endocrine, semen, sexual-function, and clinical fertility outcomes. In metabolically impaired men, studies largely involving liraglutide or semaglutide report increases in total testosterone; free-testosterone findings are inconsistent, and the available small short-term studies did not show the marked gonadotropin suppression expected with exogenous testosterone. Some studies report favorable changes in semen parameters, but samples are small, populations heterogeneous, and medication effects cannot be separated reliably from weight loss. The present search identified no adequately powered GLP-1-specific prospective study that prespecified sperm DNA fragmentation, natural conception, assisted-reproduction outcomes, clinical pregnancy, or live birth. Sexual-function findings are mixed and do not establish causality. Evidence on paternal preconception exposure is insufficient, and pregnancy-related label precautions do not by themselves establish risk from paternal exposure. No eligible controlled tirzepatide-specific study assessing semen or clinical fertility outcomes was identified by this search. These therapies should be used for established metabolic indications, not as male infertility treatments. The proposed framework is author-developed, evidence-informed, non-validated, and intended for individualized counseling and prospective evaluation. Full article

(This article belongs to the Special Issue The Latest Research on Male Infertility)

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32 pages, 417 KB

Open AccessReview

Emerging Prognostic Risk Factors in Acute Coronary Syndromes: Beyond Traditional Risk Assessment

by Lorenzo Cangiano, Giancarlo Marenzi, Gianluca Pontone and Nicola Cosentino

J. Clin. Med. 2026, 15(18), 7312; https://doi.org/10.3390/jcm15187312 (registering DOI) - 20 Sep 2026

Abstract

Acute coronary syndromes (ACS) remain a major cause of cardiovascular mortality and long-term morbidity worldwide despite substantial advances in revascularization techniques, antithrombotic therapies, and lipid-lowering strategies. Although contemporary management has significantly improved survival, a considerable residual risk of recurrent ischemic events, adverse ventricular [...] Read more.

Acute coronary syndromes (ACS) remain a major cause of cardiovascular mortality and long-term morbidity worldwide despite substantial advances in revascularization techniques, antithrombotic therapies, and lipid-lowering strategies. Although contemporary management has significantly improved survival, a considerable residual risk of recurrent ischemic events, adverse ventricular remodelling, heart failure, and cardiovascular death persists following ACS. Consequently, accurate risk stratification has become increasingly important to guide individualized secondary prevention and optimize long-term outcomes. Traditional risk assessment after ACS relies largely on clinical characteristics, conventional cardiovascular risk factors, and established risk scores such as GRACE and TIMI. However, growing evidence indicates that several emerging biomarkers and pathophysiological pathways provide additional prognostic information beyond conventional models. These markers reflect distinct biological processes including residual inflammatory activity, myocardial injury and remodelling, renal dysfunction, metabolic impairment, and visceral adiposity. This review summarizes current evidence regarding both established and emerging prognostic markers after ACS across six major pathophysiological domains: lipid abnormalities and traditional cardiovascular risk factors; systemic inflammation and residual inflammatory risk; myocardial injury and adverse ventricular remodelling; cardiorenal dysfunction; visceral adiposity; and anti-inflammatory therapeutic strategies. For each domain, we discuss underlying biological mechanisms, key findings from major clinical trials and registries, and the potential incremental value of biomarkers in contemporary risk stratification. Collectively, these markers support a multidimensional approach to post-ACS risk assessment and may contribute to more personalized therapeutic strategies aimed at reducing residual cardiovascular risk. Full article

(This article belongs to the Special Issue Acute Coronary Syndromes: From Diagnosis to Treatment (2nd Edition))

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9 pages, 4264 KB

Open AccessCase Report

Quantitatively Extreme Sagittal Orientation of the L5-S1 Facet Joints in Adolescent Dysplastic Spondylolisthesis: A Case Report and Mechanistic Considerations

by Yong-Xi Fan, Jia-Yu Fu, Xiao-Ling Luo, Chang-Sheng Liao and Zhong-Jie Zhou

J. Clin. Med. 2026, 15(18), 7311; https://doi.org/10.3390/jcm15187311 (registering DOI) - 20 Sep 2026

Abstract

Background/Objectives: Dysplastic spondylolisthesis is associated with developmental abnormalities of the lumbosacral junction, but the contribution of extremely sagittal L5-S1 facet orientation in an adolescent with an intact pars interarticularis remains incompletely characterized. We aimed to describe this unusual quantitative morphologic phenotype and discuss [...] Read more.

Background/Objectives: Dysplastic spondylolisthesis is associated with developmental abnormalities of the lumbosacral junction, but the contribution of extremely sagittal L5-S1 facet orientation in an adolescent with an intact pars interarticularis remains incompletely characterized. We aimed to describe this unusual quantitative morphologic phenotype and discuss its possible biomechanical implications. Methods: Clinical records and serial imaging of a 14-year-old girl with symptomatic low-grade L5-S1 dysplastic spondylolisthesis were reviewed. Standing radiographs, flexion-extension radiographs, computed tomography (CT), magnetic resonance imaging (MRI), quantitative spinopelvic parameters, intraoperative findings, treatment, and 12-month follow-up were assessed. Results: The patient had approximately one year of progressively worsening low back pain and occasional transient right-leg numbness despite more than 8 months of lumbosacral bracing and more than 6 months of supervised physical therapy. Standing radiographs showed Meyerding grade I L5-S1 anterolisthesis and mild thoracolumbar scoliosis. Quantitative spinopelvic assessment showed a pelvic incidence (PI) of 76.63°, pelvic tilt of 22.21°, sacral slope of 54.42°, lumbar lordosis of 59.5°, sagittal vertical axis of 2.67 cm, and a Dubousset lumbosacral angle of 109°. CT demonstrated an intact pars interarticularis, bilateral facet subluxation, and L5-S1 facet angles of 6° on the left and 3° on the right relative to the sagittal plane. Flexion-extension radiographs showed measurable L5-S1 angular motion from −6.7° to +3.5°, while MRI showed no major central canal stenosis, focal disc herniation, or definite neural compression. Posterior reduction and L5-S1 fusion were performed after individualized counseling, and facet subluxation was confirmed intraoperatively. At 6 and 12 months, the patient remained free of recurrent pain or numbness and radiographs showed maintained lumbosacral alignment. Conclusions: Quantitatively extreme L5-S1 facet sagittalization accompanied by bilateral facet subluxation, an intact pars, and high-PI low-grade spondylolisthesis represents a distinctive morphologic phenotype. This configuration is biomechanically compatible with reduced resistance to anterior shear, although a single case cannot establish independent causality or justify a general indication for early surgery. Comparative quantitative imaging and longitudinal studies are required. Full article

(This article belongs to the Section Orthopedics)

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19 pages, 701 KB

Open AccessArticle

Efficacy of Inelastic Compression Devices with a High Stiffness in Older Breast Cancer Survivors with Moderate and Severe Lymphedema: A Prospective Interventional Study

by Katarzyna Ochałek, Ewelina Matusik and Zbigniew Szygula

J. Clin. Med. 2026, 15(18), 7310; https://doi.org/10.3390/jcm15187310 (registering DOI) - 20 Sep 2026

Abstract

Objectives: The study aimed to assess the effectiveness, physical functioning and comfort of decongestive adjustable compression wraps (ACW, Circaid^® reduction kit), the essential ACW (Circaid^® juxtafit™ essentials) and MLB (Multi-layer bandaging) among patients with breast cancer-related lymphedema (BCRL), divided into a [...] Read more.

Objectives: The study aimed to assess the effectiveness, physical functioning and comfort of decongestive adjustable compression wraps (ACW, Circaid^® reduction kit), the essential ACW (Circaid^® juxtafit™ essentials) and MLB (Multi-layer bandaging) among patients with breast cancer-related lymphedema (BCRL), divided into a moderate (MG, n = 28) and severe group (SG, n = 27), based on BCRL severity. Methods: The treatment lasted 10 days and was carried out over a two-week period. In the first week, all patients were treated by experienced physiotherapists. In the second week, the protocol was continued at home. Measurements, including limb volumes, physical functioning and disease-related symptoms, were performed prior to the intervention (at baseline), as well as following one and two weeks of treatment. Compression comfort was assessed in the groups after one and two weeks. Results: In both groups, a significant reduction in affected limb volume was found after one week (p < 0.001). The pressure under the decongestive ACW device was significantly lower (p < 0.001) in comparison to the essential ACW and MLB. The affected limb joint mobility in the decongestive ACW group was significantly higher after the second week in the SG (p = 0.023). Although minor complications of compression were observed less frequently with MLB than with ACWs, compression comfort was comparable between the groups. Conclusions: Both ACWs may represent feasible alternatives to multi-layer bandaging during the intensive phase of complex decongestive therapy in selected patients. Full article

(This article belongs to the Section Oncology)

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12 pages, 7328 KB

Open AccessArticle

Influence of Anatomical Pelvic Tilt and Anatomical Sacral Slope on Pelvic Orientation and Lumbar Lordosis Distribution in Subjects with High Pelvic Incidence

by Norio Imai, Daisuke Homma, Makoto Shirono, Yuki Endo, Yuki Hirano, Yoji Horigome and Hiroyuki Kawashima

J. Clin. Med. 2026, 15(18), 7309; https://doi.org/10.3390/jcm15187309 (registering DOI) - 20 Sep 2026

Abstract

Background/Objectives: Pelvic incidence (PI) is a key anatomical parameter that influences sagittal spinal alignment and hip–spine mechanics. Anatomically, PI is composed of anatomical pelvic tilt (aPT) and anatomical sacral slope (aSS). However, whether variation in these anatomical components is associated with lumbar lordosis [...] Read more.

Background/Objectives: Pelvic incidence (PI) is a key anatomical parameter that influences sagittal spinal alignment and hip–spine mechanics. Anatomically, PI is composed of anatomical pelvic tilt (aPT) and anatomical sacral slope (aSS). However, whether variation in these anatomical components is associated with lumbar lordosis distribution in subjects with high PI remains unclear. This study aimed to investigate the association between aPT and distal lumbar lordosis distribution in subjects with high PI. Methods: This retrospective cross-sectional study included 320 subjects, of whom 68 had high PI (PI ≥ 60°). Sacral slope (SS), pelvic tilt (PT), anterior pelvic plane angle (APPA), PI, aPT, aSS, thoracic kyphosis (TK), lumbar lordosis (LL), lower arc lordosis (L4–S1 lordosis), and the L4–S1/LL ratio were measured using standing lateral radiographs. In subjects with high PI, associations of aPT as a continuous variable with lower arc lordosis and the L4–S1/LL ratio were evaluated using correlation and multiple linear regression analyses adjusted for age and body mass index (BMI). Results: Sixty-eight subjects (21.3%) met the definition of high PI. Greater aPT was modestly associated with greater lower arc lordosis in unadjusted analysis (Pearson r = 0.258, p = 0.034), whereas the association with the L4–S1/LL ratio did not reach statistical significance (r = 0.219, p = 0.072). After adjustment for age and BMI, the association between aPT and lower arc lordosis was attenuated and did not reach statistical significance (standardized β = 0.217, p = 0.063). The adjusted association between aPT and the L4–S1/LL ratio was also not significant (standardized β = 0.191, p = 0.113). Conclusions: Among subjects with high PI, greater aPT showed a modest positive association with distal lumbar lordosis in unadjusted analysis; however, this association was attenuated after adjustment for age and BMI. These findings suggest that age may partly contribute to variation in distal lumbar lordosis among individuals with high PI and that the anatomical composition of PI should be interpreted with consideration of potential confounding factors. Full article

(This article belongs to the Special Issue Breakthroughs in Spine Biomechanics: Diagnostics and Treatment Approaches for Body Posture, Scoliosis and Chronic Back Pain)

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20 pages, 1457 KB

Open AccessArticle

Association of the Preoperative CALLY Index with Acute Kidney Injury After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Comparison with Other Inflammatory and Immune-Nutritional Indices

by Hatice Şahin, Gülay Ulusal Okyay, Fatma Ayerden Ebinç, Berrak Itır Aylı, Fevzi Coşkun Sökmen, Ferit Aydın, Bülent Aksel and Mehmet Deniz Aylı

J. Clin. Med. 2026, 15(18), 7308; https://doi.org/10.3390/jcm15187308 (registering DOI) - 20 Sep 2026

Abstract

Background/Objectives: Acute kidney injury (AKI) is a frequent complication following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). The association between preoperative inflammatory and immune-nutritional indices and postoperative AKI after CRS-HIPEC remains unclear. We aimed to investigate whether these prespecified candidate preoperative markers are [...] Read more.

Background/Objectives: Acute kidney injury (AKI) is a frequent complication following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). The association between preoperative inflammatory and immune-nutritional indices and postoperative AKI after CRS-HIPEC remains unclear. We aimed to investigate whether these prespecified candidate preoperative markers are associated with postoperative AKI in patients undergoing CRS-HIPEC. Methods: This retrospective single-center study included 87 patients who underwent CRS-HIPEC between October 2022 and April 2025. All received intraoperative cisplatin and mitomycin C. AKI was defined according to Kidney Disease: Improving Global Outcomes serum creatinine criteria. Preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, pan-immune-inflammation value, systemic inflammation response index, and C-reactive protein–albumin–lymphocyte (CALLY) index were calculated from routine laboratory parameters. Each candidate marker was evaluated in a separate model adjusted for age and sex, and then in a second model additionally adjusted for baseline estimated glomerular filtration rate. Discriminatory performance was assessed using receiver operating characteristic analysis. The CALLY index was calculated using albumin in g/dL, lymphocyte count in ×10⁹/L, and C-reactive protein in mg/L. Results: AKI developed in 24 patients (27.6%). In-hospital mortality was higher in patients with AKI than in those without AKI (25.0% vs. 1.6%; p = 0.002). A higher log10-transformed CALLY index remained associated with lower odds of AKI after adjustment for age and sex (adjusted OR, 0.276; 95% CI, 0.113–0.673; p = 0.005). The CALLY index had the numerically highest AUC among the evaluated indices, with moderate discriminatory performance (AUC, 0.708; 95% CI, 0.579–0.836). A data-derived exploratory cutoff of ≤1.640 yielded 79.2% sensitivity and 63.5% specificity. Conclusions: In this selected retrospective cohort of patients without established chronic kidney disease, a lower preoperative CALLY index was associated with postoperative AKI and showed moderate discrimination as an individual marker. The data-derived threshold should be considered exploratory and requires independent validation before clinical application. Full article

(This article belongs to the Section Nephrology & Urology)

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27 pages, 2011 KB

Open AccessReview

Perioperative Fluid Management and Renal Protection in Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC): A Scoping Review

by Gilda Pasta, Camilla L’Acqua, Nicoletta Filetici, Giulia Bernardi, Arturo Cuomo, Edoardo De Robertis, Tiziana Bove, Rachele Simonte and Luciano Frassanito

J. Clin. Med. 2026, 15(18), 7307; https://doi.org/10.3390/jcm15187307 (registering DOI) - 20 Sep 2026

Abstract

Background/Objectives: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a complex, high-risk procedure associated with profound haemodynamic and metabolic perturbations. Perioperative fluid management and the risk of acute kidney injury (AKI) represent two of the most clinically significant and mechanistically interrelated anaesthetic [...] Read more.

Background/Objectives: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a complex, high-risk procedure associated with profound haemodynamic and metabolic perturbations. Perioperative fluid management and the risk of acute kidney injury (AKI) represent two of the most clinically significant and mechanistically interrelated anaesthetic challenges in this setting. This scoping review aimed to synthesise the current evidence on perioperative fluid therapy strategies and renal protection in CRS/HIPEC, examining the pathophysiological rationale, comparative outcomes of different fluid therapy strategies, haemodynamic monitoring modalities, AKI incidence and risk factors, and pharmacological nephroprotective strategies. Methods: The review followed PRISMA guidelines and was registered in the Open Science Framework (osf.io/864pr). Studies specifically addressing fluid management, haemodynamic monitoring, AKI, and nephroprotection in adult patients undergoing CRS/HIPEC were included. Results: Thirty-one studies met inclusion criteria across two thematic domains: 13 addressing fluid therapy (two RCTs, one systematic review, and 10 observational studies) and 18 addressing AKI and renal protection (two RCTs, one systematic review, and 15 observational studies). Liberal intraoperative fluid administration is independently associated with increased morbidity and prolonged hospital stay. Restrictive and goal-directed strategies appear safe and are associated with improved outcomes. AKI incidence ranges from 7.9% to 45.5% depending on chemotherapy regimen, with platin- and taxane-based HIPEC conferring the highest risk. Sodium thiosulfate, amifostine, and cilastatin demonstrate nephroprotective effects in retrospective cohorts; dexmedetomidine shows subclinical renal biomarker benefits in the only RCT identified. Conclusions: The available evidence supports restrictive and goal-directed fluid strategies guided by dynamic haemodynamic monitoring, alongside individualised, cisplatin-dose-adapted nephroprotective protocols. Both fluid overload and renal hypoperfusion represent modifiable risk factors for AKI in CRS/HIPEC. Prospective randomised trials integrating fluid management and renal outcome endpoints are required. Full article

(This article belongs to the Special Issue Clinical Advances in General and Regional Anesthesia)

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18 pages, 14899 KB

Open AccessArticle

Gender Differences Among Urologists in the Assessment and Utilization of ESWL Treatment: Insights from a Multinational Survey of 3747 Participants

by Hajira Karim, Abdullah Hamdullah Azeemi, Duha Yahya, Mona Ayran, Abdallah Mohammad Ibrahim Abu Dayah, Rahaf Salaam, Emad Sibai, Imadeddine Boudjatit, Kani Barzng, Youssef Shalaby, Mehmet Kocak, Guohua Zeng, Valentin Pavlov, M. Pilar Laguna and Jean de la Rosette

J. Clin. Med. 2026, 15(18), 7306; https://doi.org/10.3390/jcm15187306 (registering DOI) - 20 Sep 2026

Abstract

Background/Objectives: This study aimed to examine gender-associated differences in extracorporeal shock-wave lithotripsy (ESWL) utilization as well as urolithiasis diagnostic evaluation, treatment strategy, and follow-up across a multinational sample of urologists and trainees. Methods: A multinational cross-sectional survey of members of the [...] Read more.

Background/Objectives: This study aimed to examine gender-associated differences in extracorporeal shock-wave lithotripsy (ESWL) utilization as well as urolithiasis diagnostic evaluation, treatment strategy, and follow-up across a multinational sample of urologists and trainees. Methods: A multinational cross-sectional survey of members of the Société Internationale d’Urologie (SIU) was conducted from June to July 2022 in seven languages. The survey was completed by 3747 urologists and trainees (283 female and 3464 male respondents) from 108 countries. To reduce baseline differences, propensity-score matching was performed with exact matching on years of clinical practice, continent, and career stage, yielding a matched cohort of 1191 respondents (279 female and 912 male). Categorical comparisons used Cochran–Mantel–Haenszel analyses stratified by a matched-set identifier, and 0–10 scored items were compared using stratified Wilcoxon rank-sum analyses with the matched set as the stratum. Results: In the matched cohort, annual procedural-volume distributions differed by gender for ureterorenoscopy (URS) (p = 0.0009), open surgery (p = 0.002), laparoscopy/robotics (p = 0.010), and percutaneous nephrolithotomy (PCNL) (p = 0.018), whereas ESWL volume did not differ significantly (p = 0.077). Among ESWL-specific categorical practices, coupling-gel use differed by gender (p = 0.029), while alpha-blocker use, antibiotic prophylaxis, JJ-stent use, stone-fragment collection, ESWL-machine type, and operator did not. Among the 851 respondents that completed the 0–10 practice items (186 female, 665 male), urine-culture assessment (8.4 vs. 7.6; p = 0.030), complete blood count (8.0 vs. 7.5; p = 0.047), and repeating ESWL within 7 days (2.5 vs. 3.4; p = 0.048) showed nominal gender-associated differences. The majority of other scored items were similar, including computed tomography (CT) urography (p = 0.055). Because these analyses were exploratory and no multiplicity adjustment was applied, nominally significant findings should be interpreted as hypothesis-generating. Conclusions: In this multinational survey of SIU members, most self-reported ESWL-specific practices were similar between female and male respondents after matching on key demographic, geographic, and professional characteristics. Gender-associated differences were observed in procedural-volume distributions as well as a limited number of reported assessments and procedural items. These findings are exploratory associations rather than causal effects of gender and may reflect measured and unmeasured professional, institutional, geographic, and training-related factors. Full article

(This article belongs to the Special Issue Future-Proof Care for Patients with Kidney Stones)

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12 pages, 4731 KB

Open AccessArticle

Inter- and Intra-Rater Reliability of a Standardized Infrared Thermographic Cellulite Severity Classification System: A Multi-Rater Study

by Patrycja Szczepańska-Ciszewska, Wojciech Michał Glinkowski, Andrzej Śliwczyński, Magdalena Głowacka, Anna Erkiert-Polguj, Agata Kmita, Aleksandra Rybak, Barbara Algiert-Zielińska and Maria Koserczyk

J. Clin. Med. 2026, 15(18), 7305; https://doi.org/10.3390/jcm15187305 (registering DOI) - 20 Sep 2026

Abstract

Background/Objectives: Clinical cellulite grading relies on inspection and palpation and is susceptible to examiner variability. A single experienced assessor previously evaluated a five-grade infrared thermographic classification, but its reproducibility across raters was unknown. To assess inter-rater and intra-rater reliability of a standardized thermographic [...] Read more.

Background/Objectives: Clinical cellulite grading relies on inspection and palpation and is susceptible to examiner variability. A single experienced assessor previously evaluated a five-grade infrared thermographic classification, but its reproducibility across raters was unknown. To assess inter-rater and intra-rater reliability of a standardized thermographic grading workflow applied by trained novice raters. Methods: This secondary reliability study included 78 anterior FLIR P620 scans. Five raters analyzed each scan twice, one week apart, using standardized FLIR Tools settings and a ΔT-based 0–IV scale. The prespecified principal agreement analysis used Gwet’s AC2 with quadratic weights across the full 0–IV scale; a sensitivity analysis recalculated AC2 using only the observed categories. Confidence intervals were estimated by scan-level bootstrap. Results: The scans yielded 780 ratings, all within grades 0–II. Full five-rater exact agreement was 26.9% and 33.3% in rounds 1 and 2, respectively, while within-one-grade agreement was 89.7% and 92.3%. Observed-category AC2, which restricts quadratic weighting to the grades represented in the data (0–II), was 0.786 (95% CI 0.730–0.840) and 0.845 (0.794–0.885). The corresponding prespecified full-scale AC2 values calculated across the theoretical 0–IV weighting range were 0.949 (0.936–0.962) and 0.963 (0.951–0.972). Intra-rater exact agreement ranged from 66.7% to 97.4%, with 100% agreement within one grade for all raters. Conclusions: The workflow demonstrated reproducible ordinal grading within the lower severity categories represented in the dataset, although exact five-rater agreement remained limited. The findings do not establish reliability for grades III–IV, diagnostic accuracy, or clinical utility. Full article

(This article belongs to the Section Dermatology)

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11 pages, 2997 KB

Open AccessArticle

Histopathological Changes in the Uterus, Ovaries, and Fallopian Tubes Following Testosterone Therapy in Transgender Men: A Retrospective Cohort Study from a Tertiary Referral Center

by Kübra Hamzaoğlu Canbolat, Hilal Atılgan Yıldırım, Nil Urgancı, Şennur İlvan, Mahmut Öncül, Koray Gök and Abdullah Tüten

J. Clin. Med. 2026, 15(18), 7304; https://doi.org/10.3390/jcm15187304 (registering DOI) - 20 Sep 2026

Abstract

Background: Gender-affirming testosterone therapy is an essential component of medical transition for transgender men. Despite its widespread use, the histopathological effects of testosterone exposure on the uterus, ovaries, and fallopian tubes remain incompletely characterized. This study aimed to characterize histopathological findings in [...] Read more.

Background: Gender-affirming testosterone therapy is an essential component of medical transition for transgender men. Despite its widespread use, the histopathological effects of testosterone exposure on the uterus, ovaries, and fallopian tubes remain incompletely characterized. This study aimed to characterize histopathological findings in the gynecologic organs of transgender men receiving testosterone therapy before gender-affirming hysterectomy with bilateral salpingo-oophorectomy. Methods: This retrospective cohort study included transgender men who underwent laparoscopic hysterectomy with bilateral salpingo-oophorectomy at a tertiary referral center between 2015 and 2019. Demographic characteristics, duration of testosterone therapy, operative findings, and histopathological results were reviewed. Estrogen receptor (ER) and progesterone receptor (PR) expression in uterine tissues was assessed immunohistochemically. Results: Fifty-two transgender men were included. The median age was 25.5 years (range, 19–46 years), the median body mass index was 24.8 kg/m², and the mean duration of testosterone therapy was 16.1 ± 7.8 months. Proliferative endometrium was the predominant pattern (78.8%), followed by inactive (17.3%) and atrophic (3.8%) endometrium. Endometrial polyps were identified in 13.5% of patients. Multifollicular ovarian morphology was observed in 90.4%, and paratubal cysts in 63.5%. No premalignant or malignant lesions were detected. ER expression was positive in all endometrial samples and in 92% of myometrial specimens, while PR expression was preserved in all evaluated uterine tissues. Conclusions: In this cohort, proliferative endometrium and multifollicular ovarian morphology were common despite testosterone therapy, and uterine ER and PR expression remained detectable. The absence of premalignant or malignant lesions was reassuring within the observed exposure period; however, the retrospective design, modest sample size, absence of a control group, limited characterization of hormone exposure, and lack of longitudinal follow-up preclude conclusions regarding long-term oncologic safety or malignancy risk. Full article

(This article belongs to the Special Issue Advances in Gynecological Diseases (Second Edition))

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19 pages, 1739 KB

Open AccessSystematic Review

Reassessing the Role of Anthracyclines in Early HER2-Positive Breast Cancer in the Era of HER2-Targeted Therapy and Treatment De-Escalation: A Systematic Review and Narrative Synthesis

by Zhuldyz Myrzabay, Nazym Askambayeva, Ahmad J. Harahsheh, Reezal Ishak and Mohamad Aljofan

J. Clin. Med. 2026, 15(18), 7303; https://doi.org/10.3390/jcm15187303 (registering DOI) - 20 Sep 2026

Abstract

Background: Anthracyclines have historically remained a cornerstone of treatment for early HER2-positive breast cancer. However, the emergence of dual HER2 blockade, antibody–drug conjugates, and response-adapted treatment strategies has changed the clinical context in which anthracycline use is considered. Whether anthracyclines continue to provide [...] Read more.

Background: Anthracyclines have historically remained a cornerstone of treatment for early HER2-positive breast cancer. However, the emergence of dual HER2 blockade, antibody–drug conjugates, and response-adapted treatment strategies has changed the clinical context in which anthracycline use is considered. Whether anthracyclines continue to provide sufficient oncologic benefit to justify their additional cardiovascular toxicity remains uncertain. Objectives: This study aims to evaluate the contemporary role of anthracyclines in early HER2-positive breast cancer by synthesizing direct comparative evidence and contextual evidence from prospective de-escalation studies. Design: It involves a systematic review with narrative synthesis. Data Sources and Methods: PubMed, the Web of Science, and CENTRAL were searched for prospective studies published from January 2000 to 31 May 2026. A meta-analysis was initially planned, but only three clinically heterogeneous trials directly compared anthracycline-containing and anthracycline-free regimens. Direct comparative and contextual de-escalation evidence was therefore synthesized separately using a narrative approach. Results: Twelve studies were included. BCIRG-006, TRAIN-2, and TRYPHAENA provided direct comparative evidence; nine additional prospective trials provided contextual evidence on anthracycline-sparing or treatment de-escalation strategies. Direct comparisons generally indicated greater cardiac toxicity with anthracycline-containing regimens, although severe events were uncommon and cardiotoxicity definitions varied. Contextual studies supported the feasibility of contemporary anthracycline-sparing approaches in selected populations but did not provide direct estimates of the effect of anthracycline exposure. Conclusions: Anthracycline-containing regimens appear to confer greater cardiac risk than anthracycline-free regimens, but comparative evidence remains limited. The available evidence supports selective rather than routine anthracycline use, with treatment decisions guided by the anticipated oncologic benefit, cardiovascular risk, tumor characteristics, treatment setting, and patient preferences. Registration: PROSPERO CRD420261296599; registered on 29 January 2026. Full article

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

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12 pages, 1494 KB

Open AccessArticle

A Retrospective Analysis of Inhaled Nitric Oxide and Outcomes in Mechanically Ventilated Patients with COVID-19 ARDS

by Abbie Evans, Shengping Yang, Noella Vinan-Vega, Jose Ramos, Pitchaporn Yingchoncharoen, Jerapas Thongpiya, Arunee Motes, Tarek Shihab, Cesar Peralta, Renee Garcia and Kenneth Nugent

J. Clin. Med. 2026, 15(18), 7302; https://doi.org/10.3390/jcm15187302 (registering DOI) - 20 Sep 2026

Abstract

Background: Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator used as rescue therapy in acute respiratory distress syndrome (ARDS) for transient improvement in oxygenation. Although multiple studies demonstrate improvements in oxygenation parameters, iNO has not consistently shown a mortality benefit or reduced [...] Read more.

Background: Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator used as rescue therapy in acute respiratory distress syndrome (ARDS) for transient improvement in oxygenation. Although multiple studies demonstrate improvements in oxygenation parameters, iNO has not consistently shown a mortality benefit or reduced ventilation duration. Methods: A retrospective cohort study was conducted of mechanically ventilated adults with SARS-CoV-2 (COVID-19) admitted to a medical intensive care unit who received iNO. Demographic characteristics, comorbidities, illness severity scores, timing of iNO initiation, and clinical outcomes were analyzed, with comparisons made between survivors and non-survivors. Results: A total of 94 patients were included. The mean age was 52.0 years (Standard Deviation (SD) 14.1), 70.2% were male, and the mean body mass index was 36.5 kg/m² (SD 10.0). Hypertension (58.5%) and diabetes (36.2%) were the most common comorbidities. The mean Sequential Organ Failure Assessment (SOFA) score was 4.22 (SD 2.79), and the mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 11.69 (SD 6.98). Overall, in-hospital mortality was 85.1% (80/94). The median time from intubation to iNO initiation was 7.6 days (mean 7.7 days). Survivors received iNO significantly earlier than non-survivors (mean 4.14 vs. 8.3 days after intubation, p = 0.024) and had a longer hospital length of stay (mean 37 vs. 23 days, p < 0.01). Duration of iNO therapy did not differ between groups (p = 0.12). Conclusions: In this cohort of critically ill patients with COVID-19 and severe respiratory failure, overall mortality was extremely high. Earlier initiation of inhaled nitric oxide was associated with improved survival, whereas duration of therapy was not. These findings suggest that the timing of iNO administration may be associated with clinical outcomes and warrant further prospective investigation to confirm this association. Full article

(This article belongs to the Section Respiratory Medicine)

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12 pages, 578 KB

Open AccessArticle

Genetic Susceptibility to NSAID-Related Gastrointestinal Adverse Events in Korean Patients: An Exploratory Genome-Wide Association Study

by Jun Hyeob Kim, Jin Yeon Gil, Kyung Hyun Min, Hyun Jeong Kim, Soyoun Yang, Sam Yeol Chang, Byung-Ki Cho, Hyoun Ah Kim, Woorim Kim, Jinhyun Kim, In Ah Choi, Nan Song, Ji Min Han and Kyung Eun Lee

J. Clin. Med. 2026, 15(18), 7301; https://doi.org/10.3390/jcm15187301 (registering DOI) - 20 Sep 2026

Abstract

Background/Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used but can cause clinically significant gastrointestinal adverse events (GI-AEs). However, genetic susceptibility to NSAID-related GI toxicity remains insufficiently characterized in East Asian populations. This exploratory study aimed to identify genetic loci associated with grade [...] Read more.

Background/Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used but can cause clinically significant gastrointestinal adverse events (GI-AEs). However, genetic susceptibility to NSAID-related GI toxicity remains insufficiently characterized in East Asian populations. This exploratory study aimed to identify genetic loci associated with grade ≥ 2 NSAID-related GI-AEs in Korean patients treated with commonly used NSAIDs. Methods: We conducted an exploratory genome-wide association study in a multicenter Korean cohort of NSAID-treated patients recruited from four Korean hospitals. A total of 339 patients were included, comprising 28 cases with grade ≥ 2 GI-AEs and 311 controls without documented GI-AEs. Genotyping was performed using the Korea Biobank Array, followed by imputation and quality control. Genome-wide association analysis was conducted under an additive logistic regression model adjusted for age, sex, and the first two principal components, with additional sensitivity analyses accounting for the specific NSAID type, cumulative DDD, and concomitant medications. Polygenic risk score analysis was performed using summary statistics from an arthritis-treated subset of the KoGES Ansan/Ansung cohort, and the selected variant were further evaluated using multivariable Firth penalized logistic regression. The discriminatory performance of clinical, laboratory, and genetic models was assessed using bootstrap internal validation. Results: The exploratory GWAS identified 20 suggestive variants associated with NSAID-related GI-AEs at p < 1 × 10⁻⁵, although no variant reached genome-wide significance. The KoGES-derived polygenic risk score was significantly associated with GI-AE status in the NSAID cohort, and 10 suggestive variants overlapped with SNPs included in the best-fit PRS model. rs1925245 maintained a consistent association in multivariable Firth penalized logistic regression. Conclusions: These findings suggest that NSAID-related GI-AEs in Korean patients may reflect a multifactorial susceptibility pattern involving both clinical context and polygenic risk. Although exploratory, this study provides candidate genetic signals for future replication and supports the need for larger ancestry-matched pharmacogenomic studies of NSAID-related GI toxicity. Full article

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14 pages, 3721 KB

Open AccessArticle

Nighttime Systolic Blood Pressure and Cardiovascular and All-Cause Mortality in Peritoneal Dialysis Patients: A Single-Center Prospective Cohort Study

by Jing Yu, Jianwen Yu, Rui Yang, Yagui Qiu, Jianbo Li, Xiao Yang, Wei Chen, Xi Xia and Qinghua Liu

J. Clin. Med. 2026, 15(18), 7300; https://doi.org/10.3390/jcm15187300 (registering DOI) - 19 Sep 2026

Abstract

Background/Objectives: The link between ambulatory-blood-pressure-derived measurements and survival outcomes among patients receiving peritoneal dialysis (PD) remains uncertain. This study sought to explore whether nighttime systolic blood pressure (SBP) obtained from 24-h ambulatory blood pressure monitoring (ABPM) is associated with cardiovascular (CV) and all-cause [...] Read more.

Background/Objectives: The link between ambulatory-blood-pressure-derived measurements and survival outcomes among patients receiving peritoneal dialysis (PD) remains uncertain. This study sought to explore whether nighttime systolic blood pressure (SBP) obtained from 24-h ambulatory blood pressure monitoring (ABPM) is associated with cardiovascular (CV) and all-cause mortality in PD individuals. Methods: Between 1 January 2017 and 30 June 2021, this single-center sub-cohort study (derived from a prospective database of PD) enrolled 165 PD participants with a median follow-up of 47.4 months from the date of ABPM completion. Competing risk regression was applied to estimate the association between nighttime SBP and CV mortality, accounting for competing death events. Multivariable Cox proportional hazards regression was utilized to quantify nighttime SBP’s independent correlation with all-cause mortality. Results: Over the follow-up period, 48 patients (29.1%) died, with 28 (58.3%) cases attributed to CV causes. In the fully adjusted model, each 1 SD rise in nighttime SBP corresponded to a subdistribution hazard ratio (SHR) of 1.53 (95% confidence interval [CI], 1.05–2.21; p = 0.026) for CV mortality. In the Cox regression model, every 1 SD increase in nighttime SBP showed an independent association with a 42% excess risk of all-cause mortality (hazard ratio [HR] = 1.42, 95% CI, 1.04–1.93; p = 0.026). Quartile-stratified analyses indicated that participants within the uppermost nighttime SBP quartile exhibited higher mortality risk for both endpoints compared to those in the lowest quartile. Conclusions: Elevated nighttime SBP is associated with increased CV and all-cause mortality risk in PD patients. Full article

(This article belongs to the Section Nephrology & Urology)

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18 pages, 272 KB

Open AccessProtocol

Pain, Emotional Allodynia, and Relational Load (PEARL): Protocol of a Multicenter Observational Case–Control Study Validating the Emotional Allodynia Questionnaire in Fibromyalgia

by Alberto Corriero, Mariateresa Giglio, Alfonso Pilolla, Paolo Trerotoli, Vittorio Schweiger, Enrico Polati, Maria Caterina Pace, Maria Beatrice Passavanti, Gabriele Finco, Salvatore Sardo, Boaz Gedaliahu Samolsky Dekel, Maria Cristina Sorella, Cinzia Di Venosa, Elisabetta Costantino, Daniela De Orsi and Filomena Puntillo

J. Clin. Med. 2026, 15(18), 7299; https://doi.org/10.3390/jcm15187299 (registering DOI) - 19 Sep 2026

Abstract

Background: The International Association for the Study of Pain defines pain as a sensory and an emotional experience, yet no instrument in routine practice quantifies affective hypersensitivity to low-intensity interpersonal stimuli, a pattern we term emotional allodynia, a construct transposed from thermal [...] Read more.

Background: The International Association for the Study of Pain defines pain as a sensory and an emotional experience, yet no instrument in routine practice quantifies affective hypersensitivity to low-intensity interpersonal stimuli, a pattern we term emotional allodynia, a construct transposed from thermal stimuli in major depression, which this study sets out to validate rather than assume. The Emotional Allodynia Questionnaire (AEQ), an 11-item self-report measure, was preliminarily validated in a single-center fibromyalgia sample, showing excellent internal consistency and a unidimensional structure. This protocol describes the multicenter validation phase. Methods: PEARL is a prospective, multicenter, observational case–control study at five Italian tertiary pain centers. Cases are adults with fibromyalgia diagnosed by the 2016 American College of Rheumatology (ACR) criteria; controls are adults with chronic non-cancer pain of defined nociceptive or neuropathic origin. All participants complete the AEQ together with the Central Sensitization Inventory (CSI), Pain Catastrophizing Scale, Beck Depression Inventory-II, State-Trait Anxiety Inventory, Difficulties in Emotion Regulation Scale and a pain visual analog scale, and are reassessed once at 40 ± 10 days. The targets are 274 cases and 151 evaluable controls, sized respectively for the precision of internal consistency within depression strata and for a 95% confidence interval of width 0.10 around an area under the curve of 0.80. Analyses cover internal structure, convergent and discriminant validity, test–retest reliability, AEQ–CSI phenotyping and covariate-adjusted discrimination. Results: Results are not yet available; recruitment began on 10 September 2025 and should be complete by approximately December 2027. Conclusions: The preliminary phase could not say whether the AEQ separates fibromyalgia from other chronic pain, whether the construct holds over time, or whether it survives adjustment for depression, anxiety, catastrophizing and emotion dysregulation. PEARL is designed to test these three questions, and to examine whether the AEQ–CSI phenotypes replicate. Registered on ClinicalTrials.gov (NCT07677631). Full article

(This article belongs to the Section Immunology & Rheumatology)

25 pages, 6036 KB

Open AccessReview

Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

by Carmelo Raffo, Daniele Giacoppo, Davide Capodanno and Antonio Greco

J. Clin. Med. 2026, 15(18), 7298; https://doi.org/10.3390/jcm15187298 (registering DOI) - 19 Sep 2026

Abstract

Antithrombotic therapy management in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remains challenging as it requires simultaneous protection from cardioembolism and coronary ischemic events while minimizing bleeding. The coexistence of these competing risks, along with their different temporal profiles, has [...] Read more.

Antithrombotic therapy management in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remains challenging as it requires simultaneous protection from cardioembolism and coronary ischemic events while minimizing bleeding. The coexistence of these competing risks, along with their different temporal profiles, has driven a major shift in therapeutic strategies over the past decade. Randomized trials have consistently shown that direct oral anticoagulant (DOAC)-based dual antithrombotic therapy (DAT) reduces bleeding as compared with prolonged triple antithrombotic therapy (TAT), supporting early aspirin withdrawal in most patients. At the same time, pooled analyses suggest that this simplification may be accompanied by a small increase in ischemic risk, particularly during the first month after PCI, when the hazard of stent thrombosis is the highest. Contemporary guideline recommendations from Europe and North America are now broadly aligned in favoring a short periprocedural course of TAT followed by DAT with a DOAC and clopidogrel, then transitioning to oral anticoagulant monotherapy. However, important uncertainty remains for patients with very high ischemic or bleeding risk, including those with acute coronary syndromes, complex PCI, prior stent thrombosis, frailty, chronic kidney disease, previous bleeding, or active cancer. In these settings, treatment decisions cannot rely solely on trial-derived estimates or isolated risk scores, but require individualized, dynamic, and phase-specific assessments. This review critically appraises the biologic rationale, randomized evidence, and contemporary guideline recommendations for antithrombotic therapy in patients with AF undergoing PCI, focusing on areas not fully resolved by current guidelines, including modulation strategies, high-risk and underrepresented populations, tailored antithrombotic management, and emerging therapeutic directions. Full article

(This article belongs to the Section Cardiovascular Medicine)

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