Journal of Clinical Medicine

25 pages, 6307 KB

Open AccessReview

Acute Ischemic Stroke in 2026: From Time to Penumbra—An Updated Narrative Review of Reperfusion Strategies with a Latin American Implementation Perspective

by Danilo Alejandro Solarte Ordoñez, Jose Leonel Zambrano Urbano, Harold Enrique Vasquez Ucros, Ana Gabriela Cruz Suarez, Angie Estefanía Arcos Bastidas, Juan David Camacho Bolaños, Darío S. López Delgado, Angela Catalina Vallejo Cajigas, Oriana Rivera-Lozada, Cesar Bonilla Asalde and Joshuan J. Barboza

J. Clin. Med. 2026, 15(16), 6496; https://doi.org/10.3390/jcm15166496 (registering DOI) - 21 Aug 2026

Abstract

Background/Objective: The management of acute ischemic stroke (AIS) has evolved from rigid time-based treatment paradigms toward tissue-based selection guided by advanced neuroimaging, thereby expanding eligibility for reperfusion therapies. To provide an updated narrative review of acute ischemic stroke (AIS) classification and management, with [...] Read more.

Background/Objective: The management of acute ischemic stroke (AIS) has evolved from rigid time-based treatment paradigms toward tissue-based selection guided by advanced neuroimaging, thereby expanding eligibility for reperfusion therapies. To provide an updated narrative review of acute ischemic stroke (AIS) classification and management, with emphasis on extended therapeutic windows for intravenous thrombolysis (IVT) and endovascular therapy (EVT), bridging strategies, posterior circulation stroke, and implementation challenges in Latin America and other resource-constrained settings. Methods: A structured narrative review was conducted using the PubMed/MEDLINE, Embase, Scopus, and LILACS databases, covering the period from 2013 to 2025. Results: Sixty-three studies were selected from 412 records and categorized into etiologic classification, extended-window thrombolysis, EVT and bridging therapy, and posterior circulation stroke. Current evidence supports imaging-guided IVT beyond 4.5 h and EVT up to 24 h in selected patients with salvageable brain tissue, including some individuals with large infarct cores. Recent trials also support EVT for basilar artery occlusion. Tenecteplase offers practical workflow advantages in many centers, particularly where transfer delays and limited access to advanced imaging constrain timely reperfusion decisions. Conclusions: Contemporary AIS management is increasingly guided by pathophysiology and imaging rather than strict time thresholds. However, improving outcomes in middle- and low-income settings requires the implementation of adapted clinical algorithms, strengthening of stroke care networks, and optimization of referral pathways. Full article

(This article belongs to the Special Issue Acute Ischemic Stroke: Current Status and Future Challenges—2nd Edition)

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26 pages, 1341 KB

Open AccessSystematic Review

Association Between Cardiovascular Diseases and Lingual Varices: A Systematic Review and Meta-Analysis

by Aya El Kanfoud-Ezzarraa, Sonia Egido-Moreno, Ani Mantinyan-Hakobyan, Mónica Blázquez Hinarejos, Beatriz González-Navarro, Anna Oliveras Serrano, Eva Otero-Rey and José López-López

J. Clin. Med. 2026, 15(16), 6495; https://doi.org/10.3390/jcm15166495 (registering DOI) - 21 Aug 2026

Abstract

Background/Objectives: Cardiovascular diseases (CVD) remain the leading cause of mortality worldwide. Early identification of individuals at risk is essential to reduce disease burden. Lingual varices (LV), a common oral vascular condition, have been suggested as a potential non-invasive clinical marker of systemic [...] Read more.

Background/Objectives: Cardiovascular diseases (CVD) remain the leading cause of mortality worldwide. Early identification of individuals at risk is essential to reduce disease burden. Lingual varices (LV), a common oral vascular condition, have been suggested as a potential non-invasive clinical marker of systemic vascular alterations. This study aimed to evaluate the association between lingual varices and cardiovascular diseases through a systematic review and meta-analysis. Methods: A systematic review was conducted according to PRISMA guidelines and Cochrane recommendations and registered in PROSPERO (CRD420251172737). Electronic searches were performed in PubMed, Web of Science, and Scopus databases. Observational studies assessing the association between lingual varices and cardiovascular diseases in adults were included. Odds ratios (OR) with 95% confidence intervals (CI) were calculated, and meta-analysis was performed using fixed- or random-effects models depending on heterogeneity. Results: Thirteen studies involving 6322 participants were included. The overall prevalence of lingual varices was 34.8%. The meta-analysis demonstrated a significant association between lingual varices and cardiovascular disease (OR = 4.54; 95% CI: 3.35–6.17). Among the cardiovascular conditions evaluated, hypertension also showed a significant association with lingual varices (OR = 4.14; 95% CI: 1.66–10.29). Lingual varices were also significantly associated with smoking (OR = 3.06; 95% CI: 1.61–5.82) and lower extremity varicose veins (OR = 1.64; 95% CI: 1.04–2.58). No significant association was observed with sex (OR = 0.95; 95% CI: 0.67–1.34; p = 0.77). Conclusions: Lingual varices are significantly associated with cardiovascular disease. Although they may represent a readily identifiable oral finding associated with cardiovascular risk profile, the available evidence does not support their use as an independent screening or diagnostic marker. Further prospective studies are required to determine their predictive value and clinical utility. Full article

(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Oral Mucosal Diseases)

14 pages, 808 KB

Open AccessArticle

Electrophysiological Changes in Children with Isolated Persistent Left Superior Vena Cava: A Case–Control Study

by Sule Arici, Ozlem Surekli Karakus, Gulperi Yagar Keskin, Erkan Tas, Fatih Alparslan Genc, Sezin Bayraktar, Metin Sungur and Ayse Inci Yildirim

J. Clin. Med. 2026, 15(16), 6494; https://doi.org/10.3390/jcm15166494 (registering DOI) - 21 Aug 2026

Abstract

Background: Persistent left superior vena cava (PLSVC) is the most common congenital anomaly of the thoracic venous system and is generally considered a benign variant. This study aimed to evaluate arrhythmia-related electrocardiographic parameters in children with isolated PLSVC and to assess the relationship [...] Read more.

Background: Persistent left superior vena cava (PLSVC) is the most common congenital anomaly of the thoracic venous system and is generally considered a benign variant. This study aimed to evaluate arrhythmia-related electrocardiographic parameters in children with isolated PLSVC and to assess the relationship with coronary sinus dimensions. Methods: This retrospective cross-sectional study included 26 children with isolated PLSVC and 26 age- and sex-matched healthy controls. All participants underwent transthoracic echocardiography and electrocardiographic analysis. Coronary sinus diameters were measured and indexed to body surface area. Electrocardiographic parameters reflecting atrial conduction and ventricular repolarization heterogeneity, including P-wave dispersion, QTc dispersion, Tp–e interval, and indices of cardiac electrophysiological balance (QT/QRS and QTc/QRS), were evaluated. Results: P-wave dispersion (62.15 ± 14.78 vs 35.59 ± 10.02 ms, p < 0.001), QTc dispersion (99.66 ± 30.10 vs. 40.45 ± 10.78 ms, p < 0.001), and Tp–e dispersion (67.29 ± 19.10 vs. 38.42 ± 7.13 ms, p < 0.001) were significantly higher in the PLSVC group. QT/QRS (4.33 ± 0.59 vs. 3.78 ± 0.36, p < 0.001) and QTc/QRS (5.48 ± 0.91 vs. 4.61 ± 0.36, p < 0.001) ratios were also increased. Coronary sinus measurements showed weak and inconsistent correlations with electrocardiographic parameters. Conclusions: Children with isolated PLSVC exhibit significant electrocardiographic alterations reflecting atrial and ventricular electrical heterogeneity. These findings suggest that PLSVC may be associated with subclinical electrophysiological abnormalities beyond a benign anatomical variant. Accordingly, increasing clinical awareness of potential arrhythmic risk during follow-up and considering this aspect in patient evaluation may be appropriate. Full article

(This article belongs to the Special Issue Pediatric Cardiology: Clinical Insights, Diagnostic Advances, and Therapeutic Challenges)

26 pages, 963 KB

Open AccessReview

The Effect of Weight Loss and Metabolic Interventions on Recurrence After Atrial Fibrillation Ablation

by Shihan Fu, Shujie Li, Xiyuan Zhang, Ruoxin Yu and Lin Sun

J. Clin. Med. 2026, 15(16), 6493; https://doi.org/10.3390/jcm15166493 (registering DOI) - 21 Aug 2026

Abstract

Catheter ablation is the cornerstone of rhythm control in atrial fibrillation (AF), yet recurrence remains common, and obesity is among the most consistently implicated modifiable risk factors. Weight reduction and metabolic pharmacotherapy are increasingly used in the periprocedural period, but whether they act [...] Read more.

Catheter ablation is the cornerstone of rhythm control in atrial fibrillation (AF), yet recurrence remains common, and obesity is among the most consistently implicated modifiable risk factors. Weight reduction and metabolic pharmacotherapy are increasingly used in the periprocedural period, but whether they act through a shared pathway has not been systematically examined. This narrative review compares the two approaches and asks whether metabolic agents confer protection beyond weight loss itself. Three observations argue that they do not act identically. First, the benefit of weight reduction is dose-dependent yet contingent on delivery: a structured, physician-led risk-factor program reduced 12-month arrhythmia recurrence (risk ratio 0.53), whereas nurse-led care that improved guideline adherence without structured delivery did not alter the primary endpoint. Second, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been associated with reduced recurrence across BMI strata despite producing only modest weight loss; notably, a randomized trial in patients without cardiovascular or metabolic comorbidity showed no additional benefit, whereas benefit was observed in patients with type 2 diabetes and heart failure. Third, glucagon-like peptide-1 receptor agonists (GLP-1RA) achieve greater weight loss but yield inconsistent recurrence data, and Mendelian randomization suggests their cardiometabolic benefit is largely BMI-mediated, whereas that of SGLT2i is weight-independent. Together, these observations are consistent with a working hypothesis of two partly distinct atrial substrates—an obesity-related substrate responsive to weight reduction, and a metabolic-inflammatory substrate that may respond to SGLT2i predominantly when metabolic comorbidity is present. This framework is hypothesis-generating: it rests on indirect, cross-study comparisons and has not been tested by formal mediation analysis. If confirmed, it would imply that the two interventions are complementary rather than interchangeable. Full article

(This article belongs to the Special Issue Atrial Fibrillation: Contemporary Evidence from Prevention to Catheter Ablation)

22 pages, 911 KB

Open AccessReview

Full-Field Stimulus Threshold: A Key Functional Outcome Measure in Retinal Diseases and Clinical Trials

by Nathan Macha and Minzhong Yu

J. Clin. Med. 2026, 15(16), 6492; https://doi.org/10.3390/jcm15166492 (registering DOI) - 21 Aug 2026

Abstract

Full-field stimulus threshold (FST) testing is a psychophysical method used to assess global retinal function, particularly in patients with severe visual impairment where conventional perimetry is unreliable. This review explores the development, clinical protocols, and applications of FST in retinal diseases, with a [...] Read more.

Full-field stimulus threshold (FST) testing is a psychophysical method used to assess global retinal function, particularly in patients with severe visual impairment where conventional perimetry is unreliable. This review explores the development, clinical protocols, and applications of FST in retinal diseases, with a focus on its role in inherited retinal dystrophies (IRDs) such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). FST has emerged as a key functional outcome measure in clinical trials, particularly in evaluating novel gene therapies for IRDs. Its fixation-independent nature and ability to detect residual visual function make it valuable for assessing disease progression and treatment efficacy. However, challenges remain regarding standardization and test variability. Ongoing efforts seek to standardize and optimize FST protocols and establish it as a standardized metric in both clinical and research settings. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases—Mechanisms, Diagnostics, and Emerging Therapies, 2nd Edition)

11 pages, 565 KB

Open AccessArticle

MRI-Defined Osteonecrosis Extent After Locked Plate Fixation of Proximal Humeral Fractures: Correlation with Shoulder Motion and Radiographic Severity

by Ahmet Serhat Aydin, Dağhan Koyuncu, Alper Şükrü Kendirici, Mert Ballı, Ali Erşen, Görkem Durak and Memduh Dursun

J. Clin. Med. 2026, 15(16), 6491; https://doi.org/10.3390/jcm15166491 - 21 Aug 2026

Abstract

Background/Objectives: Humeral head osteonecrosis is a recognised complication of locked plate fixation for proximal humeral fractures, yet the significance of necrotic lesion extent is poorly characterised. This study quantified MRI-defined osteonecrosis extent and its associations with radiographic severity, shoulder motion, and functional outcomes. [...] Read more.

Background/Objectives: Humeral head osteonecrosis is a recognised complication of locked plate fixation for proximal humeral fractures, yet the significance of necrotic lesion extent is poorly characterised. This study quantified MRI-defined osteonecrosis extent and its associations with radiographic severity, shoulder motion, and functional outcomes. Methods: Twenty-five patients with Neer three- or four-part proximal humeral fractures treated by locked plate fixation between 2010 and 2022 were retrospectively reviewed. Shoulder range of motion, Constant score, American Shoulder and Elbow Surgeons (ASES) score, and visual analogue scale (VAS) pain were assessed. Osteonecrosis severity was graded by the Cruess classification. Necrotic extent was quantified on MRI using an angle-based method on coronal and sagittal images; associations were assessed by simple linear regression among patients with confirmed osteonecrosis (n = 12). Results: At a mean follow-up of 85.4 ± 34.1 months, osteonecrosis was present in 12 of 25 patients (48%). Affected patients had lower shoulder abduction (96.7 ± 27.1° vs. 121.8 ± 29.2°; mean difference −25.1°, 95% CI −47.9 to −2.3; p = 0.031), internal rotation (48.3 ± 15.9° vs. 66.4 ± 15.5°; mean difference −18.1°, 95% CI −32.1 to −4.1; p = 0.014), and external rotation (36.7 ± 16.7° vs. 51.8 ± 26.4°; mean difference −15.1°, 95% CI −29.5 to −0.7; p = 0.041). Functional scores did not differ. Among patients with osteonecrosis (n = 12), greater necrotic angle correlated with higher Cruess stage and reduced abduction (β = −0.141; 95% CI −0.259 to −0.024; p = 0.020). Conclusions: MRI-defined osteonecrosis extent correlates with radiographic severity and reduced shoulder motion after locked plate fixation. Larger necrotic lesions are linked to decreased abduction, with no clear relationship to global functional scores. Quantitative MRI may provide useful information on the structural severity of post-traumatic humeral head osteonecrosis. Full article

(This article belongs to the Special Issue Shoulder and Elbow Diseases: Advances in Diagnosis, Treatment and Rehabilitation)

7 pages, 251 KB

Open AccessCase Report

Otitis Externa in a Newborn After Waterbirth—A Case Report Followed by a Literature Review

by Julia Ufnal, Maria Wolniewicz and Lidia Zawadzka-Głos

J. Clin. Med. 2026, 15(16), 6490; https://doi.org/10.3390/jcm15166490 (registering DOI) - 21 Aug 2026

Abstract

Waterbirth has become a widely adopted alternative to a conventional delivery, with well-documented maternal benefits, but there is an ongoing debate regarding neonatal safety. We would like to report a case of a 10-day-old male neonate who developed acute otitis externa (AOE) following [...] Read more.

Waterbirth has become a widely adopted alternative to a conventional delivery, with well-documented maternal benefits, but there is an ongoing debate regarding neonatal safety. We would like to report a case of a 10-day-old male neonate who developed acute otitis externa (AOE) following waterbirth. Despite the rare occurrence of this disease in children under 2 years of age, prompt diagnosis and timely initiation of appropriate therapy led to a full recovery. This case represents a previously undocumented, yet plausible, complication of waterbirth and underscores the importance of careful neonatal ear assessment and preventive measures in aquatic deliveries. Full article

(This article belongs to the Section Clinical Pediatrics)

17 pages, 2782 KB

Open AccessReview

More than Rehabilitation: The Role of Contextual Factors in Pain Perception and Recovery: What the Physiotherapy Literature Reports—A Narrative Review with a Systematic Search Strategy

by Giulia Leonardi, Francesco Bonanno, Angelo Alito, Francesca Cucinotta, Clara Lombardo, Antonio Di Dio, Francesca Sposito, Carmen Cucinotta, Alfio Garofalo and Simona Portaro

J. Clin. Med. 2026, 15(16), 6489; https://doi.org/10.3390/jcm15166489 - 21 Aug 2026

Abstract

Background: Pain is a multidimensional experience shaped not only by nociceptive input but also by cognitive, emotional, and social processes. In musculoskeletal (MSK) rehabilitation, outcome variability among patients with similar clinical presentations suggests that determinants beyond tissue pathology may influence pain perception [...] Read more.

Background: Pain is a multidimensional experience shaped not only by nociceptive input but also by cognitive, emotional, and social processes. In musculoskeletal (MSK) rehabilitation, outcome variability among patients with similar clinical presentations suggests that determinants beyond tissue pathology may influence pain perception and recovery. Contextual factors (CFs)—communication, therapeutic relationship, patient expectations, and environmental cues—are increasingly recognized yet remain inconsistently integrated into routine practice. Objective: To map how CFs are represented in the physiotherapy literature indexed under that terminology, and to identify where empirical evidence in MSK rehabilitation is present and where it is absent. Methods: A narrative review with a systematic search strategy, reported following SANRA, was conducted in PubMed and Scopus, searched on 31 March 2026. Records were screened against predefined eligibility criteria, including publication from 2006 onwards and English language. Two reviewers independently screened records and resolved disagreements by consensus. Methodological quality was appraised using the Cochrane RoB2 tool for randomized controlled trials and an adapted Newcastle–Ottawa Scale for observational and cross-sectional studies. Conceptual publications were not formally appraised. Each publication was classified as direct clinical evidence (Tier A), indirect mechanistic or implementation-level evidence (Tier B), or conceptual contribution (Tier C). Results: Eight publications were included: no source provided direct clinical evidence in a musculoskeletal rehabilitation population (Tier A), five provided indirect mechanistic or implementation-level evidence (Tier B), and three were conceptual contributions (Tier C). The single randomised controlled trial retrieved was conducted in asymptomatic volunteers and was at high risk of bias for the between-group comparisons of all reported outcomes. Findings are organised as contextual domains, mediating mechanisms, and outcomes. No direct clinical evidence was retrieved; claims regarding expectations, therapeutic alliance, non-verbal communication, and the clinical environment rest on indirect or conceptual sources. Conclusions: CFs may contribute to pain and rehabilitation variability through cognitive, emotional, and relational pathways, complementing rather than replacing evidence-based care. The scarcity of direct clinical evidence within the literature indexed under this terminology is itself a finding. Construct-level searches and pragmatic trials are required to clarify the contribution of individual contextual domains. Full article

(This article belongs to the Special Issue Updates on Physiotherapy in Pain Management)

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21 pages, 1967 KB

Open AccessReview

Reprogramming the Evolution of High-Risk Prostate Cancer: Multidisciplinary Strategies to Delay Castration Resistance

by Younghun Sim, Jae Won Choi, Dong Seob Kim, Jeong Hyun Kim, Sung Goo Yoon and Jung Ki Jo

J. Clin. Med. 2026, 15(16), 6488; https://doi.org/10.3390/jcm15166488 - 21 Aug 2026

Abstract

Background/Objectives: High-risk prostate cancer is a biologically heterogeneous group of tumors carrying a substantial risk of progression to lethal, castration-resistant disease. Although androgen deprivation therapy (ADT) remains the therapeutic backbone, nearly all advanced disease eventually progresses to castration-resistant prostate cancer (CRPC) through [...] Read more.

Background/Objectives: High-risk prostate cancer is a biologically heterogeneous group of tumors carrying a substantial risk of progression to lethal, castration-resistant disease. Although androgen deprivation therapy (ADT) remains the therapeutic backbone, nearly all advanced disease eventually progresses to castration-resistant prostate cancer (CRPC) through Darwinian clonal evolution under sustained therapeutic pressure. This narrative review reframes high-risk prostate cancer management as an effort to reprogram the evolutionary trajectory and delay castration resistance, addressing current risk stratification, androgen receptor (AR)-dependent and AR-independent mechanisms of resistance, and multidisciplinary strategies that modify selective pressure. Methods: A narrative review of the literature was conducted, including peer-reviewed studies, pivotal phase III trial reports, and current clinical practice guidelines indexed in PubMed, Scopus, and Web of Science up to 2026. Sources on high-risk and castration-resistant prostate cancer, the biology of treatment resistance, and multidisciplinary treatment intensification were selected and synthesized. Results: Treatment intensification has been extended to high-risk biochemical recurrence (EMBARK), directed by biomarkers in PTEN-deficient disease (CAPItello-281), and moved earlier through prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PSMAfore, PSMAddition). In localized disease, effective AR-pathway intensification with abiraterone (STAMPEDE) contrasts with the failure of chemotherapy (PEACE-2) and enzalutamide (ENZARAD). Emerging therapies targeting lineage plasticity exploit its dynamic and potentially reversible biology, raising the prospect of reversing established resistance rather than merely delaying it. CAPItello-281 and PSMAddition have immature overall survival data and are not yet standard of care. Conclusions: Coordinated multidisciplinary care, matched to the disease stage and molecular context, offers a realistic path to delay castration resistance and improve survival. Full article

(This article belongs to the Special Issue Delaying the Progression to Castration Resistance: Integrating Multidisciplinary Strategies and Tumor Survival Mechanisms in High-Risk Prostate Cancer)

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27 pages, 2653 KB

Open AccessArticle

Explainable Multimodal Machine Learning Predicts 90-Day Treatment Failure in Older Patients with Fragility Fractures of the Pelvis

by Kangwei Wang, Yulin Cao, Nan Gao, Cong Ma, Jianwen Wang, Zishen Xia, Aiwen Gui, Yong Liu and Yuxiong Weng

J. Clin. Med. 2026, 15(16), 6487; https://doi.org/10.3390/jcm15166487 - 21 Aug 2026

Abstract

Background: Fragility fractures of the pelvis (FFP) are increasingly encountered in older adults, yet early deterioration is difficult to anticipate because fracture instability interacts with frailty and systemic vulnerability. We developed and validated an admission-based multimodal framework to predict 90-day treatment failure [...] Read more.

Background: Fragility fractures of the pelvis (FFP) are increasingly encountered in older adults, yet early deterioration is difficult to anticipate because fracture instability interacts with frailty and systemic vulnerability. We developed and validated an admission-based multimodal framework to predict 90-day treatment failure (TF90) before definitive management. Methods: This multicentre retrospective prediction study included 1684 consecutive patients aged ≥65 years with FFP treated at five tertiary hospitals. TF90 was defined as persistent fracture-related pain or immobility, delayed conversion to operative stabilisation, secondary displacement, FFP-related unplanned readmission, revision or unplanned reoperation, or all-cause mortality within 90 days. Only predictors available within 24 h of admission and before the definitive treatment decision were eligible, including CT-defined fracture morphology, frailty, clinical characteristics and routine laboratory biomarkers; DXA and specialised bone metabolism measurements were evaluated separately in an extended model. Four prespecified models were developed in 985 patients, temporally validated in 520 patients and evaluated in a completely held-out Centre E internal–external validation cohort of 179 patients, with additional leave-one-centre-out internal–external cross-validation. Results: TF90 occurred in 307 patients (18.2%) and increased from 8.1% in FFP I to 37.1% in FFP IV. Higher risk was associated with advanced age, greater frailty, impaired prefracture mobility, bilateral posterior ring injury, greater displacement, systemic inflammation, hypoalbuminaemia and renal dysfunction. In temporal validation, AUROCs were 0.732 for the simple logistic model, 0.763 for the core logistic model, 0.759 for the core random forest and 0.755 for the extended random forest. Neither greater algorithmic complexity nor specialised skeletal measurements provided reproducible incremental value. A development-derived high-risk stratum had a TF90 incidence of 32.2% and contained 70.0% of all events. At the fixed threshold of 0.209, sensitivity was 71.3%, specificity 70.0% and negative predictive value 93.1%. Conclusions: Pretreatment integration of pelvic ring mechanics, frailty and routinely available systemic biomarkers enables clinically relevant enrichment of older patients at risk of TF90. The model is best positioned to support intensified surveillance and structured reassessment rather than determine operative treatment. Independent prospective external validation, recalibration and clinical impact evaluation are required before routine implementation. Full article

(This article belongs to the Special Issue Clinical Applications of Artificial Intelligence and Machine Learning in Diagnosis and Therapy)

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14 pages, 654 KB

Open AccessArticle

Association Between Adherence to a Locally Adapted Enhanced Recovery After Surgery Pathway and Perioperative Outcomes After Open Abdominal Aortic Aneurysm Repair: A Retrospective Cohort Study

by Zhiyi Yang, Qinghe Wang, Qingfeng Li, Xinyu Cheng, Yutong Liu, Jing Cai and Tong Qiao

J. Clin. Med. 2026, 15(16), 6486; https://doi.org/10.3390/jcm15166486 - 21 Aug 2026

Abstract

Objective: Open surgical repair (OSR) remains an important treatment for abdominal aortic aneurysm (AAA), but its invasiveness contributes to substantial perioperative risk. Although Enhanced Recovery After Surgery (ERAS) pathways have improved outcomes across several surgical specialties, evidence supporting their use in open aortic [...] Read more.

Objective: Open surgical repair (OSR) remains an important treatment for abdominal aortic aneurysm (AAA), but its invasiveness contributes to substantial perioperative risk. Although Enhanced Recovery After Surgery (ERAS) pathways have improved outcomes across several surgical specialties, evidence supporting their use in open aortic surgery, particularly in Chinese clinical settings, remains limited. We, therefore, evaluated the association between adherence to a locally adapted ERAS pathway and early perioperative outcomes after elective OSR for AAA. Methods: This single-center retrospective cohort study included 182 patients who underwent elective OSR for AAA. Patients who received at least 70% of the 30 ERAS elements were assigned to the ERAS group (n = 93), whereas those who received less than 70% were assigned to the control group (n = 89). A total of 152 patients remained after 1:1 matching of the two groups using propensity score. Quantile regression and logistic regression models were used to evaluate the impact of the ERAS protocol on postoperative length of stay, 30-day mortality, ICU admission rate, hospital cost, major complications, and readmission. Results: After matching, baseline and aneurysm characteristics were generally comparable between groups. The ERAS group demonstrated a significantly reduced risk of major complications (OR = 0.33; 95% CI 0.16–0.71; p = 0.004) and postoperative nausea and vomiting (OR = 0.10; 95% CI 0.01–0.80; p = 0.030). The time to postoperative bowel movement was 1 day earlier in the ERAS group (p < 0.001). The incidence of postoperative cardiac complications was significantly lower in the ERAS group (2.6% vs. 11.8%; p = 0.028). Pulmonary complications were also markedly reduced in the ERAS group (1.3% vs. 19.7%; p < 0.001). The ERAS group was associated with a reduction in postoperative length of hospital stay by 2 days (p < 0.001) and a decrease in hospital cost by 8065 RMB (p < 0.001). Conclusions: Higher adherence to a locally adapted ERAS pathway was associated with fewer major complications, faster bowel recovery, shorter postoperative hospitalization, and lower hospital costs after elective open AAA repair. These findings support prospective multicenter evaluation and further context-specific implementation of ERAS in open aortic surgery. Full article

(This article belongs to the Special Issue Aortic Diseases: Modern Strategies in Diagnosis, Management, and Prevention of Complications)

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19 pages, 1800 KB

Open AccessReview

Resin Infiltration in the Conservative Management of Incipient Dental Caries: An Evidence-Based Review

by Gildo C. Santos, Jr. and Maria Jacinta M. C. Santos

J. Clin. Med. 2026, 15(16), 6485; https://doi.org/10.3390/jcm15166485 - 21 Aug 2026

Abstract

Dental caries is a biofilm-mediated, non-communicable, multifactorial disease in which the balance between demineralization and remineralization determines whether an initial enamel lesion remains stable, arrests, or progresses toward cavitation. Contemporary caries management prioritizes preservation of tooth structure and emphasizes individualized decisions based on [...] Read more.

Dental caries is a biofilm-mediated, non-communicable, multifactorial disease in which the balance between demineralization and remineralization determines whether an initial enamel lesion remains stable, arrests, or progresses toward cavitation. Contemporary caries management prioritizes preservation of tooth structure and emphasizes individualized decisions based on lesion activity, cavitation status, cleansability, radiographic depth, and patient’s caries risk. Resin infiltration has emerged as a microinvasive approach positioned between noninvasive preventive strategies and conventional restorative treatment. This evidence-based narrative review summarizes the current literature on resin infiltration for incipient, non-cavitated proximal carious lesions in permanent teeth, with emphasis on diagnosis, case selection, clinical protocol, and current evidence. A structured search of three databases (PubMed, Embase, and the Cochrane Central Register of Controlled Trials) identified randomized clinical trials, observational clinical studies, systematic reviews, narrative reviews, and relevant in vitro investigations. The strongest clinical evidence supports resin infiltration for non-cavitated proximal lesions in permanent teeth, particularly enamel and selected outer dentin lesions, where long-term studies demonstrate reduced radiographic progression. In vitro studies indicate that lesion penetration, enamel hardness, and surface roughness depend on lesion characteristics, pretreatment, and technique, and help explain the caries-arresting effect. Current evidence shows that resin infiltration should be considered a selective microinvasive option for incipient proximal caries, guided by lesion assessment and patient’s caries risk rather than a universal substitute for prevention or restoration. Full article

(This article belongs to the Special Issue Oral Health and Systemic Diseases: Clinical Insights)

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19 pages, 7497 KB

Open AccessArticle

Association Between Preoperative Cerebrovascular High-Risk Status and Long-Term Ischemic Stroke After EVAR

by Linyao Zhu, Chengxin Weng, Jichun Zhao, Bin Huang, Ding Yuan, Tiehao Wang, Jinting Ge, Huawei Zhang and Jiarong Wang

J. Clin. Med. 2026, 15(16), 6484; https://doi.org/10.3390/jcm15166484 - 21 Aug 2026

Abstract

Objective: To investigate the impact of asymptomatic high-risk status for ischemic stroke on patients with abdominal aortic aneurysm undergoing endovascular aortic repair (EVAR). Methods: Eligible patients with abdominal aortic aneurysm who underwent EVAR between January 2011 and December 2021 were enrolled in this [...] Read more.

Objective: To investigate the impact of asymptomatic high-risk status for ischemic stroke on patients with abdominal aortic aneurysm undergoing endovascular aortic repair (EVAR). Methods: Eligible patients with abdominal aortic aneurysm who underwent EVAR between January 2011 and December 2021 were enrolled in this retrospective cohort study. Propensity score matching (PSM) was used to balance baseline characteristics between the cerebrovascular high-risk group and the standard control group. The impact of cerebrovascular high-risk status on short- and long-term outcomes was assessed using Cox proportional hazards regression and generalized linear models, with results presented as hazard ratios (HRs), odds ratios (ORs), and corresponding 95% confidence intervals (CIs). Results: A total of 1080 patients were included (299 high-risk, 781 standard). During the 13-year follow-up period, ischemic stroke occurred in 45 patients (15.1%) in the high-risk group (HR, 7.01; 95% CI, 4.11–11.94; p < 0.001). The high-risk group also had a higher incidence of major adverse cardiovascular and cerebrovascular events (MACCEs), which occurred in 129 patients (43.1%) (HR, 1.78; 95% CI, 1.43–2.24; p < 0.001). These findings remained consistent across inverse probability of treatment weighting (IPTW) and propensity score matching combined with multivariable generalized linear model (PSM+MVA-GLM) analyses. Conclusions: Although no significant increase in perioperative cerebrovascular adverse events was observed in asymptomatic patients with a preoperative cerebrovascular high-risk status, their worse long-term prognosis appears to be associated with this risk status. This association highlights the need for rigorous cardiovascular and cerebrovascular risk management in this vulnerable population after surgery. Full article

(This article belongs to the Section Vascular Medicine)

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16 pages, 1410 KB

Open AccessSystematic Review

Comparison of Perioperative, Oncologic, and Functional Outcomes Following Robotic and Laparoscopic Intersphincteric Resection for Low Rectal Cancer: A Systematic Review and Meta-Analysis

by Konstantinos Kossenas, Maximos Frountzas, Athanasios Syllaios, Nikolaos Pararas, Panagiotis Kokoropoulos, Dimosthenis Michelakis, Konstantinos Tsimogiannis, Dimitrios Symeonidis and Dimitrios Schizas

J. Clin. Med. 2026, 15(16), 6483; https://doi.org/10.3390/jcm15166483 - 21 Aug 2026

Abstract

Background: Intersphincteric resection (ISR) is a technically demanding sphincter-preserving procedure for low rectal cancer. While robotic surgery may offer technical advantages, evidence comparing robotic ISR (R-ISR) and laparoscopic ISR (L-ISR) remains limited. This study aimed to compare perioperative, oncologic, and functional outcomes [...] Read more.

Background: Intersphincteric resection (ISR) is a technically demanding sphincter-preserving procedure for low rectal cancer. While robotic surgery may offer technical advantages, evidence comparing robotic ISR (R-ISR) and laparoscopic ISR (L-ISR) remains limited. This study aimed to compare perioperative, oncologic, and functional outcomes between R-ISR and L-ISR. Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA 2020. PubMed, Scopus, and Cochrane Library were searched up to 1 March 2026. Comparative studies evaluating R-ISR versus L-ISR in adult patients with low rectal cancer were included. Random-effects models were used to calculate mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I². Subgroup and sensitivity analyses were performed. Results: Seven studies were included. R-ISR was associated with a significantly longer operative duration (MD 34.53 min, 95% CI 7.48 to 61.59; p = 0.02; I² = 81%), a lower rate of overall complications (OR 0.78, 95% CI 0.61 to 0.99; p = 0.04; I² = 0%), a statistically lower Wexner score at 12 months, although the magnitude of the difference was small and its clinical significance uncertain (MD −1.53, 95% CI −2.54 to −0.51; p = 0.02; I² = 0%), and a slightly lower lymph node yield (MD −1.06, 95% CI −2.05 to −0.08; p = 0.04; I² = 65%). No significant differences were observed in blood loss (MD −8.15, 95% CI −23.03 to 6.73; p = 0.20; I² = 37%), conversion to open surgery (OR 0.35, 95% CI 0.02 to 6.02; p = 0.13; I² = 0%), anastomotic leakage (OR 0.92, 95% CI 0.61 to 1.37; p = 0.60; I² = 0%), length of hospital stay (MD −0.48, 95% CI −1.16 to 0.21; p = 0.12; I² = 0%), and CRM positivity (OR 0.93, 95% CI 0.01 to 69.04; p = 0.87; I² = 0%). Subgroup analyses in experienced surgeons and high-volume centers demonstrated no statistically significant differences across outcomes. Sensitivity analyses showed that several results were not robust. Conclusions: Evidence to date does not show superiority of robotic or laparoscopic ISR. Robotic ISR was associated with longer operative time and lower overall complication rates but most perioperative and oncologic outcomes were comparable. After robotic ISR, the 12-month Wexner scores were statistically lower, although the magnitude of this difference was small and the clinical significance uncertain. These results should be interpreted with caution given the limited non-randomized evidence base. PROSPERO Registration: CRD420261359130. Full article

(This article belongs to the Special Issue Clinical Advancements in Laparoscopic Surgery for Gastrointestinal Diseases)

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11 pages, 1224 KB

Open AccessArticle

Comparison of Two Surgical Techniques for Implantation of the Ponto^® Bone Conduction Implant

by Paulina Podlawska-Nowak, Wojciech Gawęcki and Anna Bartochowska

J. Clin. Med. 2026, 15(16), 6482; https://doi.org/10.3390/jcm15166482 - 21 Aug 2026

Abstract

Objectives: The aim of this study was to compare the surgical and postoperative clinical outcomes of punch-only and linear incision techniques for implantation of the Ponto^® bone conduction implant. Methods: Surgical and follow-up data were collected from 101 patients: 46 [...] Read more.

Objectives: The aim of this study was to compare the surgical and postoperative clinical outcomes of punch-only and linear incision techniques for implantation of the Ponto^® bone conduction implant. Methods: Surgical and follow-up data were collected from 101 patients: 46 treated with Minimally Invasive Ponto^® Surgery (MIPS) and 55 with the linear incision technique (LT). The analysis focused on: (1) the surgical procedure, including operative time and intraoperative complications; (2) the healing process; and (3) long-term implant-site outcomes, including implant loss. Results: Median operative time was significantly shorter for MIPS than for LT (30 min vs. 40 min, p < 0.001). No major intraoperative complications were observed in either group. Adverse skin reactions were more frequent in the LT group than in the MIPS group (18.2% vs. 8.7%), but the difference was not statistically significant (p = 0.249). A single implant loss occurred in the LT group 18 months after surgery and was unrelated to failed osseointegration or the surgical technique, being caused by recurrent cholesteatoma. Conclusions: MIPS was associated with a significantly shorter operative time than the LT. Both MIPS and LT appear to be safe techniques. No statistically significant differences were detected between the groups with respect to adverse skin reactions or implant survival during the follow-up period. Full article

(This article belongs to the Special Issue Clinical Advances in Hearing Loss: Diagnosis, Treatment, and Management)

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12 pages, 1251 KB

Open AccessArticle

Neutropenia and Lymphopenia in Systemic Lupus Erythematosus: Distinct Phenotypes and Associated Factors in a Saudi Multicenter Study

by Roaa Aljohani, Ghada Aljanobi, Khawla K. Alghanim, Nadeem Butt, Alaa Ahmed, Farah Alabbasi and Samar Alharbi

J. Clin. Med. 2026, 15(16), 6481; https://doi.org/10.3390/jcm15166481 - 21 Aug 2026

Abstract

Background/Objectives: Neutropenia and lymphopenia are common hematologic manifestations of systemic lupus erythematosus (SLE), but whether they represent distinct phenotypes is not well established. This study evaluated their prevalence, patterns, and associated factors. Methods: This multicenter retrospective study included 353 adults with [...] Read more.

Background/Objectives: Neutropenia and lymphopenia are common hematologic manifestations of systemic lupus erythematosus (SLE), but whether they represent distinct phenotypes is not well established. This study evaluated their prevalence, patterns, and associated factors. Methods: This multicenter retrospective study included 353 adults with SLE from three Saudi centers. Cytopenias were defined using prespecified laboratory criteria. Patients were classified as having neither abnormality, isolated neutropenia, isolated lymphopenia, or both. Multivariable logistic regression was used to assess factors associated with ever-neutropenia and ever-lymphopenia. Results: Leukopenia occurred in 141 patients (39.9%). Ever-neutropenia and ever-lymphopenia were each observed in 88 patients (24.9%); 47 (13.3%) had isolated neutropenia, 47 (13.3%) had isolated lymphopenia, and 41 (11.6%) had both abnormalities. Persistent neutropenia and lymphopenia occurred in 22 (6.2%) and 23 (6.5%) patients, respectively. Most neutropenia was mild, and only three patients had severe neutropenia. The four phenotypes differed in age, body mass index, autoimmune hemolytic anemia, platelet count, anti-Smith positivity, and immunosuppressive exposure. No included variable was independently associated with ever-neutropenia. Ever-lymphopenia was independently associated with male sex (aOR 2.66, 95% CI 1.22–5.81), anti-Smith positivity (aOR 2.71, 95% CI 1.40–5.24), and exposure to azathioprine (aOR 2.07, 95% CI 1.16–3.71), mycophenolate mofetil use (aOR 2.79, 95% CI 1.42–5.52), and rituximab use (aOR 3.83, 95% CI 1.50–9.75). Conclusions: Neutropenia and lymphopenia each occurred in one-quarter of patients with SLE, whereas persistent cytopenias were uncommon. No independent associations were identified for ever-neutropenia. The demographic, serologic, and treatment-related associations of ever-lymphopenia support separate evaluation of the two abnormalities in SLE. Full article

(This article belongs to the Section Immunology & Rheumatology)

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33 pages, 11097 KB

Open AccessReview

Structural and Functional Treatment of Persistent Spinal Pain Syndrome Type 2: A Fibrosis-Stratified Network Meta-Analysis of Epidural Adhesiolysis and Neuromodulation

by Wolfgang Auffermann, Mohammed Al Jumaily and Alina Auffermann

J. Clin. Med. 2026, 15(16), 6480; https://doi.org/10.3390/jcm15166480 - 21 Aug 2026

Abstract

Background/Objectives: Persistent spinal pain syndrome type 2 (PSPS-T2) is treated with two mechanistically distinct interventional families: epidural adhesiolysis (EA), directed at structural epidural pathology, and neuromodulation (NM), directed at modulation of nociceptive signaling. Epidural fibrosis is a biologically plausible candidate for treatment [...] Read more.

Background/Objectives: Persistent spinal pain syndrome type 2 (PSPS-T2) is treated with two mechanistically distinct interventional families: epidural adhesiolysis (EA), directed at structural epidural pathology, and neuromodulation (NM), directed at modulation of nociceptive signaling. Epidural fibrosis is a biologically plausible candidate for treatment stratification, but whether it independently modifies treatment response remains unproven. This study reviewed the available evidence to determine both the comparative findings and the limitations imposed by the current evidence architecture. Methods: A PROSPERO-registered systematic review and frequentist random-effects network meta-analysis were performed. Studies were classified at the study level, rather than the individual-patient level, as fibrosis-positive (structurally confirmed) or unselected (without confirmed fibrosis). Treatment effects were synthesized separately within each stratum, and an exploratory study-level meta-regression evaluated fibrosis status as a potential moderator. Results: The final dataset comprised 87 studies including 33,504 patients: 40 fibrosis-positive studies (n = 4180) and 47 fibrosis-unselected studies (n = 29,324). Treatment family and fibrosis status were almost completely confounded. EA was evaluated almost exclusively in fibrosis-positive cohorts, whereas NM was evaluated almost exclusively in fibrosis-unselected studies. Although pooled improvements in pain (−0.97 vs. −0.63) and disability (−11.01 vs. −8.46) were greater in fibrosis-positive studies, these differences cannot be attributed independently to fibrosis. Residual heterogeneity remained substantial (I² 71–92%). Peripheral nerve field stimulation and EA protocols incorporating steroid, hyaluronidase, and hypertonic saline achieved the highest probability score for pain relief. All probability scores for the treatments should be interpreted as exploratory. Conclusions: Discordance between EA and NM in PSPS-T2 stems from structurally different populations, precluding pooled comparative classifications or claims that fibrosis modifies treatment effect. While fibrosis remains a promising candidate stratifier, proving it requires prospective trials that stratify randomization to EA versus NM following standardized fibrosis assessment. Full article

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

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18 pages, 1325 KB

Open AccessFeature PaperArticle

Risk Factors for Proximal Junctional Kyphosis in Osteoporotic Versus Non-Osteoporotic Patients After Adult Spinal Deformity Surgery

by Tae Soo Shin, Jin-Sung Park, Dong-Ho Kang, Jun-Seok Oh and Se-Jun Park

J. Clin. Med. 2026, 15(16), 6479; https://doi.org/10.3390/jcm15166479 - 21 Aug 2026

Abstract

Background/Objectives: Proximal junctional kyphosis (PJK) is a frequent mechanical complication following adult spinal deformity (ASD) surgery, and osteoporosis is a well-recognized risk factor. However, whether the underlying risk factor profiles for PJK differ according to bone mineral density status remains unclear. This [...] Read more.

Background/Objectives: Proximal junctional kyphosis (PJK) is a frequent mechanical complication following adult spinal deformity (ASD) surgery, and osteoporosis is a well-recognized risk factor. However, whether the underlying risk factor profiles for PJK differ according to bone mineral density status remains unclear. This study aimed to identify and compare independent risk factors for PJK between osteoporotic and non-osteoporotic patients following long-segment posterior spinal fusion for ASD. Methods: This retrospective cohort study included 356 patients who underwent ≥5-level posterior fusion to the sacrum or pelvis for ASD with a 2-year follow-up. Patients were stratified into a non-osteoporotic (non-OP; n = 284) and an osteoporotic (OP; n = 72) group based on preoperative dual-energy X-ray absorptiometry (T-score ≤ −2.5). PJK was defined as a proximal junctional angle (PJA) ≥20° with an increase of ≥10° from the preoperative value. Demographic, surgical, and radiographic variables were analyzed separately for each group using univariate and stepwise multivariate logistic regression analyses. Predictive performance was assessed using receiver operating characteristic curve analysis. Results: The overall PJK incidence tended to be higher in the OP group than the non-OP group (36.1% vs. 24.6%, p = 0.055), and fracture-type PJK occurred significantly more frequently in osteoporotic patients (29.2% vs. 15.8%, p = 0.016). The variables that reached statistical significance differed between the two groups. In the non-OP group, lower Hounsfield units at the upper instrumented vertebra (UIV; OR = 0.990, p = 0.011), higher preoperative PJA (OR = 1.098, p < 0.001), and greater L1 pelvic angle (L1PA) offset indicating relative overcorrection (OR = 1.136, p < 0.001) were independent predictors of PJK. In the OP group, higher preoperative PJA (OR = 1.149, p = 0.007) and greater age-adjusted pelvic incidence–lumbar lordosis offset (OR = 1.052, p = 0.039) were identified as independent risk factors. Multivariable models demonstrated acceptable discriminative ability in both groups (area under the curve [AUC] = 0.741, 95% confidence interval [CI] = 0.671–0.804 for the non-OP group; AUC = 0.753, 95% CI = 0.632–0.867 for the OP group; optimism-corrected AUC 0.729 and 0.735 after bootstrap internal validation). Conclusions: The variables associated with PJK differed according to osteoporosis status following ASD surgery. Careful UIV selection avoiding kyphotic junctional alignment may be relevant for both groups. Avoiding overcorrection relative to the age-adjusted target may warrant particular attention in osteoporotic patients, while UIV bone quality and L1PA overcorrection may be relevant to surgical planning in non-osteoporotic patients. Full article

(This article belongs to the Special Issue Advances in Spinal Deformity: Current Challenges and Future Directions)

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14 pages, 2596 KB

Open AccessArticle

Artificial Intelligence-Assisted Analysis of Retinal Pigment Epithelium Tears in Patients with Neovascular Age-Related Macular Degeneration Treated with Aflibercept (2 mg and 8 mg) and Faricimab: A Single-Centre Retrospective Case Series

by Veronika Eggarter, Ludovico Ruscitti, Niccolò Ascioti, Matteo Bonanata, Arianna Peyla, Filippo Simona, Moreno Menghini and Gabriela Grimaldi

J. Clin. Med. 2026, 15(16), 6478; https://doi.org/10.3390/jcm15166478 - 21 Aug 2026

Abstract

Purpose: We aimed to describe retinal pigment epithelium (RPE) tears in patients with neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED), focusing on OCT features and AI-assisted image analysis. Methods: This retrospective case series included patients with neovascular AMD [...] Read more.

Purpose: We aimed to describe retinal pigment epithelium (RPE) tears in patients with neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED), focusing on OCT features and AI-assisted image analysis. Methods: This retrospective case series included patients with neovascular AMD and PED who developed RPE tears between 2020 and 2025 after treatment with intravitreal aflibercept (2 mg or 8 mg) or faricimab. Multimodal imaging, including spectral-domain OCT and infrared imaging, was reviewed. PED morphology, fluid characteristics, RPE denudation, timing of RPE tear, and visual outcomes were analyzed using manual grading and AI-assisted software. Results: Among 375 PED-bearing eyes, 11 eyes of 11 patients developed an RPE tear (2.9%), of which 10 (90.9%) were temporally associated with anti-VEGF treatment. Rates were similar across agents—2.7% (aflibercept 2 mg), 3.0% (aflibercept 8 mg) and 2.4% (faricimab)—with no significant difference. Eight eyes (72.7%) were treatment-naïve and one tear (9.1%) occurred spontaneously after hemorrhage without recent injection. Among treatment-associated tears, 30% followed the first and 50% the second injection (mean 2.1 injections), detected a mean of 44 ± 30 days after the last injection. Mean baseline PED height was 594.8 ± 239.2 μm and median AI-derived PED volume was 2922 nL. Mean RPE-denudation area at detection was 5.25 ± 3.87 mm², remaining stable in 7 of 9 evaluable eyes. Visual acuity was stable or improved in seven eyes; four lost ≥15 ETDRS letters. Conclusions: RPE tears were an uncommon, predominantly early complication occurring in eyes with large PEDs, with no excess risk from second-generation agents. AI-assisted OCT may aid anatomical characterisation, and most eyes retained vision with continued therapy. Full article

(This article belongs to the Special Issue Imaging and Molecular Biomarkers: The New Approach to Degenerative Retinal Diseases)

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