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BACKGROUND: Surgical management of Crohn’s disease of the colon and rectum frequently requires total proctocolectomy with end ileostomy. There are limited data on the need for Crohn’s disease–directed therapy and the prevalence of recurrence after surgery. OBJECTIVE: To determine the risk of small-bowel Crohn’s disease recurrence and evaluate risk factors for postoperative recurrence after total proctocolectomy with end ileostomy. DESIGN: Retrospective cohort study. SETTINGS: Multistate tertiary health care system. PATIENTS: Adult patients with Crohn’s disease undergoing total proctocolectomy with end ileostomy between 2014 and 2023. MAIN OUTCOME MEASURES: The primary outcome was small-bowel Crohn’s disease recurrence. RESULTS: A total of 193 patients with a median age of 45 years (interquartile range, 34–61) were included. More than half of the patients (n = 102; 52.9%) had a history of small-bowel Crohn’s disease, and the majority (n = 134; 69.4%) received biologic therapy before surgery. The median follow-up time was 4.8 years (interquartile range, 2.0–7.6). Postoperatively, 30.6% of patients (n = 59) received biologic therapy. Thirty-five patients (18.1%) had small-bowel Crohn’s disease recurrence for an estimated 5-year recurrence-free rate of 80.2% (95% CI, 73.0–85.7). Seven patients (3.6%) developed small-bowel Crohn’s disease recurrence requiring surgery for an estimated 5-year surgical recurrence-free rate of 94.7% (95% CI, 89.0–97.5). On multivariable analysis, history of small-bowel Crohn’s disease (HR 2.17; 95% CI‚ 1.04–4.54) and diagnosis at age younger than 18 years (HR 2.31; 95% CI‚1.1–4.86) were associated with small-bowel Crohn’s disease recurrence. LIMITATIONS: Retrospective design and nonstandardized follow-up. CONCLUSIONS: Patients undergoing total proctocolectomy with end ileostomy for Crohn’s disease have approximately a 20% risk of small-bowel recurrence at 5 years but a low risk of requiring surgical intervention. Patients with a history of small-bowel Crohn’s disease and younger age at diagnosis have a higher risk of recurrence and may warrant consideration of more frequent surveillance and medical prophylaxis. See Video Abstract . FACTORES DE RIESGO DE RECURRENCIA DE LA ENFERMEDAD DE CROHN DEL INTESTINO DELGADO DESPUÉS DE UNA PROCTOCOLECTOMÍA TOTAL ANTECEDENTES: El tratamiento quirúrgico de la enfermedad de Crohn del colon y el recto frecuentemente requiere proctocolectomía total con ileostomía terminal. Existe información limitada sobre la necesidad de terapia dirigida a la enfermedad de Crohn y la prevalencia de recurrencia tras la cirugía. OBJETIVO: Determinar el riesgo de recurrencia de la enfermedad de Crohn del intestino delgado y evaluar los factores de riesgo de recurrencia posoperatoria tras proctocolectomía total con ileostomía terminal. DISEÑO: Estudio de cohorte retrospectivo. ÁMBITO: Sistema de atención médica terciaria multiestatal. PACIENTES: Pacientes adultos con enfermedad de Crohn sometidos a proctocolectomía total con ileostomía terminal entre 2014 y 2023. PRINCIPALES MEDIDAS DE RESULTADO: El resultado primario fue la recurrencia de la enfermedad de Crohn del intestino delgado. RESULTADOS: Se incluyeron un total de 193 pacientes con una mediana de edad de 45 años (RIC, 34-61). Más de la mitad de los pacientes (n = 102, 52,9 %) tenían antecedentes de enfermedad de Crohn del intestino delgado y la mayoría (n = 134, 69,4 %) recibieron terapia biológica antes de la cirugía. El tiempo medio de seguimiento fue de 4,8 años (RIC, 2,0-7,6). Después de la cirugía, el 30,6 % de los pacientes (n = 59) recibieron terapia biológica. Treinta y cinco pacientes (18,1 %) tuvieron recurrencia de la enfermedad de Crohn del intestino delgado para una tasa estimada libre de recurrencia a 5 años del 80,2 % (IC del 95 %, 73,0-85,7). Siete pacientes (3,6 %) desarrollaron recurrencia de la enfermedad de Crohn del intestino delgado que requirió cirugía para una tasa estimada libre de recurrencia quirúrgica a 5 años del 94,7 % (IC del 95 %, 89,0-97,5). En el análisis multivariable, los antecedentes de enfermedad de Crohn del intestino delgado (HR 2,17; IC del 95%: 1,04-4,54) y el diagnóstico antes de los 18 años (HR 2,31; IC del 95%: 1,1-4,86) se asociaron con la recurrencia de la enfermedad de Crohn del intestino delgado. LIMITACIONES: Diseño retrospectivo y seguimiento no estandarizado. CONCLUSIONES: Los pacientes sometidos a proctocolectomía total con ileostomía terminal por enfermedad de Crohn tienen aproximadamente un 20% de riesgo de recurrencia en el intestino delgado a los 5 años, pero un bajo riesgo de requerir intervención quirúrgica. Los pacientes con antecedentes de enfermedad de Crohn del intestino delgado y menor edad al diagnóstico tienen un mayor riesgo de recurrencia y podrían requerir una vigilancia más frecuente y profilaxis médica. (AI-generated translation )

ABSTRACT Objective To compare antigen removal processing with conventional sodium dodecyl sulfate decellularization for generating laryngotracheoesophageal scaffolds, focusing on preservation of extracellular matrix integrity and removal of immunogenic material. Methods Laryngotracheoesophageal complexes were harvested from C57BL/6 mice and processed using either antigen removal or sodium dodecyl sulfate‐based protocols. Scaffolds were analyzed for residual double‐stranded DNA content, collagen preservation, glycosaminoglycan retention, and ultrastructural integrity via histology, quantitative image analysis, and scanning electron microscopy. Results Both antigen removal and sodium dodecyl sulfate protocols achieved effective decellularization, with comparable dsDNA removal relative to native controls ( p = 0.001; p < 0.001). Antigen removal scaffolds demonstrated better collagen preservation compared to sodium dodecyl scaffolds, which exhibited marked collagen depletion (Muscle: Collagen I, p < 0.001; Collagen III, p < 0.01; Cartilage: Collagen I, p < 0.05; Collagen III, p < 0.01). Both antigen removal and sodium dodecyl sulfate groups showed significant glycosaminoglycan depletion compared with controls ( p < 0.001). Scanning electron microscopy confirmed superior ultrastructural preservation in antigen removal‐treated scaffolds, characterized by intact fibrillar architecture and lacunar morphology, while sodium dodecyl sulfate scaffolds demonstrated collapsed lacunae and irregular extracellular matrix organization. Conclusion Antigen removal processing generates laryngotracheoesophageal scaffolds with enhanced extracellular matrix preservation compared with conventional sodium dodecyl sulfate decellularization, while maintaining equivalent levels of antigen elimination. Retention of collagen and ultrastructure suggests antigen removal scaffolds may provide superior biomechanical and biologic performance for laryngeal tissue engineering. Although glycosaminoglycan depletion remains a limitation in both approaches, antigen removal scaffolds represent a promising pathway toward clinically translatable alternatives to immunosuppression‐dependent laryngotracheoesophageal repair. Level of Evidence Preclinical.

This is the case of a 67-year-old immunocompetent Hispanic male residing in Mexico who presented with acute right lower back and right lateral thigh pain. Initial imaging was unremarkable. He later developed painful vesicular lesions on the right foot and buttock. He was diagnosed with herpes zoster and initiated acyclovir and gabapentin. Ten days later, he developed foot drop, leg weakness, and urinary incontinence. Magnetic resonance imaging (MRI) showed enhancement of the cauda equina, and electrodiagnostic studies demonstrated right lumbar polyradiculopathy. The patient improved significantly with pain medications and physical therapy. After 8 months of physical therapy, he demonstrated significant clinical improvement. This case highlights the uncommon presentation of motor involvement in herpes zoster and emphasizes the role of imaging and electrophysiology in guiding diagnosis and management.

Deep brain stimulation (DBS), a cornerstone neurosurgical intervention for advanced Parkinson’s disease, exerts modulatory effects on aberrant basal ganglia circuitry through continuous high-frequency electrical stimulation. This approach yields sustained amelioration of motor symptoms while concurrently reducing the requisite dosage of dopaminergic pharmacotherapy. Nonetheless, DBS still has its limitations: its efficacy on non-motor symptoms remains limited, electrode implantation leads to biological reactions, and it cannot alter the trajectory of disease progression. Embryonic stem cells and induced pluripotent stem cells can be directed to differentiate into functionally mature nigrostriatal dopaminergic neurons, demonstrating the potential for neuronal replacement and neuroprotective effects in preclinical models and early-phase clinical trials. Mesenchymal stem cells and their derived exosomes mitigate neuroinflammation and impede α-synuclein aggregation through neurotrophic support and immunomodulatory mechanisms. This article reviews two core domains that have achieved breakthroughs in the treatment of Parkinson’s disease—DBS and stem cells—and covers their current status and future prospects. First, this review elucidates the therapeutic mechanisms of DBS, including neurotransmitter release regulation and neuroinflammation suppression, while evaluating its long-term efficacy (e.g., the sustainability of motor improvement and advancements in directional stimulation technology) and safety challenges (e.g., cognitive impairment, mood disturbances, and glial scar formation induced by electrode implantation). Second, it provides an in-depth analysis of the differentiation mechanisms of stem cells from different sources (embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, etc.), preclinical efficacy validation, and early-phase clinical trial outcomes (e.g., the long-term safety and motor function enhancement observed in the transplantation of induced pluripotent stem cell-derived nigrostriatal dopaminergic progenitor cells). Third, the article addresses the standardization of stem cell therapy protocols, strategies for managing immune rejection, and current international regulatory and ethical frameworks. The core challenges of current Parkinson’s disease treatment paradigms are as follows: DBS shows limited efficacy in improving axial symptoms (e.g., freezing of gait), whereas stem cell transplantation faces issues such as low long-term graft survival and insufficient functional integration. Looking ahead, multidisciplinary integration is essential to promote the synergistic application of DBS and stem cell therapy, develop personalized treatment protocols under the guidance of precision medicine, and translate novel neural interface materials and genetic engineering technologies into clinical practice. Ultimately, such integrated strategies hold the promise of advancing Parkinson’s disease therapy from mere symptom control to true disease modification.

Background: Major depressive disorder remains a leading cause of disability. While subgenual cingulate cortex (sgCC) deep brain stimulation (DBS) shows promise for medically refractory depression, clinical outcomes have been heterogeneous, suggesting that individual differences in neural circuitry engagement may critically influence therapeutic efficacy. We aimed to define the electrophysiological signatures of sgCC efferent connectivity using single-pulse electrical stimulation (SPES) with intracranial stereo-EEG (sEEG) to inform rational targeting and physiological biomarkers for sgCC-DBS. Methods: In four patients undergoing clinically indicated sEEG for seizure mapping, SPES was delivered through sgCC pairs, while distributed brain stimulation-evoked potentials (BSEPs) were recorded across cortical and subcortical sites. Responses were characterized using Canonical Response Parameterization to extract reproducible waveforms and per-trial reliability. Results: sgCC stimulation elicited reproducible, spatially organized BSEPs across frontal, limbic, and paralimbic networks, aligning with known anatomical pathways. Frontal recruitment featured robust, lateralized orbitofrontal activation favoring the ipsilateral central, medial OFC and bilateral ventromedial prefrontal responses. Limbic effects demonstrated bilateral cingulate activation with stronger ipsilateral recruitment and lateralized amygdala and hippocampal responses. Paralimbic engagement included insular responses with subject-specific anterior predominance and bi-hemispheric temporal-polar slow-wave deflections. Conclusion: These findings provide direct electrophysiological evidence of distributed, lateralized sgCC divergent network connectivity in the human brain, offering physiologic confirmation of its role in affective circuitry. The observed topography and laterality have direct applications for sgCC-DBS targeting and implicate BSEP signatures as candidate biomarkers to guide patient-specific therapy.

The ever-changing landscape of cardiology necessitates continuous education of healthcare providers. Case-based learning (CBL) provides an inquiry-based form of learning where learners apply knowledge to realistic clinical scenarios under instructor guidance. However, current case-based learning curricula are limited to representing 3-dimensional content in 2-dimensions with distinct modalities utilized for various data sources. Virtual reality (VR) shows promise for CBL given it provides an immersive and interactive 3-dimensional medium in which multi-source content can be incorporated into a unified learning experience, potentially translating to improved learning efficiency and lower cognitive load. With VR case-based learning, learners can view medical imaging in 3-dimensions or seamlessly interact with various 2-dimensional images within one unified medium. Further, additional content including simulated patients or procedures can be incorporated with a higher level of fidelity. Herein, we summarize the current literature exploring VR-CBL, demonstrate a proof-of-concept VR application, and review the implications for cardiology education. The proof-of-concept exemplifies many of the key advantages unique to VR-CBL, such as medical imaging rendered in 3-dimensions, integration of multiple imaging sources, and novel interaction methodologies. Given the importance and rapid evolution of ongoing medical education, VR-CBL, with its immersive and engaging nature, appears to be a promising form of instruction that may serve a larger role in continuing medical education initiatives.

Abstract Background Diabetes mellitus elevates Parkinson’s disease (PD) risk, via hypothesized cerebrovascular mediation. Whether the diabetes/prediabetes vascular-risk phenotype concentrates in cardiometabolic risk or macrovascular events across prodromal and clinically diagnosed PD remains unresolved. Objectives To quantify the vascular-risk burden associated with diabetes/prediabetes across the PPMI diagnostic cohorts to test whether this association differs by cohort. Methods Cross-sectional analysis of 413 PPMI participants (76 healthy controls, 145 prodromal PD, 192 clinically diagnosed PD) examined diabetes/prediabetes (n = 73) and seven vascular risk factors. The Vascular Burden Score (0 to 7) was a priori partitioned into microvascular and macrovascular sub-scores. Modified Poisson regression estimated adjusted prevalence ratios (aPR), adjusted for age, sex, and body mass index. A cohort-by-diabetes interaction tested cross-cohort consistency. Sensitivity analyses incorporated nigral diffusion tensor imaging (PD-risk biomarker) and FreeSurfer white matter hypointensity volume (cerebrovascular marker). Results Diabetes/prediabetes elevated Vascular Burden Score (β = 0.53, 95% CI 0.29 to 0.77, p < 0.001) versus non-diabetic participants, with a non-significant cohort-by-diabetes interaction (F = 0.29, p = 0.747). Three microvascular factors survived false discovery rate correction: obesity (aPR 2.28), hypertension (aPR 1.60), and hyperlipidemia (aPR 1.45). Macrovascular events showed no diabetic amplification (β = −0.06, p = 0.25). In the imaging-phenotyped subset, Vascular Burden Score components contributed classifier variance distinct from nigral microstructure. Conclusions Diabetes/prediabetes operationalize a microvascular cluster stable across prodromal and idiopathic PD. Cardiometabolic phenotyping may complement established PD-risk biomarkers (dopamine transporter SPECT, nigral diffusion), pending longitudinal validation linking vascular phenotype to dopaminergic markers.

Objective: To synthesize the available evidence on medical therapies investigated for the management of NF2-related vestibular schwannomas (VS). Study design: Systematic review. Setting: Not applicable. Patients: NF2-related VS patients. Interventions: Systemic medical therapies. Main outcome measures: Tumor control and hearing outcomes. Results: Thirty studies met inclusion criteria: 18 investigated bevacizumab, 5 mTOR inhibitors, 5 tyrosine kinase inhibitors (TKIs), and 2 the vascular endothelial growth factor receptor (VEGFR) vaccine. Bevacizumab demonstrated the most consistent activity, with hearing improvement in up to 61% of patients, stable hearing in up to 84%, and tumor response in up to 60% (Level 4 evidence). Outcomes for mTOR inhibitors were variable, with 1 study stopped for futility, while others reported up to 100% hearing and tumor stability (Level 4 evidence). Five different TKIs showed hearing improvement rates ranging from 17 to 60% and tumor responses of 10 to 23.5% (Level 4 evidence). The VEGFR vaccine appeared safe and immunologically active, with radiologic and hearing improvement in one-third of patients (Level 4 evidence). Conclusions: Bevacizumab remains the most studied and clinically active systemic therapy for NF2-related VS, although evidence is largely nonrandomized. Other systemic therapies have demonstrated variable results in terms of hearing outcomes or tumor control. High-quality prospective and randomized controlled trials are needed to clarify efficacy, durability, and comparative effectiveness.