Citations

ABSTRACT Background: Anal fistulas remain challenging in colorectal surgery, with recurrence and postoperative incontinence common despite advances in treatment. Multiple classification systems exist, but their predictive value for surgical and functional outcomes is unclear. Aims: The aim of this study was to compare Parks, American Society of Colon and Rectal Surgeons (ASCRS), and St. James’s University Hospital (SJUH) MRI-based classifications in predicting surgical outcomes, including continence preservation. Methods: Retrospective analysis of 89 patients undergoing definitive surgical treatment for anorectal fistulas at a single referral center (2012–2019). Exclusions included rectovaginal fistulas, Crohn’s disease, or prior pelvic radiotherapy. Fistulas were classified using Parks, ASCRS, and, when available, SJUH (n=49). Outcomes included the number of procedures, type of initial procedure, fistula closure, and closure without continence deterioration. Continence was assessed using the Cleveland Clinic Jorge-Wexner score. Results: Most fistulas were transsphincteric (Parks Type 2, 62%) and complex (ASCRS, 65%). Overall, 86.5% achieved fistula closure, and 73% achieved closure without continence deterioration. Parks and ASCRS were significantly associated with fistula closure with continence preservation (p=0.008 and 0.007, respectively) and type of initial procedure. Parks remained significant when considering closure alone (p=0.005), while ASCRS showed a borderline association (p=0.051). SJUH classification was associated only with procedure selection. Conclusions: Parks and ASCRS classifications were associated with fistula closure with continence preservation and type of initial procedure. Considering closure alone, only Parks remained significant. SJUH was limited to procedure selection. Overall, Parks and ASCRS guide surgical planning and prediction of functional outcomes, with Parks slightly more sensitive.

Abstract INTRODUCTION White matter lesions on fluid‐attenuated inversion recovery magnetic resonance imaging (FLAIR‐MRI) reflect small vessel disease (SVD) and aid in identifying vascular contributions to impairment and dementia (VCID). Emerging diffusion MRI (dMRI) biomarkers are sensitive to early SVD but the lack of validated approaches for defining dMRI abnormality has limited their clinical utility. METHODS In 3934 participants (8749 observations) from a population‐based sample, we classified 9% as vascular cognitive impairment versus not (VCI+/VCI−) using abnormal FLAIR‐MRI and cognitive testing. We evaluated four distinct dMRI positivity criteria and assessed performance in an independent clinical sample. RESULTS The young referent criterion performed best and yielded an estimated prevalence of dMRI positivity aligned with pathology literature. About 40% of the population were dMRI positive, and these individuals had lower baseline cognition and faster longitudinal decline. Cutpoints were validated in an independent clinical sample. DISCUSSION The proposed dMRI abnormality framework can detect VCID and aid in identification of individuals at risk of VCI.

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.