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BACKGROUND: Pelvic exenteration is the treatment of choice for selected patients with locally advanced primary and recurrent rectal cancer. Involvement of major pelvic neurovascular structures and bone was historically considered a contraindication due to unacceptably high rates of morbidity and low R0 resection rates. OBJECTIVE: To compare the outcomes of these “high-complexity” exenterative resections to those of “conventional” pelvic exenteration. DESIGN: International multicenter retrospective cohort study. SETTINGS: Sixteen specialized exenteration centers. PATIENTS: Those who underwent total pelvic exenteration for locally advanced primary and recurrent rectal cancer between 2018 and 2023 at participating centers. MAIN OUTCOME MEASURES: Perioperative resource utilization, morbidity, mortality, and R0 resection rates were reported. RESULTS: Seven hundred sixty-three patients underwent total pelvic exenteration, of whom 478 (63%) and 285 (37%) required conventional and high-complexity procedures, respectively. High-complexity pelvic exenteration was associated with longer operating time (600 vs 480 minutes, p < 0.001 for locally advanced primary rectal cancer, 623 vs 480 minutes, p < 0.001 for locally recurrent rectal cancer), intensive care stay (2 vs 1 day, p < 0.001 and 3 vs 1 day, p < 0.001), hospital stay (19 vs 15 days, p = 0.008 and 23 vs 15 days, p < 0.001), and higher blood loss (2000 vs 1236 mL, p < 0.001 and 3000 vs 1600 mL, p < 0.001). Morbidity and mortality outcomes and R0 resection rates were similar between the groups. LIMITATIONS: Generalizability of findings outside of expert units. CONCLUSIONS: High-complexity pelvic exenteration for the treatment of rectal cancer is associated with similar morbidity, mortality, and R0 resection rates, but it has a significantly higher operative time, blood loss, and hospital resource utilization compared to conventional pelvic exenteration. In high-volume, specialized centers, these techniques are considered the standard of care for appropriately selected patients with tumors that involve major pelvic bone or neurovascular structures. See Video Abstract . EXENTERACIÓN PÉLVICA TOTAL CONVENCIONAL FRENTE A EXENTERACIÓN PÉLVICA TOTAL DE ALTA COMPLEJIDAD PARA EL CÁNCER RECTAL LOCALMENTE AVANZADO Y LOCALMENTE RECURRENTE: UN ESTUDIO MULTICÉNTRICO INTERNACIONAL ANTECEDENTES: La exenteración pélvica es el tratamiento de elección para determinados pacientes con cáncer rectal primario y recurrente localmente avanzado. La afectación de las principales estructuras neurovasculares y óseas pélvicas se consideraba históricamente una contraindicación debido a las tasas inaceptablemente altas de morbilidad y a las bajas tasas de resección R0. OBJETIVO: Comparar los resultados de estas resecciones exenteración «de alta complejidad» con los de la exenteración pélvica «convencional». DISEÑO: Estudio de cohorte retrospectivo multicéntrico internacional. ENTORNOS: Dieciséis centros especializados en exenteración. PACIENTES: Aquellos que se sometieron a una exenteración pélvica total por cáncer rectal primario y recurrente localmente avanzado entre 2018 y 2023 en los centros participantes. PRINCIPALES MEDIDAS DE RESULTADOS: Se informaron la utilización de recursos perioperatorios, la morbilidad, la mortalidad y las tasas de resección R0. RESULTADOS: 763 pacientes se sometieron a una exenteración pélvica total, de los cuales 478 (63 %) y 285 pacientes (37 %) requirieron procedimientos convencionales y de alta complejidad, respectivamente. La exenteración pélvica de alta complejidad se asoció con un tiempo quirúrgico más prolongado (600 frente a 480 minutos, p < 0,001 para el cáncer rectal primario localmente avanzado, 623 frente a 480 minutos, p < 0,001 para el cáncer rectal localmente recurrente), estancia en cuidados intensivos (2 frente a 1 día, p < 0,001 y 3 frente a 1 día, p < 0,001), estancia hospitalaria (19 frente a 15 días, p = 0,008 y 23 frente a 15 días, p < 0,001) y mayor pérdida de sangre (2000 frente a 1236 ml, p < 0,001 y 3000 frente a 1600 ml, p < 0,001). Los resultados de morbilidad y mortalidad, así como las tasas de resección R0, fueron similares entre los grupos. LIMITACIONES: Generalización de los resultados fuera de las unidades especializadas CONCLUSIONES: La exenteración pélvica de alta complejidad para el tratamiento del cáncer de recto se asocia con tasas similares de morbilidad, mortalidad y resección R0, pero con un tiempo quirúrgico, una pérdida de sangre y una utilización de recursos hospitalarios significativamente mayores en comparación con la exenteración pélvica convencional. En centros especializados con un gran volumen de casos, estas técnicas se consideran el tratamiento estándar para pacientes adecuadamente seleccionados con tumores que afectan a los huesos pélvicos principales o a las estructuras neurovasculares. ( AI-generated translation )

ABSTRACT Femoroacetabular impingement (FAI) of the hip results from altered morphology of the proximal femur and/or acetabulum, creating abnormal contact between these structures during normal hip range of motion. The etiology of this structural phenotype is unknown. This study aimed to identify common single‐nucleotide variants (SNVs) among two families with seemingly heritable FAI. Additionally, this study examined biologic networks among proteins encoded by identified SNVs and surveyed the literature regarding the role of these proteins in musculoskeletal development. Methodologically, blood samples were collected from affected and unaffected members of two separate families with a pattern of heritable FAI. Exome sequencing identified SNVs, and a protein–protein interaction network assessment, in addition to a literature review, was performed to better understand the role of variant‐associated genes in musculoskeletal development. Results showed 33 and 43 variant‐associated genes affected in Family 1 and Family 2, respectively. Although no overlap in variant‐associated genes was found between families, network analysis showed that variant‐associated genes are functionally interconnected and are known to interact with each other. Furthermore, the variant‐associated genes are broadly associated with musculoskeletal development. Ultimately, genetic analysis of two families of multiple generations of FAI revealed variations in genes regulating musculoskeletal development, with several being critical local regulators of bone morphogenesis.

ABSTRACT The World Health Organization (WHO) 5th Edition and International Consensus Classification (ICC) have continued to delineate more genetically defined acute leukemias. Both recognize genetic aberrations associated with myelodysplastic syndromes/neoplasms (MDS) as defining MDS‐related AML (AML‐MR). Mutations in RUNX1 are included in this category in the ICC, but not WHO. The current classifications are unclear on how acute leukemias with ambiguous lineage (ALAL), including those of mixed lineage (MPAL) and those without a defined lineage (AUL), should be categorized in the presence of such mutations. Our multi‐institutional study aims to determine the significance of RUNX1 mutation in ALAL compared to de novo AML. Newly diagnosed MPAL, AUL, and AML with RUNX1 mutations were collected. ALAL with MDS‐related cytogenetics, BCR::ABL1 , KMT2A rearrangements, or ZNF384 or BCL11b abnormalities were excluded. We analyzed 17 cases of ALAL and 71 cases of AML that met inclusion criteria. ALAL‐ RUNX1 and AML‐ RUNX1 showed overlapping mutational landscapes with frequent comutations in MDS‐associated genes. No ALAL‐ RUNX1 or AML‐ RUNX1 cases showed concomitant TP53 mutation. ALAL‐ RUNX1 had more bone marrow blasts and more karyotypic abnormalities; however, neither impacted survival, nor did RUNX1 variant allele frequency (VAF). Survival analysis revealed similarly poor outcomes between them. AML‐directed therapies and allogeneic hematopoietic stem cell transplant trended toward improved survival in ALAL‐ RUNX1; however, it did not reach significance. Our results suggest ALAL‐ RUNX1 is associated with younger age, higher blasts, and more karyotypic abnormalities, but has similar clinical and genetic features and outcomes to AML‐ RUNX1 . Our findings suggest, like other MR mutations, RUNX1 ‐mutated ALALs should be included within AML‐MR.

Abstract Our understanding of Alzheimer's disease (AD) and related dementias (ADRD) has grown exponentially, thanks to significant investments by the National Institute on Aging (NIA). This article celebrates the 40th anniversary of the NIA's Alzheimer's Disease Research Centers, highlighting the pivotal role of neuropathology as the bedrock for neurodegeneration research. Neuropathology has championed the key principles of proteinopathy, selective vulnerability, and stereotypic spread. Furthermore, neuropathologic studies advanced our understanding of ADRD prevalence, heterogeneity, clinical–pathological correlations, and genetic underpinnings, spurring biomarker development for target engagement and disease monitoring. Disease‐modifying therapies for AD were inspired and informed by neuropathology. The neuropathology community is poised to refine diagnostics, leveraging digital pathology and integrating genetics and pathomics to enhance subtyping for novel precision medicine approaches. Despite some common misconceptions and logistical challenges, neuropathology continues to be a critical component of the ADRD research infrastructure, serving as a key bridge between allied basic and clinical sciences. Highlights We celebrate 40 years of NIA‐funded ADRCs and their contributions through neuropathology studies that have significantly advanced our understanding and treatment of ADRD. Neuropathology uncovers principles of neurodegenerative disease: proteinopathy, selective vulnerability, and stereotypic spread, informing diagnostics and therapies. Development of AD biomarkers with reference to neuropathology enhances accuracy in diagnosis and monitoring, paving the way for targeted disease‐modifying therapies. Integration of digital pathology, genetics, and novel tools in neurodegeneration research promises advanced precision medicine approaches and refined diagnostics. Misconceptions and logistical challenges to neuropathological research are addressed to improve understanding and collaboration.

Background Carpal tunnel release (CTR) is one of the most frequently performed procedures in the United States, with both open (OCTR) and endoscopic (ECTR) techniques widely used. As surgical practices evolve and outpatient care expands, understanding future utilization trends across care settings is increasingly important. This study projects the use of OCTR and ECTR through 2040 to inform shifting surgical preferences and healthcare demands. Methods This study analyzed procedural data from 2010 to 2019 using the PearlDiver Mariner all-payer claims database. Cases of OCTR and ECTR were identified using Current Procedural Terminology codes. Procedures were further stratified by inpatient or outpatient status based on the documented site of service field within the database. Log-linear, Poisson, negative binomial regression, and autoregressive integrated moving average (ARIMA) models were applied to procedural volumes to project trends through 2040. The ARIMA model was selected based on the lowest normalized root mean square error and overall model performance. Results In 2019, there were 31,190 outpatient ECTR, 155 inpatient ECTR, 101,334 outpatient OCTR, and 1359 inpatient OCTR procedures. By 2040, outpatient ECTR is projected to grow to 65,072 cases (95% CI, 62,471–67,781) at 3.79% annually. Inpatient ECTR is projected to reach 181 cases (95% CI, 97–340) with 2.13% annual growth. Outpatient OCTR is expected to decline to 77,834 cases (95% CI, 76,287–79,413), and inpatient OCTR to 962 cases (95% CI, 809–1143), with annual decreases of 1.19% and 1.48%, respectively. Conclusions By 2040, demand for outpatient ECTR is projected to increase by 110.31% compared to 2019, whereas outpatient OCTR is expected to decline by 20.31%. Although inpatient utilization remains limited, the adoption of endoscopic techniques is anticipated to rise across all care settings, in contrast to the continued decline of open procedures. These trends highlight the ongoing shift toward minimally invasive, ambulatory surgical care. Strategic planning in surgical training, healthcare infrastructure, and reimbursement models will be critical to meet changing demands. Further research is needed to validate these projections in broader populations and across diverse healthcare systems.

A peripheral nerve or spinal cord injury is a rare but significant complication of regional anesthesia. Evaluation of acute nerve injury includes a focused history and examination to localize the lesion. Confirmatory testing should include electromyography and appropriate imaging. In most cases magnetic resonance imaging (MRI) is preferred to computed tomography (CT) or ultrasound given the better resolution of the nerves and soft tissue. Most cases of peripheral nerve injury will improve and resolve without deficit. In mild cases reassurance and observation is all that is necessary. In more severe cases, if the deficit is progressive or complete, surgical exploration should be considered. If there is no recovery by 2 to 5 months then referral to a peripheral nerve surgeon should be considered. The prognosis for cauda equina or spinal cord lesions is more guarded. Recovery from these is commonly incomplete. Early diagnosis and intervention is the key to preventing catastrophic neurological outcomes.

ABSTRACT Background Patients with cancer undergoing cardiac implantable electronic device (CIED) implantation face unique challenges. This study evaluates the outcomes and implications of CIED implantation in this population. Methods Using data from the National Readmission Database (NRD) from 2016 to 2019, we analyzed CIED implantations in patients aged ≥18 years, categorized by cancer status: no cancer, historical cancer, and active cancer. Multivariable logistic and linear regression models assessed associations with in‐hospital, 30‐day, and 90‐day outcomes, adjusting for various patient characteristics. Results A total of 748,957 CIED procedures were analyzed among which 13.3% were in patients with historical cancer and 3.8% with active cancer. Active cancer was linked to higher odds of pacemaker implantation but lower odds for ICD and CRT devices. Patients with active cancer experienced higher index hospitalization mortality (aOR 1.68; 1.50–1.89; p < 0.001), major adverse cardiovascular events (aOR 1.07; 1.02–1.14; p = 0.01), bleeding (aOR 1.36; 1.27–1.46; p < 0.01), and sepsis‐related (aOR 1.31; 1.19–1.44; p < 0.01) complications, with increased readmission rates at 30 (aOR 1.37; 1.30–1.44; p < 0.01) and 90 days (aOR 1.37; 1.31–1.44; p < 0.01) compared to those without cancer. Historical cancer was associated with better outcomes. Key predictors of adverse outcomes included chronic heart failure, kidney disease, cerebrovascular disease, and protein‐calorie malnutrition. Conclusions Patients with active cancer undergoing CIED implantation have an increased risk of in‐hospital complications and readmissions as compared to those without cancer.