Citations

Abstract Rationale Fibrosing mediastinitis (FM) is an uncommon fibroinflammatory condition without established or effective medical therapies. Infiltrating B lymphocytes are commonly present, and progressive fibrosis compromises mediastinal structures, including blood vessels and airways, resulting in significant morbidity and mortality. Objective To evaluate the benefits and side effects of rituximab in patients with progressive and symptomatic FM. Methods We treated 22 patients (median age, 35 yr; range, 15–68 yr; 45% female) with metabolically active, progressive FM with rituximab on an off-label basis. Additionally, patients were administered pneumocystis and antifungal prophylaxis when immunosuppressed with rituximab. Modeling of longitudinal treatment response based on changes in relative lesion volume from baseline was performed retrospectively using functional data analysis, and time-to-event modeling was performed to estimate treatment response rates based on a >30% reduction in pretreatment volume. The primary endpoints were lack of disease progression and change in mediastinal lesion volume on computed tomography (evaluated retrospectively). Results No patient experienced disease progression after rituximab therapy. Median clinical follow-up was 42 months (range, 7–94 mo) and imaging follow-up 21 months (range, 7–62 mo). A total of 82% of patients had confirmed histoplasmosis-associated FM. After rituximab treatment, a 49.6% (95% confidence interval, 17.5–64.4%) mean estimated decrease in pretreatment lesion volume was observed at 24 months. The estimated objective treatment response rate was 47.9% (95% confidence interval, 26.7–70.3%). Conclusions This observational study suggests that rituximab is a well tolerated and potentially effective therapy in a cohort of patients with symptomatic and progressive FM.

Bi-allelic disruptive variants (nonsense, frameshift, and splicing variants) in KDM5B have been identified as causative for autosomal recessive intellectual developmental disorder type 65. In contrast, dominant variants, usually disruptive as well, have been more difficult to implicate in a specific phenotype, since some of them have been found in unaffected controls or relatives. Here, we describe individuals with likely pathogenic variants in KDM5B, including eight individuals with dominant missense variants. This study is a retrospective case series of 21 individuals with variants in KDM5B. We performed deep phenotyping and collected the clinical information and molecular data of these individuals’ family members. We compared the phenotypes according to variant type and to those previously described in the literature. The most common features were developmental delay, impaired intellectual development, behavioral problems, autistic behaviors, sleep disorders, facial dysmorphism, and overgrowth. DD, ASD behaviors, and sleep disorders were more common in individuals with dominant disruptive KDM5B variants, while individuals with dominant missense variants presented more frequently with renal and skin anomalies. This study extends our understanding of the KDM5B-related neurodevelopmental disorder and suggests the pathogenicity of certain dominant KDM5B missense variants.

AbstractEndoluminal radiofrequency ablation (RFA) is a palliative treatment for patients suffering from malignant biliary obstruction (MBO). We aimed to conduct a meta-analysis to evaluate the impact of RFA on stent patency, patient survival, and adverse events.Major databases were searched through December 2023 for patients who had undergone stenting with or without RFA for extrahepatic MBO. A random-effects model was used for analysis, with results expressed as relative risk ratios (RRs) with 95%CIs.Nine RCTs involving 750 subjects with MBO (374 RFA plus stent vs. 376 stent only) were included. Meta-analysis revealed similar risks of stent patency at 3 months (RR 1.01, 95%CI 0.92–1.11; I 2 = 4%) for RFA plus stenting vs. stent only. Meta-analysis showed improved survival at 6 months (RR 0.84, 95%CI 0.73–0.96; I 2 = 21%; P = 0.01) for RFA plus stenting vs. stent only. Subgroup analysis comparing plastic vs. uncovered metal stents showed that stent patency was unaffected at 3 months (RR 1.06, 95%CI 0.91–1.23; I 2 = 17%). Subgroup analysis showed that patients with cholangiocarcinoma experienced an overall survival benefit with RFA plus stenting vs. stenting alone (P < 0.001); however, stent patency remained unaffected (P = 0.08). An increased incidence of cholecystitis was noted with RFA plus stenting vs. stenting alone (5.1% [95%CI 3.1%–7.8%] vs. 0.3% [95%CI 0.01%–1.5%], respectively).Combining endoluminal RFA and stenting may improve overall survival in patients with MBO. RFA did not significantly impact stent patency.

BACKGROUND: IPAA has become the criterion standard for treating ulcerative colitis, familial adenomatous polyposis, and selected cases of Crohn’s colitis. Robotic surgery promises improved postoperative outcomes and decreased length of stay. However, few studies have evaluated the benefits of robotic IPAA compared to laparoscopy. OBJECTIVE: To compare short-term 30-day postoperative outcomes of robotic versus laparoscopic proctectomy with IPAA and diverting loop ileostomy. DESIGN: Retrospective observational study from a single, high-volume center. SETTINGS: Mayo Clinic, Rochester, Minnesota (tertiary referral center for IBD). PATIENTS: All adult patients undergoing minimally invasive proctectomy with IPAA and diverting loop ileostomy between January 2015 and April 2023. MAIN OUTCOME MEASURES: Thirty-day complications, hospital length of stay, estimated blood loss, conversion rate, 30-day readmission, and 30-day reoperation. RESULTS: Two hundred seventeen patients were included in the study; 107 underwent robotic proctectomy with IPAA and diverting loop ileostomy, whereas 110 had laparoscopic proctectomy with IPAA and diverting loop ileostomy. Operating time was significantly longer in the robotic group (263 ± 38 vs 228 ± 75 minutes, p < 0.0001). The robotic group also had lower estimated blood loss (81.5 ± 77.7 vs 126.8 ± 111.0 mL, p = 0.0006) as well as fewer conversions (0% vs 8.2%, p = 0.003). Patients in the robotic group received more intraoperative fluids (3099 ± 1140 vs 2472 ± 996 mL, p = 0.0001). However, there was no difference in length of stay, 30-day morbidity, 30-day readmission, 30-day reoperation, rate of diverting loop ileostomy closure at 3 months, and surgical IPAA complication rate after ileostomy closure. LIMITATIONS: Retrospective design, single-center study, potential bias because of the novelty of the robotic approach, and lack of long-term and quality-of-life outcomes. CONCLUSIONS: Robotic proctectomy with IPAA and diverting loop ileostomy may offer advantages in terms of estimated blood loss and conversion rate while maintaining the benefits of minimally invasive surgery. Further research is needed to evaluate long-term outcomes. See Video Abstract. NAVEGANDO EL PROGRESO: EXPERIENCIA DE OCHO AÑOS EN UN SOLO CENTRO CON PROCTECTOMÍA MÍNIMAMENTE INVASIVA Y ANASTOMOSIS ANAL-BOLSA ILEAL ANTECEDENTES: La anastomosis anal-bolsa ileal (IPAA) se ha convertido en el estándar de oro para el tratamiento de la colitis ulcerosa, la poliposis adenomatosa familiar y casos seleccionados de colitis de Crohn. La cirugía robótica promete mejores resultados posoperatorios y una menor duración de la estancia hospitalaria. Sin embargo, pocos estudios han evaluado los beneficios de la IPAA robótica en comparación con la laparoscopia. OBJETIVO: Comparar los resultados postoperatorios a corto plazo a 30 días de la proctectomía robótica versus laparoscópica con IPAA e ileostomía en asa de derivación. DISEÑO: Estudio observacional retrospectivo de un único centro de gran volumen. AJUSTES: Mayo Clinic, Rochester, Minnesota (centro terciario de referencia para EII). PACIENTES: Todos los pacientes adultos sometidos a proctectomía mínimamente invasiva con IPAA y DLI entre Enero de 2015 y Abril de 2023. PRINCIPALES MEDIDAS DE RESULTADOS: Complicaciones a los 30 días, duración de la estancia hospitalaria, pérdida de sangre estimada, tasa de conversión, reingreso a los 30 días y reoperación a los 30 días. RESULTADOS: Se incluyeron en el estudio 217 pacientes; 107 se sometieron a proctectomía robótica con IPAA y DLI, mientras que 110 se sometieron a proctectomía laparoscópica con IPAA y DLI. El tiempo operatorio fue significativamente mayor en el grupo robótico (263 ± 38 minutos versus 228 ± 75 minutos, p < 0,0001); la pérdida de sangre estimada (EBL) fue menor en el grupo robótico (81,5 ± 77,7 ml versus 126,8 ± 111,0 ml, p = 0,0006), así como el número de conversiones (0% versus 8,2%, p = 0,003). Los pacientes del grupo robótico recibieron más líquidos intraoperatorios (3099 ± 1140 ml versus 2472 ± 996 ml, p = 0,0001). Sin embargo, no hubo diferencias en la duración de la estancia hospitalaria, la morbilidad a los 30 días, el reingreso a los 30 días, la reoperación a los 30 días, la tasa de cierre del DLI a los tres meses y la tasa de complicaciones quirúrgicas de la IPAA después del cierre de la ileostomía. LIMITACIONES: Diseño retrospectivo, estudio unicéntrico, posible sesgo debido a la novedad del enfoque robótico, falta de resultados a largo plazo y de calidad de vida. CONCLUSIONES: La proctectomía robótica con IPAA y DLI puede ofrecer ventajas en términos de EBL y tasa de conversión, manteniendo al mismo tiempo los beneficios de la cirugía mínimamente invasiva. Se necesita más investigación para evaluar los resultados a largo plazo. (Traducción—Dr. Yesenia Rojas-Khalil)

ABSTRACT The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus.

Study Design. Retrospective review of prospectively collected data. Objective. The aim of this study was to investigate what factors predict delayed improvement after surgical treatment of low-grade spondylolisthesis. Summary of Background Data. Lumbar surgery leads to clinical improvement in the majority of patients with low-grade spondylolisthesis. Most patients improve rapidly after surgery, but some patients demonstrate a delayed clinical course. Methods. The Quality and Outcomes Database (QOD) was queried for grade 1 spondylolisthesis patients who underwent surgery who had patient-reported outcome measures (PROMs) collected at baseline, 3, 6, and 12 months, including back and leg pain Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), and EuroQol-5D (EQ-5D). Patients were stratified as “early responders” reaching MCID at 3 months and maintaining improvement through 12 months and “delayed responders” not reaching MCID at 3 months but ultimately reaching MCID at 12 months. These two groups were compared with respect to factors which predicted delayed improvement. Results. Of 608 patients enrolled, 436 (72%) met inclusion criteria for this study. Overall, 317 patients (72.7%) reached MCID for ODI at 12 months following surgery. Of these patients, 249 (78.5%) exhibited a rapid clinical improvement trajectory and had achieved ODI MCID threshold by the 3-month postoperative follow-up. Sixty-eight patients (21.4%) showed a delayed trajectory, and had not achieved ODI MCID threshold at 3 months, but did ultimately reach MCID at 12-month follow-up. Factors associated with delayed improvement included impaired preoperative ambulatory status, better baseline back and leg pain scores, and worse 3-month leg pain scores ( P <0.01). Conclusions. The majority of patients undergoing surgery for low-grade spondylolisthesis reach ODI MCID threshold rapidly, within the first 3 months after surgery. Factors associated with a delayed clinical course include impaired preoperative ambulation status, relatively better preoperative back and leg pain, and persistent leg pain at 3 months.

BACKGROUND Policy changes to Mohs micrographic surgery board certification eligibility and population shifts in the wake of the COVID-19 pandemic have significant implications for the accessibility of Mohs micrographic surgeons across the United States. OBJECTIVE To examine the geographic distribution of micrographic surgery providers considering recent population trends and assess the impact of certification eligibility changes and population shifts on accessibility. METHODS AND MATERIALS Medicare claims data were utilized to identify micrographic surgery providers. Surgeon densities were calculated per 100,000 people by county and state. Population changes were analyzed using US census data. RESULTS Practicing micrographic surgeons were concentrated in metropolitan and nonmetropolitan areas. Overall, 80.4% of counties lacked micrographic surgery providers, with rural areas being the most underserved. Population changes varied among states. CONCLUSION Shifts in micrographic surgery certification requirements, US population distribution, and micrographic surgeon location emphasize challenges in accessibility, especially in rural areas across the United States.

Acute kidney injury (AKI) frequently complicates the course of hospitalized patients with cirrhosis and negatively affects their prognosis. How AKI response influences the timing of liver transplantation (LT) remains unclear. We sought to assess the impact of AKI response to treatment on survival and LT rates in patients with cirrhosis awaiting LT. This was a retrospective multicenter study of cirrhosis patients waitlisted for LT and hospitalized with AKI in 2019. The exposure was AKI response versus no response during hospitalization. Outcomes were 90-day overall and transplant-free survival, and rates of LT with time to transplant. We adjusted for age, sex, race, cirrhosis etiology, site, and Model for End-Stage Liver Disease-Sodium (MELD-Na) score. Among the 317 patients in this study, 170 had an AKI response (53.6%), and 147 had no response (46.4%). Compared to nonresponders, responders had better 90-day overall survival (89.4% vs. 76.2%, adjusted subhazard ratio for mortality 0.34, p=0.001), and transplant-free survival (63.5% vs. 25.2%, aHR for probability of death or transplant 0.35, p<0.001). The LT rate was lower in responders (45.9% vs. 61.2%, adjusted subhazard ratio 0.55, p=0.005); 79% of transplants in responders occurred after discharge, at a median of 103 days, while 62% of transplants in nonresponders occurred during hospitalization, with the remainder occurring postdischarge at a median of 58 days. In patients with cirrhosis waitlisted for LT who are hospitalized with AKI, AKI response to therapy is associated with improved 90-day survival, despite a reduced LT rate and longer time to LT.

Socioeconomic status (SES) is a multi‐faceted theoretical construct associated with stroke risk and outcomes. Knowing which SES measures best correlate with population stroke metrics would improve its accounting in observational research and inform interventions. Using the Centers for Disease Control and Prevention's (CDC) Population Level Analysis and Community Estimates (PLACES) and other publicly available databases, we conducted an ecological study comparing correlations of different United States county‐level SES, health care access and clinical risk factor measures with age‐adjusted stroke prevalence. The prevalence of adults living below 150% of the federal poverty level most strongly correlated with stroke prevalence compared to other SES and non‐SES measures (correlation coefficient = 0.908, R2 = 0.825; adjusted partial correlation coefficient: 0.589, R2 = 0.347). ANN NEUROL 2024;96:739–744