Citations

AbstractBackgroundResection of colorectal liver metastasis (CLM) is beneficial when feasible. However, the benefit of second hepatectomy for hepatic recurrence in CLM remains unclear.MethodsThe Colorectal Liver Operative Metastasis International Collaborative retrospectively examined 1004 CLM cases from 2000 to 2018 from a total of 953 patients. Hepatic recurrence after initial hepatectomy was identified in 218 patients. Kaplan–Meier analysis was performed for overall survival (OS) and recurrence‐free survival (RFS). Propensity score matching (PSM) was performed to offset selection bias. Cox proportional‐hazards regression was performed to identify risk factors associated with OS.ResultsA total of 51 patients underwent second hepatectomy. Unadjusted median OS was 60.1 months in repeat‐hepatectomy versus 38.3 months in the single‐hepatectomy group (p = 0.015). In the PSM population, median OS remained significantly better in the repeat‐hepatectomy group (60.1 vs. 33.1 months; p = 0.0023); median RFS was 12.4 months for the repeat‐hepatectomy group, versus 9.8 months in the single‐hepatectomy group (p = 0.0050). Repeat hepatectomy was associated with lower risk of death (hazard ratio: 0.283; p = 0.000012). Obesity, tobacco use, and high intraoperative blood loss were associated with significant risk of death (p < 0.05).ConclusionIn CLM with hepatic recurrence, second hepatectomy was beneficial for OS. With PSM, the OS benefit of performing a second hepatectomy remained significant.

NOTCH1 belongs to the NOTCH family of proteins that regulate cell fate and inflammatory responses. Somatic and germline NOTCH1 variants have been implicated in cancer, Adams‐Oliver syndrome, and cardiovascular defects. We describe 7 unrelated patients grouped by the presence of leukoencephalopathy with calcifications and heterozygous de novo gain‐of‐function variants in NOTCH1. Immunologic profiling showed upregulated CSF IP‐10, a cytokine secreted downstream of NOTCH1 signaling. Autopsy revealed extensive leukoencephalopathy and microangiopathy with vascular calcifications. This evidence implicates that heterozygous gain‐of‐function variants in NOTCH1 lead to a chronic central nervous system (CNS) inflammatory response resulting in a calcifying microangiopathy with leukoencephalopathy. ANN NEUROL 2022;92:895–901

Abstract Background Crohn’s disease (CD) is a chronic progressive condition that is complicated by intestinal or colonic stricture in nearly 30% of cases within 10 years of the initial diagnosis. Endoscopic balloon dilation (EBD) is associated with a risk of perforations and recurrence rates of up to 60% at 5 years. Endoscopic stenting has been used as an alternative to EBD, but data on its safety and efficacy are limited. We conducted a systematic review and meta-analysis to assess the outcomes of endoscopic stenting in CD-related strictures. Methods A systematic and detailed search was run in January 2022 with the assistance of a medical librarian for studies reporting on outcomes of endoscopic stenting in CD-related strictures. Meta-analysis was performed using random-effects model, and results were expressed in terms of pooled proportions along with relevant 95% confidence intervals (CIs). Results Nine studies with 163 patients were included in the final analysis. Self-expanding metal stents (SEMS) including both partial and fully covered were used in 7 studies, whereas biodegradable stents were used in 2 studies. Pooled rate of clinical success and technical success was 60.9% (95% CI, 51.6-69.5; I2 = 13%) and 93% (95% CI, 87.3-96.3; I2 = 0%), respectively. Repeat stenting was needed in 9.6% of patients (95% CI, 5.3-16.7; I2 = 0%), whereas pooled rate of spontaneous stent migration was 43.9% (95% CI, 11.4-82.7; I2 = 88%). Pooled incidence of overall adverse events, proximal stent migration, perforation, and abdominal pain were 15.7%, 6.4%, 2.7%, and 17.9%, respectively. Mean follow-up period ranged from 3 months to 69 months. Discussion Endoscopic stenting in CD-related strictures is a safe technique that can be performed with technical ease, albeit with a limited clinical success. Postprocedure abdominal pain and proximal stent migration are some of the common adverse events reported.

Abstract Objective. To investigate synchrotron-based proton pencil beam scanning (PBS) beam delivery time (BDT) using novel continuous scanning mode. Approach. A BDT calculation model was developed for the Hitachi particle therapy system. The model was validated against the measured BDT of 36 representative clinical proton PBS plans with discrete spot scanning (DSS) in the current Hitachi proton therapy system. BDTs were calculated with the next generation using Mayo Clinic Florida system operating parameters for conventional DSS, and novel dose driven continuous scanning (DDCS). BDTs of DDCS with and without Break Spots were investigated. Main results. For DDCS without Break Spots, the use of Stop Ratio to control the transit dose largely reduced the beam intensity and consequently, severely prolonged the BDT. DDCS with Break Spots was able to maintain a sufficiently high beam intensity while controlling transit dose. In DDCS with Break Spots, tradeoffs were made between beam intensity and number of Break Spots. Therefore, BDT decreased with increased beam intensity but reached a plateau for beam intensity larger than 10 MU s −1 . Averaging over all clinical plans, BDT was reduced by 10% for DDCS with Break Spots compared to DSS. Significance. DDCS with Break Spots reduced BDT. DDCS has the potential to further reduce BDT under the ideal scenario which requests both stable beam intensity extraction and accurately modelling the transit dose. Further investigation is warranted.

Abstract Research on the care of inflammatory bowel disease (IBD) patients has been primarily in populations of European ancestry. However, the incidence of IBD, which comprises Crohn’s disease and ulcerative colitis, is increasing in different populations around the world. In this comprehensive review, we examine the epidemiology, clinical presentations, disease phenotypes, treatment outcomes, social determinants of health, and genetic and environmental factors in the pathogenesis of IBD in Black and Hispanic patients in the United States. To improve health equity of underserved minorities with IBD, we identified the following priority areas: access to care, accurate assessment of treatment outcomes, incorporation of Black and Hispanic patients in therapeutic clinical trials, and investigation of environmental factors that lead to the increase in disease incidence.

AbstractIntroductionAtrial fibrillation (AF) is the most common cardiac arrhythmia with a high stroke and mortality rate. The video‐assisted thoracoscopic radiofrequency pulmonary vein ablation is a treatment option for patients who fail catheter ablation. Randomized data comparing surgical versus catheter ablation are limited. We performed a meta‐analysis of randomized control trials to explore the outcome efficacy between surgical and catheter radiofrequency pulmonary vein ablation in patients with AF.MethodsWe comprehensively searched the databases of MEDLINE and EMBASE from inception to December 2020. Included studies were published randomized control trials that compared video‐assisted thoracoscopic and catheter radiofrequency pulmonary vein ablation. Data from each study were combined using the fixed‐effects, generic inverse variance method of DerSimonian, and Laird to calculate odds ratios and 95% confidence intervals.ResultsSix studies from November 2013 to 2020 were included in this meta‐analysis involving 511 AF patients (79% paroxysmal) with 263 catheter ablation (mean age 56 ± 3 years) and 248 surgical ablations (mean age 52 ± 4 years). Catheter ablation was associated with increased atrial arrhythmias recurrence when compared to surgical ablation (pooled relative risk = 1.85, 95% confidence interval: 1.44−2.39, p < .001, I2 = 0.0%) but associated with less total major adverse events (pooled relative risk = 0.29, 95% confidence interval: 0.16−0.53, p < .001, I2 = 0.0%). In subgroup analysis, catheter ablation was associated with increased AF recurrence in refractory paroxysmal AF when compared to surgical ablation (pooled relative risk = 2.47, 95% confidence interval: 1.31−4.65, p = .005, I2 = 0.0%) but not in persistent AF (relative risk = 1.09, 95% confidence interval: 0.60−2.0, p = .773).ConclusionCatheter ablation was associated with higher atrial arrhythmia recurrence when compared with surgical ablation. However, our study suggests that the benefit of surgical ablation in patients with persistent AF is unclear. More studies and alternative ablation strategies investigation in persistent AF are warranted.

Abstract Purpose: To identify molecular predictors of grade 3/4 neutropenic or leukopenic events (NLE) after chemotherapy using a genome-wide association study (GWAS). Experimental Design: A GWAS was performed on patients in the phase III chemotherapy study SUCCESS-A (n = 3,322). Genotyping was done using the Illumina HumanOmniExpress-12v1 array. Findings were functionally validated with cell culture models and the genotypes and gene expression of possible causative genes were correlated with clinical treatment response and prognostic outcomes. Results: One locus on chromosome 16 (rs4784750; NLRC5; P = 1.56E-8) and another locus on chromosome 13 (rs16972207; TNFSF13B; P = 3.42E-8) were identified at a genome-wide significance level. Functional validation revealed that expression of these two genes is altered by genotype-dependent and chemotherapy-dependent activity of two transcription factors. Genotypes also showed an association with disease-free survival in patients with an NLE. Conclusions: Two loci in NLRC5 and TNFSF13B are associated with NLEs. The involvement of the MHC I regulator NLRC5 implies the possible involvement of immuno-oncological pathways.