Citations

Abstract Subclavian steal syndrome (SSS) is a rare vascular condition characterized by retrograde blood flow in the vertebral artery, often discovered incidentally in asymptomatic patients. We present a 65-year-old male with recurrent transient ischemic attacks (TIAs) attributed to 99% stenosis at the origin of the left subclavian artery, leading to SSS. Diagnostic modalities included duplex ultrasound, confirming inverted left vertebral artery flow, and multi-slice computed tomography angiography, confirming the diagnosis. Despite an unsuccessful attempt at balloon angioplasty, successful vascular surgery was performed, establishing a left carotid-vertebral artery bypass. The patient recovered well without complications. This case underscores the importance of considering SSS in TIA cases, utilizing non-invasive diagnostic tools, and highlighting the successful management of symptomatic SSS through surgical intervention.

OBJECTIVE This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. METHODS A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. RESULTS The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19–0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25–0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38–10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26–8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04–0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48–230, p = 0.024). CONCLUSIONS The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.

BACKGROUND: There has been concern among colon and rectal surgery residency programs in the United States that IPAA procedures have been decreasing, but evidence is limited. OBJECTIVE: The study aimed to evaluate the number of IPAAs performed by colon and rectal surgery residents in the United States and analyze the distribution of these cases on a national level. DESIGN: Retrospective. SETTINGS: The Accreditation Council for Graduate Medical Education Case Log National Data Reports were used to evaluate the number of IPAAs performed by residents from 2005 to 2021. The Nationwide Inpatient Sample database was used to identify all patients undergoing these procedures from 2005 to 2019. PATIENTS: All IPAA procedures regardless of indication. MAIN OUTCOME MEASURES: The primary outcome was the number of IPAAs performed by residents yearly. The secondary outcome was the national distribution of these procedures. RESULTS: Among colon and rectal surgery residents, case log data revealed an increase in mean and total number of IPAAs from 2005 to 2013, followed by a decline in both metrics after 2013. Despite the decrease, the mean number of cases per resident remained fewer than 6 between 2011 and 2021. A weighted national estimate of 48,532 IPAA patients were identified in the Nationwide Inpatient Sample database. A significant decrease was noted in the number of IPAAs after 2015 that persisted through 2019. There was a significant decrease in rural and urban nonteaching hospitals (from 2.1% to 1.6% and 25.6% to 4.3%, respectively; p < 0.001) and an increase in urbanteaching hospitals (from 72.4% to 94.1%; p < 0.001). LIMITATIONS: Nonrandomized retrospective study design. CONCLUSIONS: Despite the recent increase in the percentage of IPAAs performed at urban academic centers, there has been a decrease in cases performed by colon and rectal surgery residents. This can have significant implications for residents who graduate without adequate experience in performing this complex procedure independently, as well as training programs that may face challenges with maintaining accreditation. See Video Abstract. TENDENCIAS Y DISTRIBUCIÓN DE LA ANASTOMOSIS ANAL CON BOLSA ILEAL EN LOS ESTADOS UNIDOS: ¿SE ESTÁ VOLVIENDO MÁS DIFÍCIL DE ENCONTRAR EN LA CAPACITACIÓN DE RESIDENCIA EN CIRUGÍA DE COLON Y RECTO? ANTECEDENTES: Ha habido preocupación entre los programas de capacitación de residencia en cirugía de colon y recto en los Estados Unidos porque los procedimientos de anastomosis anal con bolsa ileal han estado disminuyendo; sin embargo, la evidencia es limitada. OBJETIVO: Evaluar el número de anastomosis anales con bolsa ileal realizadas por residentes de cirugía de colon y recto en los Estados Unidos y examinar la distribución de estos casos a nivel nacional. DISEÑO: Retrospectivo. AJUSTES: Se utilizaron los informes de datos nacionales del registro de casos de educación médica de posgrado del Consejo de Acreditación para examinar el número de anastomosis anales con bolsa ileal realizadas por residentes de 2005 a 2021. Se utilizó la base de datos de muestra nacional de pacientes hospitalizados para identificar a todos los pacientes sometidos a estos procedimientos de 2005 a 2019. PACIENTES: Todos los procedimientos de anastomosis anal con bolsa ileal independientemente de la indicación. MEDIDA DE RESULTADO PRINCIPAL: El resultado primario es el número de anastomosis anales con bolsa ileal realizadas por los residentes anualmente. El resultado secundario es la distribución nacional de estos procedimientos. RESULTADOS: Entre los residentes de cirugía de colon y recto, los datos de los registros de casos revelaron un aumento en el número medio y total de anastomosis anal con bolsa ileal de 2005 a 2013, seguido de una disminución en ambas métricas después de 2013. A pesar de la disminución, el número medio de casos por El residente permaneció >6 entre 2011 y 2021. Se identificó una estimación nacional ponderada de 48 532 pacientes con anastomosis anal con bolsa ileal en la base de datos de la Muestra Nacional de Pacientes Hospitalizados. Se observó una disminución significativa en el número de anastomosis anales con bolsa ileal después de 2015 que persistió hasta 2019. Hubo una disminución significativa en los hospitales no docentes rurales y urbanos (del 2,1% al 1,6% y del 25,6% al 4,3% respectivamente, p < 0,001) y un aumento en los hospitales universitarios urbanos (del 72,4% al 94,1%, p < 0,001). LIMITACIONES: Estudio retrospectivo no aleatorizado. CONCLUSIÓN: A pesar del reciente aumento en el porcentaje de anastomosis anal con bolsa ileal realizadas en centros académicos urbanos, ha habido una disminución en los casos realizados por residentes de cirugía de colon y recto. Esto puede tener implicaciones significativas para los residentes que se gradúan sin la experiencia adecuada en la realización de este complejo procedimiento de forma independiente, así como para los programas de capacitación que pueden enfrentar desafíos para mantener la acreditación. (Traduccion—AI-generated)

Abstract Rearrangements that place the oncogenes MYC, BCL2, or BCL6 adjacent to superenhancers are common in mature B-cell lymphomas. Lymphomas with diffuse large B-cell lymphoma (DLBCL) or high-grade morphology with both MYC and BCL2 rearrangements are classified as high-grade B-cell lymphoma with MYC and BCL2 rearrangements (“double hit”; HGBCL-DH-BCL2) and are associated with aggressive disease and poor outcomes. Although it is established that MYC rearrangements involving immunoglobulin (IG) loci are associated with inferior outcomes relative to those involving other non-IG superenhancers, the frequency of and mechanisms driving IG vs non-IG MYC rearrangements have not been elucidated. Here, we used custom targeted capture and/or whole-genome sequencing to characterize oncogene rearrangements across 883 mature B-cell lymphomas including Burkitt lymphoma, follicular lymphoma, DLBCL, and HGBCL-DH-BCL2 tumors. We demonstrate that, although BCL2 rearrangement topology is consistent across entities, HGBCL-DH-BCL2 have distinct MYC rearrangement architecture relative to tumors with single MYC rearrangements or with both MYC and BCL6 rearrangements (HGBCL-DH-BCL6), including both a higher frequency of non-IG rearrangements and different architecture of MYC::IGH rearrangements. The distinct MYC rearrangement patterns in HGBCL-DH-BCL2 occur on the background of high levels of somatic hypermutation across MYC partner loci in HGBCL-DH-BCL2, creating more opportunity to form these rearrangements. Furthermore, because 1 IGH allele is already disrupted by the existing BCL2 rearrangement, the MYC rearrangement architecture in HGBCL-DH-BCL2 likely reflects selective pressure to preserve both BCL2 and B-cell receptor expression. These data provide new mechanistic explanations for the distinct patterns of MYC rearrangements observed across different lymphoma entities.

PURPOSE The emergence of large real-world clinical databases and tools to mine electronic medical records has allowed for an unprecedented look at large data sets with clinical and epidemiologic correlates. In clinical cancer genetics, real-world databases allow for the investigation of prevalence and effectiveness of prevention strategies and targeted treatments and for the identification of barriers to better outcomes. However, real-world data sets have inherent biases and problems (eg, selection bias, incomplete data, measurement error) that may hamper adequate analysis and affect statistical power. METHODS Here, we leverage a real-world clinical data set from a large health network for patients with breast cancer tested for variants in BRCA1 and BRCA2 (N = 12,423). We conducted data cleaning and harmonization, cross-referenced with publicly available databases, performed variant reassessment and functional assays, and used functional data to inform a variant's clinical significance applying American College of Medical Geneticists and the Association of Molecular Pathology guidelines. RESULTS In the cohort, White and Black patients were over-represented, whereas non-White Hispanic and Asian patients were under-represented. Incorrect or missing variant designations were the most significant contributor to data loss. While manual curation corrected many incorrect designations, a sizable fraction of patient carriers remained with incorrect or missing variant designations. Despite the large number of patients with clinical significance not reported, original reported clinical significance assessments were accurate. Reassessment of variants in which clinical significance was not reported led to a marked improvement in data quality. CONCLUSION We identify the most common issues with BRCA1 and BRCA2 testing data entry and suggest approaches to minimize data loss and keep interpretation of clinical significance of variants up to date.

Abstract Context Single-tier newborn screening (NBS) for congenital adrenal hyperplasia (CAH) using 17-hydroxyprogesterone (17OHP) measured by fluoroimmunoassay (FIA) in samples collected at 24 to 48 hours produces a high false-positive rate (FPR). Second-tier steroid testing can reduce the FPR and has been widely implemented. Objective We investigated the accuracy of an alternative multitier CAH NBS protocol that incorporates molecular testing of the CYP21A2 gene and reduces the first-tier 17OHP cutoff to minimize missed cases. Methods We create a Minnesota-specific CYP21A2 pathogenic variants panel; developed a rapid, high-throughput multiplex, allele-specific-primer-extension assay; and performed a 1-year retrospective analysis of Minnesota NBS results comparing metrics between a conventional steroid-based 2-tier protocol and a molecular-based multitier NBS protocol, applied post hoc. Results CYP21A2 gene sequencing of 103 Minnesota families resulted in a Minnesota-specific panel of 21 pathogenic variants. The Centers for Disease Control and Prevention created a molecular assay with 100% accuracy and reproducibility. Two-tier steroid-based screening of 68 659 live births during 2015 resulted in 2 false negatives (FNs), 91 FPs, and 1 true positive (TP). A 3-tier protocol with a lower first-tier steroid cutoff, second-tier 21-variant CYP21A2 panel, and third-tier CYP21A2 sequencing would have resulted in 0 FNs, 52 FPs, and 3 TPs. Conclusion Incorporation of molecular testing could improve the accuracy of CAH NBS, although some distinct challenges of molecular testing may need to be considered before implementation by NBS programs.

Abstract Approximately 5% of Alzheimer’s disease patients develop symptoms before age 65 (early-onset Alzheimer’s disease), with either sporadic (sporadic early-onset Alzheimer’s disease) or dominantly inherited (dominantly inherited Alzheimer’s disease) presentations. Both sporadic early-onset Alzheimer’s disease and dominantly inherited Alzheimer’s disease are characterized by brain amyloid-β accumulation, tau tangles, hypometabolism and neurodegeneration, but differences in topography and magnitude of these pathological changes are not fully elucidated. In this study, we directly compared patterns of amyloid-β plaque deposition and glucose hypometabolism in sporadic early-onset Alzheimer’s disease and dominantly inherited Alzheimer’s disease individuals. Our analysis included 134 symptomatic sporadic early-onset Alzheimer’s disease amyloid-Positron Emission Tomography (PET)-positive cases from the University of California, San Francisco, Alzheimer’s Disease Research Center (mean ± SD age 59.7 ± 5.6 years), 89 symptomatic dominantly inherited Alzheimer’s disease cases (age 45.8 ± 9.3 years) and 102 cognitively unimpaired non-mutation carriers from the Dominantly Inherited Alzheimer Network study (age 44.9 ± 9.2). Each group underwent clinical and cognitive examinations, 11C-labelled Pittsburgh Compound B-PET and structural MRI. 18F-Fluorodeoxyglucose-PET was also available for most participants. Positron Emission Tomography scans from both studies were uniformly processed to obtain a standardized uptake value ratio (PIB50–70 cerebellar grey reference and FDG30–60 pons reference) images. Statistical analyses included pairwise global and voxelwise group comparisons and group-independent component analyses. Analyses were performed also adjusting for covariates including age, sex, Mini-Mental State Examination, apolipoprotein ε4 status and average composite cortical of standardized uptake value ratio. Compared with dominantly inherited Alzheimer’s disease, sporadic early-onset Alzheimer’s disease participants were older at age of onset (mean ± SD, 54.8 ± 8.2 versus 41.9 ± 8.2, Cohen’s d = 1.91), with more years of education (16.4 ± 2.8 versus 13.5 ± 3.2, d = 1) and more likely to be apolipoprotein ε4 carriers (54.6% ε4 versus 28.1%, Cramer’s V = 0.26), but similar Mini-Mental State Examination (20.6 ± 6.1 versus 21.2 ± 7.4, d = 0.08). Sporadic early-onset Alzheimer’s disease had higher global cortical Pittsburgh Compound B-PET binding (mean ± SD standardized uptake value ratio, 1.92 ± 0.29 versus 1.58 ± 0.44, d = 0.96) and greater global cortical 18F-fluorodeoxyglucose-PET hypometabolism (mean ± SD standardized uptake value ratio, 1.32 ± 0.1 versus 1.39 ± 0.19, d = 0.48) compared with dominantly inherited Alzheimer’s disease. Fully adjusted comparisons demonstrated relatively higher Pittsburgh Compound B-PET standardized uptake value ratio in the medial occipital, thalami, basal ganglia and medial/dorsal frontal regions in dominantly inherited Alzheimer’s disease versus sporadic early-onset Alzheimer’s disease. Sporadic early-onset Alzheimer’s disease showed relatively greater 18F-fluorodeoxyglucose-PET hypometabolism in Alzheimer’s disease signature temporoparietal regions and caudate nuclei, whereas dominantly inherited Alzheimer’s disease showed relatively greater hypometabolism in frontal white matter and pericentral regions. Independent component analyses largely replicated these findings by highlighting common and unique Pittsburgh Compound B-PET and 18F-fluorodeoxyglucose-PET binding patterns. In summary, our findings suggest both common and distinct patterns of amyloid and glucose hypometabolism in sporadic and dominantly inherited early-onset Alzheimer’s disease.

Abstract Background: Flash glucose monitoring (FGM) can improve diabetes management, but no randomised controlled trials (RCTs) of FGM have been undertaken in Indigenous Australian populations. This study aimed to assess the feasibility of performing a RCT of FGM in Indigenous Australians with type 2 diabetes. Methods: In this open-labelled pilot RCT, Indigenous adults with type 2 diabetes were randomised to FGM or standard care for 6 months. Eligible participants were being treated with injectable diabetes medications and had a glycosylated haemoglobin (HbA1c) ≥ 7.0%. The feasibility outcome was the proportion of participants completing the trial. The preliminary effective outcome was the change in HbA1c. Secondary effectiveness outcomes included a change in time spent in target blood glucose; safety (hypoglycaemic episodes); and quality of life (EuroQol 5-Dimension 3-Level (EQ-5D-3L) score). Results: Of 126 screened individuals, 74 were eligible, 40 (31.7%) were randomised and 39 (97.5%) completed the study. Participants’ baseline characteristics were similar between the FGM and usual care groups, except for sex and body mass index. There were no between-group differences for: change in HbA1c; percentage of time spent in target blood glucose, low glucose and high glucose; or EQ-5D-3L scores. No severe hypoglycaemic episodes occurred. Conclusions: This is the first pilot RCT of FGM in Indigenous Australians with type 2 diabetes. The results support a larger RCT, which is currently in progress. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR12621000021875), retrospectively registered on 14 January 2021.