Citations

ObjectiveTo describe demographics and imaging and compare findings and symptoms at presentation in a large cohort of persons with cricopharyngeus muscle dysfunction (CPMD) with and without hypopharyngeal diverticula.MethodologyProspective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeal Hypertonicity (POUCH) Collaborative. Patient survey, comorbidities, radiography, laryngoscopy findings, and patient‐reported outcome measures (e.g., Eating Assessment Tool [EAT‐10]) data were abstracted from a REDCap database and summarized using means, medians, percentages, and frequencies. Diagnostic categories were compared using analysis of variance.ResultsA total of 250 persons were included. The mean age (standard deviation [SD]) of the cohort was 69.0 (11.2). Forty‐two percent identified as female. Zenker diverticula (ZD) was diagnosed in 85.2%, 9.2% with CPMD without diverticula, 4.4% with a Killian Jamieson diverticula (KJD), and 1.2% traction‐type diverticula. There were no differences between diagnostic categories in regard to age, gender, and duration of symptoms (p = 0.25, 0.19, 0.45). The mean (SD) EAT‐10 score for each group was 17.1 (10.1) for ZD, 20.2 (9.3) for CPMD, and 10.3 (9.4) for KJD. Patients with isolated CPMD had significantly greater EAT‐10 scores compared to the other diagnostic groups (p = 0.03).ConclusionZD is the most common, followed by CPMD without diverticula, KJD, and traction‐type. Patients with isolated obstructing CPMD may be more symptomatic than persons with ZD or KJD.Level of Evidence4 Laryngoscope, 133:1349–1355, 2023

Background TAILOR‐PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to decreased Clopidogrel Response After Percutaneous Coronary Intervention) studied genotype‐guided selection of antiplatelet therapy after percutaneous coronary intervention versus conventional therapy with clopidogrel. The presence of CYP2C19 loss‐of‐function alleles in patients treated with clopidogrel may be associated with increased risk for ischemic events. We report a prespecified sex‐specific analysis of genotyping and associated cardiovascular outcomes from this study. Methods and Results Associations between sex and major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia) and Bleeding Academic Research Consortium (BARC) bleeding at 12 months were analyzed using Cox proportional‐hazards models. Among 5276 randomized patients, loss‐of‐function carriers were observed in ≈36% of both sexes, and >80% of carriers were heterozygotes. At 12 months, after adjustment for baseline differences, risks of MACE (HR , 1.28 [0.97 to 1.68]; P =0.088) and BARC bleeding (hazard ratio [HR], 1.36 [0.91 to 2.05]; P =0.14) were comparable among women and men. There were no significant interactions between sex and treatment strategy for MACE interaction P value ( P int =0.59) or BARC bleeding ( P int =0.47) nor for sex and genotype (MACE P int =0.15, and BARC bleeding P int =0.60). Conclusions CYP2C19 loss‐of‐function alleles were present in ≈1 in 3 women and men. Women had similar adjusted risks of MACE and bleeding as men following percutaneous coronary intervention. Genotype‐guided therapy did not significantly reduce the risk of MACE or bleeding relative to conventional therapy for both sexes. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01742117.

ObjectiveThe aim of this study was to determine whether selection of treatment for children with infantile spasms (IS) varies by race/ethnicity.MethodsThe prospective US National Infantile Spasms Consortium database includes children with IS treated from 2012 to 2018. We examined the relationship between race/ethnicity and receipt of standard IS therapy (prednisolone, adrenocorticotropic hormone, vigabatrin), adjusting for demographic and clinical variables using logistic regression. Our primary outcome was treatment course, which considered therapy prescribed for the first and, when needed, the second IS treatment together.ResultsOf 555 children, 324 (58%) were non‐Hispanic white, 55 (10%) non‐Hispanic Black, 24 (4%) non‐Hispanic Asian, 80 (14%) Hispanic, and 72 (13%) other/unknown. Most (398, 72%) received a standard treatment course. Insurance type, geographic location, history of prematurity, prior seizures, developmental delay or regression, abnormal head circumference, hypsarrhythmia, and IS etiologies were associated with standard therapy. In adjusted models, non‐Hispanic Black children had lower odds of receiving a standard treatment course compared with non‐Hispanic white children (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.20–0.89; p = 0.02). Adjusted models also showed that children with public (vs. private) insurance had lower odds of receiving standard therapy for treatment 1 (OR, 0.42; CI, 0.21–0.84; p = 0.01).InterpretationNon‐Hispanic Black children were more often treated with non‐standard IS therapies than non‐Hispanic white children. Likewise, children with public (vs. private) insurance were less likely to receive standard therapies. Investigating drivers of inequities, and understanding the impact of racism on treatment decisions, are critical next steps to improve care for patients with IS. ANN NEUROL 2022;92:32–44

Background: Ischemic event rates are low after percutaneous coronary intervention (PCI), conversely second generation P2Y12 inhibitors increase bleeding therefore identifying patients at risk to enable precision in prescribing dual anti-platelet therapy (DAPT) is of clinical interest. Prior machine-learning predictive analyses have been limited by use of older generation stents and lack of genetic data. We utilized clinical and genetic data of patients with new generation stents enrolled in TAILOR-PCI, a 40-center international trial to predict ischemic events after PCI. Methods: There were 4398 eligible post PCI patients with acute coronary syndromes or stable coronary artery disease who were randomly split into training (n=3299) and validation (n=1099) cohorts. The primary endpoint comprising of cardiovascular death, myocardial infarction, stroke, or stent thrombosis within 12 months of PCI was predicted with patient characteristics prior to hospital discharge. First, random forests were used for feature selection with 1,000 bootstraps comprising equal numbers of those with and without ischemic events to minimize the bias of sample imbalance. Features were selected by a consensus on variable-importance over bootstraps. Second, using these features in the training cohort, support vector machines (SVM) with a polynomial kernel was trained with repeated 5-fold cross validation to choose a model with highest area under the receiver operating characteristic curve (AUC) which was then used to predict ischemic events in the validation cohort. Results: The primary endpoint occurred in 2.4% of patients. Using 89 clinical and genetic variables in the random-forest feature selection step, variable importance-based consensus identified 50 top predictors. These 50 predictors achieved AUC=0.703 in the SVM training cohort and AUC=0.744 (specificity=0.84; sensitivity =0.43) in the SVM validation cohort. Conclusions: Machine learning methods using baseline clinical and genetic data enables prediction of infrequent ischemic events in post PCI patients receiving new generation stents. The role of such artificial intelligence algorithms in individualization of DAPT by identifying high or low risk patients needs to be explored.

ABSTRACT Lipophagy is a central cellular process for providing the cell with a readily utilized, high energy source of neutral lipids. Since its discovery over a decade ago, we are just starting to understand the molecular components that drive lipophagy, how it is activated in response to nutrient availability, and its potential as a therapeutic target in disease. In this Cell Science at a Glance article and the accompanying poster, we first provide a brief overview of the different structural and enzymatic proteins that comprise the lipid droplet (LD) proteome and reside within the limiting phospholipid monolayer of this complex organelle. We then highlight key players in the catabolic breakdown of LDs during the functionally linked lipolysis and lipophagy processes. Finally, we discuss what is currently known about macro- and micro-lipophagy based on findings in yeast, mammalian and other model systems, and how impairment of these important functions can lead to disease states.

Energy Expenditure (EE) (kcal/day), a key element to guide obesity treatment, is measured from CO2 production, VCO2 (mL/min), and/or O2 consumption, VO2 (mL/min). Current technologies are limited due to the requirement of wearable facial accessories. A novel system, the Smart Pad, which measures EE via VCO2 from a room’s ambient CO2 concentration transients was evaluated. Resting EE (REE) and exercise VCO2 measurements were recorded using Smart Pad and a reference instrument to study measurement duration’s influence on accuracy. The Smart Pad displayed 90% accuracy (±1 SD) for 14–19 min of REE measurement and for 4.8–7.0 min of exercise, using known room’s air exchange rate. Additionally, the Smart Pad was validated measuring subjects with a wide range of body mass indexes (BMI = 18.8 to 31.4 kg/m2), successfully validating the system accuracy across REE’s measures of ~1200 to ~3000 kcal/day. Furthermore, high correlation between subjects’ VCO2 and λ for CO2 accumulation was observed (p < 0.00001, R = 0.785) in a 14.0 m3 sized room. This finding led to development of a new model for REE measurement from ambient CO2 without λ calibration using a reference instrument. The model correlated in nearly 100% agreement with reference instrument measures (y = 1.06x, R = 0.937) using an independent dataset (N = 56).

Background In TAILOR‐PCI, genotype‐guided selection of P2Y 12 inhibitors after percutaneous coronary intervention did not significantly reduce the risk of ischemic events at 12 months. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD‐GENE) score identifies patients with high platelet reactivity on clopidogrel at increased risk of ischemic events. The aim of this study was to investigate the value of the ABCD‐GENE score for tailoring P2Y 12 inhibitor selection after percutaneous coronary intervention. Methods and Results In a post hoc analysis of the TAILOR‐PCI, outcomes were analyzed by ABCD‐GENE score and allocation to genotype‐guided or conventional P2Y 12 inhibitor selection. Primary (death, myocardial infarction, or stroke) and secondary (cardiovascular death, myocardial infarction, stroke, stent thrombosis, or severe recurrent ischemia) outcomes were assessed. Among 3883 patients discharged on clopidogrel in the genotype‐guided and conventional therapy groups, 15.8% and 84.2% had high (≥10 points) or low (<10) ABCD‐GENE scores, respectively. At 12 months, both the primary (5.2% versus 2.6%, P <0.001) and secondary outcomes (7.7% versus 4.6%, P =0.001) were significantly increased in patients with high ABCD‐GENE score. Among 4714 patients allocated to genotype‐guided or conventional therapy, the former did not significantly reduce the 12‐month risk of the primary and secondary outcomes in both the high and low ABCD‐GENE score groups (p interaction =0.48 and 0.27, respectively). Conclusions Among patients with percutaneous coronary intervention on clopidogrel, the ABCD‐GENE score was helpful in identifying those at higher risk. The ABCD‐GENE score may potentially enhance the precision of tailored selection of P2Y 12 inhibitors, which needs to be confirmed in prospective investigations. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique Identifier: NCT01742117.

Abstract Autoimmune polyglandular syndromes (APS) are rare disorders characterized by auto‐destruction of endocrine and non‐endocrine organs by organ‐specific antibody‐directed T‐lymphocytic infiltration. This case highlights a 29‐year‐old Caucasian man with vitiligo found to have significant neurological abnormalities in the setting of newly diagnosed pernicious anemia and thyroid autoimmune disease.