Citations

Summary: Facial synkinesis manifests as involuntary muscle movements alongside volitional facial actions and is typically managed with a combination of neuromuscular retraining, botulinum toxin injections, and in some cases, selective neurectomy. Some patients with synkinesis describe persistent neck tightness or pain at the level of the mandibular angle and horizontally towards the midline, similar to the anatomic course of the posterior belly of digastric (PBD) and stylohyoid muscles. There are limited studies exploring the involvement of the PBD and stylohyoid muscles in facial synkinesis and the use of chemodenervation as treatment. Herein, we present 2 patients with facial synkinesis and ipsilateral neck tightness and pain who underwent novel surgical treatment in the form of the standard selective neurectomy procedure along with a myectomy of the PBD and stylohyoid muscles. Following completion of the standard steps of selective neurectomy, the PBD and stylohyoid muscles were carefully dissected and separated from the surrounding structures. Both muscles were divided using bipolar electrocautery. Both patients reported improvement of neck pain and tightness immediately after the intervention and at the 6.5-month follow-up visit. These preliminary results show promise in aiding a subset of patients with synkinesis-related neck pain and tightness.

Abstract Background and aims This post hoc analysis evaluated the corticosteroid-sparing effects of risankizumab (RZB) therapy in patients with moderate-to-severe ulcerative colitis in the phase 3 induction and maintenance studies, INSPIRE and COMMAND. Methods Patients were randomized (2:1) to 12 weeks of intravenous RZB or placebo (PBO) induction therapy; responders to intravenous RZB were randomized (1:1:1) to receive subcutaneous RZB 180 mg, 360 mg, or PBO (RZB withdrawal) maintenance therapy. Baseline corticosteroid doses were maintained during induction, with a mandatory taper beginning at maintenance week 0. Efficacy outcomes were evaluated by baseline corticosteroid use at induction week 12, while corticosteroid-free clinical and endoscopic outcomes were assessed at maintenance week 52 among the overall population and among patients on corticosteroids at baseline. Safety was also assessed. Results At baseline, 35.7% (348/975) of patients were taking corticosteroids. At induction week 12, greater rates were observed for clinical, endoscopic, and patient-reported outcomes in RZB 1200 mg-treated patients compared with PBO, regardless of baseline corticosteroid use. RZB 180 mg and 360 mg treatment resulted in higher corticosteroid discontinuation rates (RZB 180 mg 64.9% [48/74]; RZB 360 mg 54.2% [32/59]; PBO [withdrawal] 36.8% [25/68], P ≤ .01) and corticosteroid-free clinical, endoscopic, and patient-reported outcomes at week 52, compared with PBO (withdrawal). The rates of treatment-emergent adverse events were similar regardless of baseline corticosteroid use during induction and maintenance. Conclusions The efficacy of RZB induction therapy was independent of corticosteroid use, with high rates of corticosteroid-free outcomes observed in the overall population and among patients with baseline corticosteroid use, reaffirming the potential of RZB to serve as a corticosteroid-sparing therapy for patients with ulcerative colitis. Clinicaltrial.gov numbers NCT03398148 and NCT03398135

Abstract The pharmacological provocation test is a pivotal tool in cardiac electrophysiology for the diagnosis of potential causes of sudden cardiac death, sudden cardiac arrest (SCA), arrhythmias, symptoms, or ECG abnormalities. The 2022 European Society of Cardiology Guidelines for the Treatment of Ventricular Arrhythmias and Prevention of Sudden Cardiac Death offered guidance on provocation testing but did not describe the indications and requirements in depth. This clinical consensus statement, led by the European Heart Rhythm Association and approved by major international stakeholders, aims to advise the general cardiologist and the arrhythmia expert who to test and when, where, and how to do it. The statement focuses on current practice for the diagnosis of subclinical arrhythmia syndromes and the causes of SCA, building upon the recommendations of the Guidelines. We address the sodium channel blocker provocation test for patients suspected of Brugada syndrome as well as the use of epinephrine, isoproterenol, adenosine, ergonovine, and acetylcholine.

BACKGROUND AND OBJECTIVES: Rising US healthcare costs and the COVID-19 pandemic put increased pressure on hospitals to reduce patient length of stay (LOS) while maintaining high-quality care. We aimed to determine if implementing a pathway for same-day discharge after elective neuroendovascular procedures to a monitored hotel setting is safe, feasible, and cost-effective. METHODS: We evaluated patient outcomes after elective neuroendovascular procedures and same-day discharge to an on-campus Care Hotel. The study enrolled patients aged ≥18 years from October 1, 2020, to February 28, 2023. Exclusion criteria comprised major comorbidities, additional care necessitating hospitalization, absence of a caregiver, insurer-mandated hospitalization, or patient refusal of the Care Hotel model. Primary outcomes were readmission rate or prolonged LOS, new ischemic or hemorrhagic complications rate, and death rate from vascular causes within 6 months. Secondary outcomes included adverse events and deaths related to causes other than vascular complications within 6 months and changes in modified Rankin Scale score by 1 or more points at last follow-up. Healthcare cost savings associated with same-day discharge were analyzed using a control group. RESULTS: The study included 42 patients discharged to the Care Hotel and 84 controls. The average age was 61 years in the Care Hotel group and 64 years in the control group, and aneurysm treatment was the most frequent neuroendovascular procedure (83.3% and 79.8%, respectively). The readmission and extended LOS rates were 4.8% for the Care Hotel group. The rate of new ischemic or hemorrhagic complications was 4.8%. Cost analysis estimated savings of $7730.12 per procedure. CONCLUSION: This study suggests that the Care Hotel model is a safe, feasible, and cost-effective option for carefully selected patients undergoing elective neuroendovascular interventions. Adherence to discharge readiness criteria and meticulous patient selection are critical to minimizing complications and readmissions.

Abstract The advent of high-throughput sequencing has led to an exponential increase in genomic data, highlighting the need for efficient and accurate models to analyze and interpret this information. Here, we introduce a novel, exomic foundational model that leverages a combination of human reference genome and multispecies data to improve variant detection and interpretation. Our model utilizes a short- range transformer architecture and is trained on a large dataset of human exomic sequences derived from the Tapestry study. Through a series of ablation studies and scaling experiments, we demonstrate the effectiveness of our model in pre- dicting next token accuracy and identifying clinically pathogenic variants. We also show that our model outperforms existing models in a range of downstream tasks, including variant effect prediction and disease state identification. In fact, our largest STRAND variant (1B parameters) surpassed previous benchmarks, demonstrating a mean accuarcy of 0.880 (8.2% improvement over the original NT and 7% improvement over NT-v2). Furthermore, we construct a unique exomic ClinVar dataset to evaluate the model’s performance on pathogenicity and disease states. Our results highlight the potential of this model to improve our understanding of the human exome and its role in disease. The model and its applications have significant implications for genomic based diagnosis and personalized medicine including tailored therapeutic development.

AbstractDespite the pivotal role of communication skills in genetic counseling, communication strategies employed by genetic counselors in their current practice remain largely unexplored. The field of genetic counseling could benefit from updated simulated genetic counseling sessions conducted by genetic counselors illustrating a diversity of skills. This paper outlines the development and evaluation of updated simulations used to develop an online training course to identify genetic counseling skills and to assess how commonly these skills are used. Practicing genetic counselors in the United States were recruited to counsel trained standardized patients across six pretest and posttest simulated sessions in cancer, prenatal, and cardiology genetics settings. Sessions were coded using the novel Genetic Counseling Skills Checklist to identify which communication and counseling skills were utilized. Standardized patients were asked to provide session quality ratings and written feedback, which were analyzed using descriptive statistics and content analysis, respectively. Results from 64 recorded sessions involving 20 counselors from a variety of training programs, racial and ethnic backgrounds, states of residence, and with varying years of clinical experience revealed utilization of a broad array of skills across specialty types and clinical indications. The total number of unique skills used varied widely from 12 to 49, with an average of 35.8 out of 56 possible skills checked per session. Differences in skill usage were observed between pretest and posttest sessions. Standardized patient comments were predominantly positive with a focus on information delivery and empathetic responses. Perceptions of areas of improvement were giving less information, having clearer delivery, and expressing more empathy. This work led to the creation of a training course showcasing various skills used by practicing genetic counselors, which summarizes commonly used skills and other promising but less frequently utilized ones.

Abstract Objective Biallelic pathogenic MBOAT7 variants are associated with neurodevelopmental disorders, intellectual disability (ID), epilepsy, and neuropsychiatric disorders such as attention‐deficit/hyperactivity disorder and autism spectrum disorders. We aimed to characterize the epilepsy phenotype in a cohort of patients affected by this syndrome. Methods We describe epilepsy features, electroencephalography, magnetic resonance imaging (MRI) findings, antiseizure treatment response, and neurodevelopment of 15 patients with biallelic MBOAT7 variants. Results All 15 patients had ID or developmental delay (DD). Twelve suffered from epilepsy, with mean age at seizure onset of 36 months (range = 2 months–6.5 years) and 10 of 12 showing signs of DD before seizure onset. Patients with epilepsy presented with focal motor seizures with impaired awareness ( n = 3), focal tonic–clonic seizures and epileptic spasms ( n = 1), focal to bilateral tonic–clonic seizures ( n = 1), unknown onset bilateral tonic–clonic seizures ( n = 2), myoclonic seizures ( n = 4), myoclonic–atonic seizures ( n = 1), atonic seizures ( n = 1), tonic seizures ( n = 1), and myoclonic absences ( n = 2). Seizure freedom was achieved in 66.7% (8/12), with variable antiseizure treatment regimes. We reviewed electroencephalograms of the patients with epilepsy. Background activity was normal in 64%, whereas 36% had either a generalized or a focal slowing. Interictal epileptiform discharges (IEDs) were reported in 83%. Generalized spikes/polyspikes were found in 53%, multifocal IEDs in 23%, and parasagittal focal IEDs in 26%. The most frequent abnormal brain MRI findings, reported in 58% of patients, included high‐intensity signal in T2 and fluid‐attenuated inversion recovery (FLAIR) sequences in dentate nuclei and globus pallidus. Biallelic missense variants seemed to be associated with better cognitive and motor outcomes compared to truncating variants and in‐frame deletions. Significance Biallelic MBOAT7 variants are associated with global developmental impairment in all affected patients and epilepsy in the majority. The seizure semiology is heterogenous. One third of our cohort had persistent seizures despite treatment. The most frequent MRI findings were hyperintensities in T2/FLAIR sequences in dentate nuclei and globus pallidus.

Abstract Objective Dravet syndrome (DS) is a developmental and epileptic encephalopathy. Diagnosis is clinical, but ~90% of patients have pathogenic variants in SCN1A . ATP6V0C has recently been proposed as a novel candidate gene for epilepsy, with or without developmental delay. Here we describe two adult patients with a clinical diagnosis of DS associated with ATP6V0C variants. Methods Patients with developmental and epileptic encephalopathies were evaluated by physicians who are experts in DS, and their clinical diagnosis was correlated with genetic findings. A subgroup of those patients with DS but without known genetic causes were evaluated through gene panels, whole exome sequencing, and chromosome microarray. Phenotype was determined by pediatric and adult chart reviews, interviews, and physical examinations. Results Of 753 patients with DS, two unrelated individuals with classic features of DS during childhood and adulthood were identified with heterozygous de novo missense variants in ATP6V0C (c.319G > C, p.(Gly107Arg) and c.284C > T, p.(Ala95Val), respectively). Both variants were absent in normal populations and computational prediction algorithms suggested deleterious effects on protein structure and/or function. No disease‐causing variants in other genes previously associated with DS were found. Significance Here we describe two adult patients with Dravet‐like syndrome and pathogenic/likely pathogenic variants in ATP6V0C . We propose that abnormal ATP6V0C function can, at the severe end of the clinical spectrum, be associated with Dravet‐like phenotype. This is relevant, as these patients would not qualify for disease‐modifying antisense nucleotide or gene therapies targeting SCN1A .

ABSTRACTIntroductionVaccination is crucial to the thoracic solid organ transplant (SOT) population to reduce vaccine‐preventable infection. However, data on posttransplant hepatitis B virus (HBV) vaccination compliance and vaccine‐induced seroprotection are lacking.MethodsWe conducted a retrospective study of adult thoracic organ (heart and lung) transplant recipients at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2018 and August 2023. Recombivax HB was used before 2020, and Heplisav‐B was preferred after 2020. Recipients with posttransplant hepatitis B surface antibody (HBsAb) < 10 IU/L were eligible for the HBV vaccine. HBV seroprotection was defined as an HBsAb ≥ 10 IU/L.ResultsA total of 1116 recipients were evaluated, all of whom underwent posttransplant HBsAb testing. Of these, 751 (67%) had an HBsAb level < 10 IU/L and were eligible for posttransplant HBV vaccination. Of the eligible recipients, 117 (16%) completed the HBV vaccine series during the study period. Among these 117 recipients, 40 (34%) had their HBsAb levels rechecked after completing the vaccine series, with a seroprotection rate of 37.5% (15/40). There was no statistically significant difference in the seroprotection rates between Heplisav‐B and Recombivax HB vaccines (39% [13/33] vs. 29% [2/7]; p = 0.691). In addition, HBsAb levels were lowest at week 2 but rebounded at week 4 posttransplant and pretransplant HBsAb levels of ≥100 IU/L ensured 5‐year seroprotection.ConclusionSuboptimal compliance with HBV vaccination and poor vaccine‐induced seroprotection occur in thoracic organ transplant recipients, regardless of the vaccine used. These findings underscore the necessity of enhancing vaccination strategies for SOT recipients. image

Abstract Based on expert consensus, the American Society of Transplantation recommends 7–14 days of preventive antibiotic therapy for solid organ transplant recipients from donors with positive blood cultures. We evaluated management and outcomes of kidney transplant recipients from these donors.