Improving Completion Rates of Transcranial Doppler Ultrasounds in Children With Sickle Cell Disease Using Quality Improvement Efforts: In-Clinic versus Population-Based Assessments.

Transcranial Doppler (TCD) screening is essential for stroke prevention in children with sickle cell disease (SCD), but screening rates are low nationally. We use Medicaid administrative claims to assess TCD completion rates before and after a 12-month QI initiative to improve rates in the Pacific Sickle Cell Regional Collaborative (PSCRC). We found an increase in TCD screening rates for QI participant sites (52.

Type 2 diabetes mellitus: A cross-sectional analysis of glycemic controls and brain health outcomes.

In this cross-sectional analysis, we explored how fluctuations in glycemic levels impact executive functions and psychosocial outcomes in patients with type 2 diabetes mellitus (T2DM). The goal was to understand the relationship between glycemic control and both neuropsychological and psychosocial health. We stratified participants into well-controlled and poorly controlled groups based on glycated hemoglobin (HbA1c) levels and variability, including a healthy control group for comparison.

Coaching for improving clinical performance of surgeons: a scoping review.

Surgical coaching has been proven to effectively enhance clinical performance. However, diverse implementation strategies present challenges when initiating new programs. Our scoping review aimed to synthesize the existing literature on surgical coaching, thereby informing the direction of future coaching initiatives.

An orally available P1'-5-fluorinated M inhibitor blocks SARS-CoV-2 replication without booster and exhibits high genetic barrier.

We identified a 5-fluoro-benzothiazole-containing small molecule, TKB272, through fluorine-scanning of the benzothiazole moiety, which more potently inhibits the enzymatic activity of SARS-CoV-2's main protease (M) and more effectively blocks the infectivity and replication of all SARS-CoV-2 strains examined including Omicron variants such as SARS-CoV-2 and SARS-CoV-2 than two M inhibitors: nirmatrelvir and ensitrelvir. Notably, the administration of ritonavir-boosted nirmatrelvir and ensitrelvir causes drug-drug interactions warranting cautions due to their CYP3A4 inhibition, thereby limiting their clinical utility. When orally administered, TKB272 blocked SARS-CoV-2 replication without ritonavir in B6.

Consortium-driven rapid software validation for Research Electronic Data Capture (REDCap).

There is a growing trend for studies run by academic and nonprofit organizations to have regulatory submission requirements. As a result, there is greater reliance on REDCap, an electronic data capture (EDC) widely used by researchers in these organizations. This paper discusses the development and implementation of the Rapid Validation Process (RVP) developed by the REDCap Consortium, aimed at enhancing regulatory compliance and operational efficiency in response to the dynamic demands of modern clinical research.

Evaluating the association of genotype and cognitive resilience in SuperAgers.

Importance: "SuperAgers" are oldest-old adults (ages 80+) whose memory performance resembles that of adults in their 50s to mid-60s. Factors underlying their exemplary memory are underexplored in large, racially diverse cohorts.

Objective: To determine the frequency of genotypes in non-Hispanic Black and non-Hispanic White SuperAgers compared to middle-aged (ages 50-64), old (ages 65-79), and oldest-old (ages 80+) controls and Alzheimer's disease (AD) dementia cases.

Predilection for Perplexion: Preoperative microstructural damage is linked to postoperative delirium.

Postoperative delirium is the most common postsurgical complication in older adults and is associated with an increased risk of long-term cognitive decline and Alzheimer's disease (AD) and related dementias (ADRD). However, the neurological basis of this increased risk-whether postoperative delirium unmasks latent preoperative pathology or leads to AD-relevant pathology after perioperative brain injury-remains unclear. Recent advancements in neuroimaging techniques now enable the detection of subtle brain features or damage that may underlie clinical symptoms.

Assessment and treatment considerations for patients with colorectal liver metastases: AHPBA consensus guideline and update for surgeons.

Background: Colorectal cancer most commonly metastasizes to the liver. While various treatment strategies have been developed, surgical management of these patients has vital implications on the prognosis and survival of this group of patients. There remains a need for a consensus guideline regarding the surgical evaluation and management of patients with colorectal liver metastases (CRLM).

MAPPING THE CEREBROSPINAL FLUID PROTEOME IN BIPOLAR DISORDER.

Background: Bipolar disorder (BD) is a severe psychiatric condition with unclear etiology and no established biomarkers. Here, we aimed to characterize the cerebrospinal fluid (CSF) proteome in euthymic BD individuals to identify potential protein biomarkers.

Methods: We employed nano-flow liquid chromatography coupled to high-resolution mass spectrometry to quantify over 2,000 CSF proteins in 374 individuals from two independent clinical cohorts (n=164+89 and 66+55 cases and controls, respectively).

The ACTION VAD registry: A collective five-year experience.

Background: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) began in 2018 as a collaborative learning health system committed to improving outcomes in pediatric heart failure, including children and adults with congenital heart disease, supported with ventricular assist devices (VADs). This report describes patient and device characteristics, and outcomes through 1-year post-implant.

Methods: The ACTION VAD registry report was created from data submitted to the ACTION learning network from April 2018 to June 2023.

Novel synaptic markers predict early tau pathology and cognitive deficit in an asymptomatic population at risk of Alzheimer's disease.

Cognitive dysfunction in Alzheimer's disease (AD) correlates closely with pathology in the neuronal microtubule-associated protein tau. Tau pathology may spread via neural synapses. In a population of cognitively unimpaired elderly at elevated risk of AD, we investigated four cerebrospinal (CSF) markers of synaptic dysfunction and degeneration.

Identification of MORF4L1 as an endogenous substrate of CRBN and its potential role as a therapeutic target in cancer.

The ubiquitin-proteasome system (UPS) is essential for cellular homeostasis, regulating the degradation of proteins involved in key processes such as cell cycle, apoptosis, and DNA repair. Dysregulation of the UPS is implicated in hepatocellular carcinoma (HCC), contributing to tumor progression and therapeutic resistance. The cereblon (CRBN) E3 ubiquitin ligase complex is a crucial component of the UPS, particularly in modulating protein degradation in response to small-molecule modulators like thalidomide.

New onset refractory status epilepticus: Long-term outcomes beyond seizures.

We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps.

Prevalence of and risk factors for osteoporosis and fragility fracture in adults with cerebral palsy: A systematic review.

Aim: To systematically review the prevalence and incidence of osteoporosis, osteopenia, low bone mass, and fragility fracture in adults with cerebral palsy (CP), and identify the risk factors for osteoporosis and fracture.

Method: A systematic literature search was performed in the MEDLINE, PubMed, CINAHL, AMED, Cochrane Reviews, EMBASE, and EBM database reviews from inception until May 2024. Search terms covered a combination of keywords for CP, fracture, osteoporosis, incidence and prevalence, and risk factors.

Retrospective analysis of trauma patients transported by dispatch monitored type B ambulances to Dhulikhel Hospital, Kavre, Nepal, 2019-2023.

Background: Timely emergency medical services (EMS) are particularly important among trauma patients, as inefficient EMS systems can result in potentially avoidable death before reaching a hospital. The Dhulikhel Hospital Dispatch Center coordinates and monitors a growing network of ambulances, including seven Type B ambulances staffed with a trained prehospital care provider and medical equipment. This study evaluates the prehospital care and outcomes of trauma patients transported by Type B ambulances to Dhulikhel Hospital's Emergency Department, as monitored by the Dispatch Center.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.

Association between herpes simplex virus infection and Alzheimer's disease biomarkers: analysis within the MAPT trial.

In vitro and animal studies have suggested that inoculation with herpes simplex virus 1 (HSV-1) can lead to amyloid deposits, hyperphosphorylation of tau, and/or neuronal loss. Here, we studied the association between HSV-1 and Alzheimer's disease biomarkers in humans. Our sample included 182 participants at risk of cognitive decline from the Multidomain Alzheimer Preventive Trial who had HSV-1 plasma serology and an amyloid PET scan.

Management of Vascular Complications from Button Battery Ingestions.

Purpose: To propose a gastrointestinal bleeding management algorithm that incorporates an endoscopic and imaging scoring system and specifies management of vascular complication from button battery ingestion.

Recent Findings: Button batteries (BB) are found in many electronic devices and ingestions are associated with serious complications especially in cases of unwitnessed ingestions, prolonged impaction, and in children less than 5 years of age. Gastrointestinal bleeding from BB related vascular injury is rare but often rapidly fatal, with a mortality rate as high as 81%.

Progression of Amyloid Accumulation in Late Adulthood Among People With Childhood-Onset Epilepsy.

Background And Objectives: Previous research has demonstrated increased brain amyloid plaque load in individuals with childhood-onset epilepsy in late middle age. However, the trajectory of this process is not yet known. The aim of this study was to determine whether individuals with a history of childhood-onset epilepsy show progressive brain aging in amyloid accumulation in late adulthood (Turku Adult Childhood-Onset Epilepsy study, TACOE).

Lack of context modulation in human single neuron responses in the medial temporal lobe.

In subjects implanted with intracranial electrodes, we use two different stories involving the same person (or place) to evaluate whether and to what extent context modulates human single-neuron responses. Nearly all neurons (97% during encoding and 100% during recall) initially responding to a person/place do not modulate their response with context. Likewise, nearly none (<1%) of the initially non-responsive neurons show conjunctive coding, responding to particular persons/places in a particular context during the tasks.