In vivo CRISPR-Cas9 genome editing in mice identifies genetic modifiers of somatic CAG repeat instability in Huntington's disease.

Huntington's disease, one of more than 50 inherited repeat expansion disorders, is a dominantly inherited neurodegenerative disease caused by a CAG expansion in HTT. Inherited CAG repeat length is the primary determinant of age of onset, with human genetic studies underscoring that the disease is driven by the CAG length-dependent propensity of the repeat to further expand in the brain. Routes to slowing somatic CAG expansion, therefore, hold promise for disease-modifying therapies.

A Practical Clinical Approach to Navigate Pulmonary Embolism Management: A Primer and Narrative Review of the Evolving Landscape.

Advances in imaging, pharmacological, and procedural technologies have rapidly expanded the care of pulmonary embolism. Earlier, more accurate identification and quantification has enhanced risk stratification across the spectrum of the disease process, with a number of clinical tools available to prognosticate outcomes and guide treatment. Direct oral anticoagulants have enabled a consistent and more convenient long-term therapeutic option, with a greater shift toward outpatient treatment for a select group of low-risk patients.

Suppression of Huntington's Disease Somatic Instability by Transcriptional Repression and Direct CAG Repeat Binding.

Huntington's disease (HD) arises from a CAG expansion in the () gene beyond a critical threshold. A major thrust of current HD therapeutic development is lowering levels of mutant mRNA (m) and protein (mHTT) with the aim of reducing the toxicity of these product(s). Human genetic data also support a key role for somatic instability (SI) in 's CAG repeat - whereby it lengthens with age in specific somatic cell types - as a key driver of age of motor dysfunction onset.

Twenty-five years of observations from the International Registry of Acute Aortic Dissection (IRAD) and its impact on the cardiovascular scientific community.

Objective: The International Registry of Acute Aortic Dissection (IRAD) celebrated its 25th anniversary in January 2021. This study evaluated IRAD's role in promoting the understanding and management of acute aortic dissection (AD) over these years.

Methods: IRAD studies were identified, analyzed, and ranked according to their citations per year (c/y) to determine the most-cited IRAD studies and topics.

Meals, Microbiota and Mental Health in Children and Adolescents (MMM-Study): A protocol for an observational longitudinal case-control study.

Recent studies indicate that the interplay between diet, intestinal microbiota composition, and intestinal permeability can impact mental health. More than 10% of children and adolescents in Iceland suffer from mental disorders, and rates of psychotropics use are very high. The aim of this novel observational longitudinal case-control study, "Meals, Microbiota and Mental Health in Children and Adolescents (MMM-Study)" is to contribute to the promotion of treatment options for children and adolescents diagnosed with mental disorders through identification of patterns that may affect the symptoms.

Expertise in colonoscopy intubation does not predict diagnostic accuracy: a simulation-based study.

 Studies have linked cecal intubation rate with adenoma detection rate; however, the direct association between technical performance during colonoscopy intubation and withdrawal has never been explored. Thus, it remains unclear whether gentle and efficient intubation predicts superior mucosal inspection. The aim of this study was to investigate the correlation between performance during intubation and withdrawal in a simulation-based setup.

Colonoscope retraction technique and predicting adenoma detection rate: a multicenter study.

Background And Aims: The success of preventing colorectal cancer relies on the expertise of the colonoscopists. Studies suggest that the retraction technique is a powerful indicator of expertise in distinguishing endoscopists with various adenoma detection rates (ADRs). We aimed to develop a retraction technique score and explore the correlation between endoscopists' retraction technique and their ADRs.

Plasma concentrations of perfluoroalkyl substances and risk of inflammatory bowel diseases in women: A nested case control analysis in the Nurses' Health Study cohorts.

Background: Perfluoroalkyl substances (PFASs) are synthetic compounds used in a wide variety of industrial and consumer applications. An association between PFAS exposure and risk of ulcerative colitis (UC) has been reported in a highly exposed population. However, data are limited on risk of inflammatory bowel diseases (IBD) among individuals with background population levels of PFAS exposure.

Machine-learning-based predictions of direct-acting antiviral therapy duration for patients with hepatitis C.

Introduction: Hepatitis C, which affects 71 million persons worldwide, is the most common blood-borne pathogen in the United States. Chronic infections can be treated effectively thanks to the availability of modern direct-acting antiviral (DAA) therapies. Real-world data on the duration of DAA therapy, which can be used to optimize and guide the course of therapy, may also be useful in determining quality of life enhancements based upon total required supply of medication and long-term improvements to quality of life.

Bariatric surgery in the treatment of adolescent obesity: current perspectives in the United States.

: Rates of severe obesity in adolescents have increased at an alarming rate. Unfortunately, there are limited successful treatments for severe obesity in adolescents. Metabolic and bariatric surgery (MBS) is the most effective treatment available for adolescents with Class 2 and above severe obesity and has demonstrated variable degrees of sustained long-term weight loss which leads to resolution of multiple associated conditions and an improved quality of life.

SARS-CoV-2 can infect the placenta and is not associated with specific placental histopathology: a series of 19 placentas from COVID-19-positive mothers.

Congenital infection of SARS-CoV-2 appears to be exceptionally rare despite many cases of COVID-19 during pregnancy. Robust proof of placental infection requires demonstration of viral localization within placental tissue. Only two of the few cases of possible vertical transmission have demonstrated placental infection.

A comprehensive evaluation of apixaban in the treatment of venous thromboembolism.

: The emergence of the direct oral anticoagulants (DOACs) offers patients more convenient and accessible alternatives to warfarin or parenteral agents for the treatment of venous thromboembolism (VTE). Apixaban (Eliquis®) is an oral, direct factor Xa inhibitor that is approved for the acute treatment of deep-vein thrombosis (DVT) and pulmonary embolism (PE) as well as for the reduction in the risk of recurrent DVT and PE following initial therapy.: This article reviews results from preclinical and healthy volunteer studies, large phase III trials evaluating the safety and efficacy of apixaban, as well as key studies that led to apixaban's current licensing.

Pulmonary embolism response teams: Purpose, evidence for efficacy, and future research directions.

Pulmonary embolism (PE) is a major cause of morbidity and mortality in the United States. Although new therapeutic tools and strategies have recently been developed for the diagnosis and treatment of patients with PE, the outcomes for patients who present with massive or high-risk PE remain dismal. To address this crisis, pulmonary embolism response teams (PERTs) are being created around the world in an effort to immediately and simultaneously engage multiple specialists to determine the best course of action and coordinate the clinical care for patients with acute PE.

Total Elbow Arthroplasty.

Total elbow arthroplasty design has evolved in recent decades. Indications for total elbow arthroplasty include advanced rheumatoid arthritis to osteoarthritis, post-traumatic arthritis, adverse sequelae of trauma, and unreconstructable acute fractures. This article summarizes the current evidence for total elbow arthroplasty, including the history of total elbow arthroplasty, an overview of the recent trends and designs, and current evidence-based outcomes.

When pain gets stuck: the evolution of pain chronification and treatment resistance.

It is well-recognized that, despite similar pain characteristics, some people with chronic pain recover, whereas others do not. In this review, we discuss possible contributions and interactions of biological, social, and psychological perturbations that underlie the evolution of treatment-resistant chronic pain. Behavior and brain are intimately implicated in the production and maintenance of perception.

Pulmonary Embolism Response Team: Inpatient Structure, Outpatient Follow-up, and Is It the Current Standard of Care?

Pulmonary Embolism Response Teams (PERTs) are being created around the United States to immediately and simultaneously bring together multiple specialists to determine the best course of action and coordinate clinical care for patients with severe pulmonary embolism (PE). The organization and structure of each PERT will depend on local clinical demands and resources. Creating a follow up clinic for PE patients after discharge from the hospital is an essential component of any PERT program.

HER kinase inhibition in patients with HER2- and HER3-mutant cancers.

Somatic mutations of ERBB2 and ERBB3 (which encode HER2 and HER3, respectively) are found in a wide range of cancers. Preclinical modelling suggests that a subset of these mutations lead to constitutive HER2 activation, but most remain biologically uncharacterized. Here we define the biological and therapeutic importance of known oncogenic HER2 and HER3 mutations and variants of unknown biological importance by conducting a multi-histology, genomically selected, 'basket' trial using the pan-HER kinase inhibitor neratinib (SUMMIT; clinicaltrials.

Presentation, Diagnosis, and Outcomes of Acute Aortic Dissection: 17-Year Trends From the International Registry of Acute Aortic Dissection.

Background: Diagnosis, treatment, and outcomes of acute aortic dissection (AAS) are changing.

Objectives: This study examined 17-year trends in the presentation, diagnosis, and hospital outcomes of AAD from the International Registry of Acute Aortic Dissection (IRAD).

Methods: Data from 4,428 patients enrolled at 28 IRAD centers between December 26, 1995, and February 6, 2013, were analyzed.

Predicting in-hospital mortality in acute type B aortic dissection: evidence from International Registry of Acute Aortic Dissection.

Background: The outcome of patients with acute type B aortic dissection (ABAD) is strongly related to their clinical presentation. The purpose of this study was to investigate predictors for mortality among patients presenting with ABAD and to create a predictive model to estimate individual risk of in-hospital mortality using the International Registry of Acute Aortic Dissection (IRAD).

Methods And Results: All patients with ABAD enrolled in IRAD between 1996 and 2013 were included for analysis.

Analytical and clinical comparison of two fully automated immunoassay systems for the diagnosis of celiac disease.

Objective: Here we compared analytical and clinical performance characteristics of two novel automated assay systems for the detection of celiac disease (CD) specific antibodies: QUANTA Flash (INOVA Diagnostics, Inc.) and EliA (Thermo Scientific).

Methods: A total of 74 biopsy-proven CD patients (2 with IgA deficiency) and 138 controls were tested by both methods.

Painless Type B Aortic Dissection: Insights From the International Registry of Acute Aortic Dissection.

Introduction: The classical presentation of a patient with Type B acute aortic dissection (TBAAD) is characterized by severe chest, back, or abdominal pain, ripping or tearing in nature. However, some patients present with painless acute aortic dissection, which can lead to a delay in diagnosis and treatment. We utilized the International Registry on Acute Aortic Dissections (IRAD) database to study these patients.

Balancing accountability and improvement: a case study from Massachusetts.

Background: The Massachusetts Health Quality Partnership (MHQP), a coalition of health care providers and insurers, and business and government organizations, conducted a voluntary statewide survey about patients' experiences with inpatient care at Massachusetts hospitals in 1998, and made the results public.

Methods: MHQP contracted with The Picker Institute (Boston) to conduct the statewide survey about seven dimensions of care for adult medical, surgical, and maternity patients at 58 hospitals across Massachusetts. The communications strategy for public report release was designed to promote fair reporting by the news media and emphasize the improvement goals of performance measurement above evaluation.

Piloting nursing-sensitive hospital care measures in Massachusetts.

Under the umbrella of the Massachusetts Hospital Association and Massachusetts Organization of Nurse Executives Patients First Initiative, Massachusetts hospitals tested a subset of NQF-endorsed nursing-sensitive care measures in 2006. In this report, we describe the pilot test, report on pilot test measure data, summarize participant feedback on the tested measures, and offer observations on lessons learned from the pilot test.