Evaluating pathogenicity of variants of unknown significance in APP, PSEN1, and PSEN2.

Autosomal dominant Alzheimer's disease (ADAD) is driven by rare variants in APP, PSEN1, and PSEN2. Although more than 200 pathogenic variants in these genes are known to cause ADAD, other variants are benign, may act as risk factors, or may even reduce Alzheimer's disease risk (e.g.

Age, Sex, and Anatomical Location Patterns in Cutaneous Pyogenic Granuloma Cases.

Importance: Cutaneous pyogenic granulomas (PGs) are commonly encountered, benign, vascular tumors, in which epidemiologic factors have been variably reported, in part, due to sample size limitations and a focus on either adult or pediatric patients.

Objective: To assemble a large dataset of pathologically diagnosed PGs across the continuum of age and investigate patterns of PGs by demographic factors, including age, sex, and anatomical location.

Design, Setting, And Participants: This retrospective case series included case reports of patients with pathologically confirmed PGs of cutaneous origin reported between April 1, 2010, to March 31, 2020.

Comprehensive Analysis of TEK Variants in Patients With Vascular Malformations.

Pathogenic variants in the receptor tyrosine kinase TIE2, encoded by TEK, are known to cause vascular malformations (VMs). In this study, we retrospectively reviewed the deidentified data generated through clinical NGS testing in our laboratory and found 88 VM cases with a total of 107 clinically significant TEK variants. Among those, 23 unique variants at the amino acid level were identified, including five novel (p.

Evaluating the Role of Indocyanine Green Fluorescence Imaging in Enhancing Safety and Efficacy During Laparoscopic Cholecystectomy: A Systematic Review.

Laparoscopic cholecystectomy (LC) is the standard treatment for gallbladder disease, offering less invasive treatment and quicker recovery. However, bile duct injury (BDI) remains a critical complication. Indocyanine green (ICG) fluorescence imaging has emerged as a valuable technique to improve biliary structure visualization and potentially reduce BDI during LC.

Association of Upper GI Surgery of Great Britain and Ireland (AUGIS) Delphi consensus recommendations on the adoption of robotic upper GI surgery.

Background: The adoption of robotic platforms in upper gastrointestinal (GI) surgery is expanding rapidly. The absence of centralised guidance and governance in adoption of new surgical technologies may lead to an increased risk of patient harm.

Methods: Surgeon stakeholders participated in a Delphi consensus process following a national open-invitation in-person meeting on the adoption of robotic upper GI surgery.

The Relationship Between Isometric Midthigh Pull Force-Time Characteristics and 2-km Load-Carrying Performance in Trained British Army Soldiers.

Nevin, JP, Bowling, K, Cousens, C, Bambrough, R, and Ramsdale, M. The relationship between isometric midthigh pull force-time characteristics and 2-km load-carrying performance in trained British army soldiers. J Strength Cond Res 38(2): 360-366, 2024-Load carriage is a fundamental military occupational task.

Hyponatremia as a Marker of Complicated Appendicitis: A Retrospective Analysis.

Background The aim of this study is to investigate the potential role of hyponatremia as a biochemical predictor of complicated appendicitis. The effective employment of biochemical markers to identify early and predict progression to complicated appendicitis would be beneficial in triaging those most requiring urgent appendicectomy. A marker of interest and subject of recent study in the literature is sodium.

Delivery of a Laparoscopic Bile Duct Exploration Service as a Primary Treatment Modality for Choledocholithiasis within the NHS Healthcare System.

Introduction: The aim of this paper was to report the experience of one-stage LC and LCBDE service within a medium sized acute NHS healthcare trust to demonstrate the feasibility of this treatment modality in terms of safety, quality and effectiveness inside the limitations of the UK's nationalised healthcare system.

Methods: All patients undergoing LCBDE at our institution from November 2013 - July 2021 were included in the study. Data were collected from a prospectively maintained institutional database and data points corroborated by electronic patient data on hospital systems.

Acute appendicitis in the COVID-19 era: A complicated situation?

• Acute appendicitis is the most common intra-abdominal surgical emergency in the world. • Null hypothesis of no difference in the number of cases of complicated appendicitis. • What impact did the government's ‘Stay at Home’ message have? • Increasing body of evidence to support non-operative treatment in certain cases.

Endoloops in laparoscopic appendicectomy: A retrospective, cost effectiveness analysis.

Background: Over 50,000 appendicectomies are performed in the UK annually. Despite this highvolume. status, and the endoloop being commonly employed, there is a scarcity of literature studying differences in outcomes depending on numbers used.

Long-read genome sequencing for the molecular diagnosis of neurodevelopmental disorders.

Exome and genome sequencing have proven to be effective tools for the diagnosis of neurodevelopmental disorders (NDDs), but large fractions of NDDs cannot be attributed to currently detectable genetic variation. This is likely, at least in part, a result of the fact that many genetic variants are difficult or impossible to detect through typical short-read sequencing approaches. Here, we describe a genomic analysis using Pacific Biosciences circular consensus sequencing (CCS) reads, which are both long (>10 kb) and accurate (>99% bp accuracy).

The Therapeutic Odyssey: Positioning Genomic Sequencing in the Search for a Child's Best Possible Life.

The desire of parents to obtain a genetic diagnosis for their child with intellectual disability and associated symptoms has long been framed as a diagnostic odyssey, an arduous and sometimes perilous journey focused on the goal of identifying a cause for the child's condition. Semi-structured interviews (N = 60) were conducted with parents of children (N = 59, aged 2-24 years) with intellectual disability and/or developmental delay (IDD) who underwent genome sequencing at a single pediatric multispecialty clinic. Interviews were conducted after parents received their child's sequencing result (positive findings, negative findings, or variants of unknown significance).

Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage-sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, we describe the clinical features in 25 novel individuals with 20 distinct, clinically relevant variants in BPTF, including four individuals with inherited changes in BPTF.

A state-based approach to genomics for rare disease and population screening.

Purpose: The Alabama Genomic Health Initiative (AGHI) is a state-funded effort to provide genomic testing. AGHI engages two distinct cohorts across the state of Alabama. One cohort includes children and adults with undiagnosed rare disease; a second includes an unselected adult population.

Variant Classification Concordance using the ACMG-AMP Variant Interpretation Guidelines across Nine Genomic Implementation Research Studies.

Harmonization of variant pathogenicity classification across laboratories is important for advancing clinical genomics. The two CLIA-accredited Electronic Medical Record and Genomics Network sequencing centers and the six CLIA-accredited laboratories and one research laboratory performing genome or exome sequencing in the Clinical Sequencing Evidence-Generating Research Consortium collaborated to explore current sources of discordance in classification. Eight laboratories each submitted 20 classified variants in the ACMG secondary finding v.

Identifying rare, medically relevant variation via population-based genomic screening in Alabama: opportunities and pitfalls.

Purpose: To evaluate the effectiveness and specificity of population-based genomic screening in Alabama.

Methods: The Alabama Genomic Health Initiative (AGHI) has enrolled and evaluated 5369 participants for the presence of pathogenic/likely pathogenic (P/LP) variants using the Illumina Global Screening Array (GSA), with validation of all P/LP variants via Sanger sequencing in a CLIA-certified laboratory before return of results.

Results: Among 131 variants identified by the GSA that were evaluated by Sanger sequencing, 67 (51%) were false positives (FP).

Cost effectiveness of intraoperative laparoscopic ultrasound for suspected choledocholithiasis; outcomes from a specialist benign upper gastrointestinal unit.

Introduction: Common bile duct stones are present in 10% of patients with symptomatic gallstones. One-third of UK patients undergoing cholecystectomy will have preoperative ductal imaging, commonly with magnetic resonance cholangiopancreatography. Intraoperative laparoscopic ultrasound is a valid alternative but is not widely used.

A rare late complication of traumatic diaphragmatic hernia repair.

We report a case of sudden cardiovascular collapse several weeks following surgical repair of a traumatic diaphragmatic hernia. The patient presented with features of circulatory shock without a clear diagnosis, therefore an urgent computed tomography scan of the chest and abdomen was undertaken, which revealed a pericardial effusion with evidence of cardiac tamponade. Ultrasound-guided needle pericardiocentesis with aspiration of blood from the pericardial sac in the Emergency Department provided an immediate response and her cardiac output improved.