An ANXA11 P93S variant dysregulates TDP-43 and causes corticobasal syndrome.

Introduction: Variants of uncertain significance (VUS) surged with affordable genetic testing, posing challenges for determining pathogenicity. We examine the pathogenicity of a novel VUS P93S in Annexin A11 (ANXA11) - an amyotrophic lateral sclerosis/frontotemporal dementia-associated gene - in a corticobasal syndrome kindred. Established ANXA11 mutations cause ANXA11 aggregation, altered lysosomal-RNA granule co-trafficking, and transactive response DNA binding protein of 43 kDa (TDP-43) mis-localization.

Snuffbox distal transradial access (dTRA) for arteriovenous fistuloplasty in Singapore: Going distal is safe.

Aim: Arteriovenous fistula (AVF) dysfunction resulting from stenosis or occlusion, is a prevalent issue in end-stage renal failure patients reliant on autogenous AVFs for dialysis. Recently, a distal transradial approach (dTRA) has emerged, offering advantages such as diminished access site complications, better patient comfort and reduced risk of radial artery occlusion. Our study seeks to assess the effectiveness, outcomes and complication rates of employing dTRA for arteriovenous fistuloplasty in Singaporean patients.

Mis-spliced transcripts generate de novo proteins in TDP-43-related ALS/FTD.

Functional loss of TDP-43, an RNA binding protein genetically and pathologically linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leads to the inclusion of cryptic exons in hundreds of transcripts during disease. Cryptic exons can promote the degradation of affected transcripts, deleteriously altering cellular function through loss-of-function mechanisms. Here, we show that mRNA transcripts harboring cryptic exons generated de novo proteins in TDP-43-depleted human iPSC-derived neurons in vitro, and de novo peptides were found in cerebrospinal fluid (CSF) samples from patients with ALS or FTD.

Advances in molecular pathology, diagnosis, and treatment of amyotrophic lateral sclerosis.

Although the past two decades have produced exciting discoveries in the genetics and pathology of amyotrophic lateral sclerosis (ALS), progress in developing an effective therapy remains slow. This review summarizes the critical discoveries and outlines the advances in disease characterization, diagnosis, imaging, and biomarkers, along with the current status of approaches to ALS care and treatment. Additional knowledge of the factors driving disease progression and heterogeneity will hopefully soon transform the care for patients with ALS into an individualized, multi-prong approach able to prevent disease progression sufficiently to allow for a dignified life with limited disability.

An P93S variant dysregulates TDP-43 and causes corticobasal syndrome.

As genetic testing has become more accessible and affordable, variants of uncertain significance (VUS) are increasingly identified, and determining whether these variants play causal roles in disease is a major challenge. The known disease-associated Annexin A11 (ANXA11) mutations result in ANXA11 aggregation, alterations in lysosomal-RNA granule co-trafficking, and TDP-43 mis-localization and present as amyotrophic lateral sclerosis or frontotemporal dementia. We identified a novel VUS in ANXA11 (P93S) in a kindred with corticobasal syndrome and unique radiographic features that segregated with disease.

Scrotal Wall Metastasis from Adenocarcinoma of Unknown Origin, with Concurrent Extramammary Paget's Disease - a Case Report.

Introduction: Scrotal cancer is a very rare disease, with the most common subtype being squamous cell carcinoma. Metastatic carcinoma to the scrotal wall is very rare. A histological finding of adenocarcinoma in a scrotal malignancy invariably suggests a metastasis from another primary cancer.

The Utility of Ultrasound Guidance to Improve the Safety of Closure of Antegrade Common Femoral Artery Access after Lower Limb Revascularization.

This study aimed to investigate the feasibility of ultrasound (US)-guidance in reducing adverse event (AE) rates when using Angioseal device during antegrade lower limb angioplasty via common femoral artery access. From December 2016 to November 2022, 1,322 patients were identified, including 1,131 (85.6%) patients who underwent US-guided closure and 191 (14.

Cognitive determinants of decisional capacity in neurodegenerative disorders.

Objective: Cognitive contributions to decisional capacity are complex and not well understood. Capacity to consent for research has been linked to executive function, but executive function assessment tools are imperfect. In this study, we examine the relationship between decisional capacity and a newly developed executive function composite score and determine whether cognitive performance can predict impaired decisional capacity.

Mis-spliced transcripts generate proteins in TDP-43-related ALS/FTD.

Functional loss of TDP-43, an RNA-binding protein genetically and pathologically linked to ALS and FTD, leads to inclusion of cryptic exons in hundreds of transcripts during disease. Cryptic exons can promote degradation of affected transcripts, deleteriously altering cellular function through loss-of-function mechanisms. However, the possibility of protein synthesis from cryptic exon transcripts has not been explored.

Amyotrophic lateral sclerosis mimics.

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disorder characterized by progressive degeneration of cortical, bulbar, and spinal motor neurons. When a patient presents with a progressive upper and/or lower motor syndrome, clinicians must pay particular attention to any atypical features in the history and/or clinical examination suggesting an alternate diagnosis, as up to 10% percent of patients initially diagnosed with ALS have a mimic of ALS. ALS is a clinical diagnosis and requires the exclusion of other disorders that may have similar presentations but a more favorable prognosis or an effective therapy.

The Efficacy of Clinical Tests to Diagnose Evaporative Dry Eye Disease Related to Meibomian Gland Dysfunction.

Objectives: To determine the efficacy of widely available subtype clinical tests to characterize evaporative dry eye disease (EDED) related to meibomian gland dysfunction (MGD) compared to normal and to validate those clinical cut points in an independent sample.

Methods: A diagnostic accuracy study (52 subjects), an investigator-masked study, was followed by a larger independent sample (364 subjects) analysis to confirm efficacy in normal and EDED subjects. All subjects were 18 years of age and older and were classified using a battery of clinical tests for dry eye that included symptoms, tear meniscus height, tear stability, ocular staining, evaporative-specific tests, and the Schirmer I test.

Validation of the Modified Schein Dry Eye Symptom Questionnaire and Comparison With the Ocular Surface Disease Index.

Purpose: This study evaluated the validity and diagnostic efficacy of a modified Schein dry eye questionnaire and compared it to the Ocular Surface Disease Index (OSDI).

Methods: The original Schein survey was modified to allow numerical scoring on a 0 to 24 scale and evaluated in prospective studies in normal and dry eye subjects. Receiver operating characteristic (ROC) analysis for test efficacy in aqueous deficient dry eye (ADDE) and evaporative dry eye (EDE) related to meibomian gland dysfunction was determined.

Morphological characteristics of Meibomian Glands and their Influence on Dry Eye disease in contact lens wearers.

Purpose: Meibomian glands (MG) are now easily imaged via clinical meibography machines. The purpose of this work was to explore the utility of the known MG morphology metrics for predicting dry eye disease (DED) in contact lens (CL) wearers.

Methods: Successful and previous CL wearers were recruited.

Single-centre experience with endovascular rotational thrombectomy for single session salvage of thrombosed arteriovenous fistulas and grafts.

Objectives: This paper documents our experience and outcomes of using a relatively new endovascular rotational thrombectomy device for salvage of thrombosed vascular access.

Methodology: A retrospective study reviewing patients with thrombosed native AVF or AVG who underwent endovascular declotting using a rotational thrombectomy device between November 2018 and May 2020 at a tertiary university hospital in Southeast Asia. We evaluated demographics, procedural data, technical and procedural success, patency rates and complications.

Computerized tomography scan in acute appendicitis with eventual negative appendectomy.

Background And Aim: Acute appendicitis (AA) is traditionally considered a clinical diagnosis and negative appendectomy (NA) rates vary across health-care systems. Computed tomography (CT) scans have been shown to aid in the reduction of NA rates. Our study aimed to determine the pre-operative imaging characteristics in patients undergoing appendectomy with eventual normal histology.

Randomized Controlled Trial Comparing Drug-coated Balloon Angioplasty versus Conventional Balloon Angioplasty for Treating Below-the-Knee Arteries in Critical Limb Ischemia: The SINGA-PACLI Trial.

Background There is a paucity of randomized trials demonstrating superior efficacy of drug-coated balloon angioplasty (DCBA) compared with conventional percutaneous transluminal angioplasty (PTA) for below-the-knee arterial disease in patients with -critical limb ischemia. Purpose To compare DCBA versus PTA for below-the-knee lesions in participants with critical limb ischemia through 12 months. Materials and Methods In this prospective, randomized, two-center, double-blind superiority study, participants with critical limb ischemia with rest pain or tissue loss with atherosclerotic disease in the native below-the-knee arteries were randomly assigned (in a one-to-one ratio) to DCBA or PTA after stratification for diabetes and renal failure between November 2013 and October 2017.

Improving the efficacy of exome sequencing at a quaternary care referral centre: novel mutations, clinical presentations and diagnostic challenges in rare neurogenetic diseases.

Background: We used a multimodal approach including detailed phenotyping, whole exome sequencing (WES) and candidate gene filters to diagnose rare neurological diseases in individuals referred by tertiary neurology centres.

Methods: WES was performed on 66 individuals with neurogenetic diseases using candidate gene filters and stringent algorithms for assessing sequence variants. Pathogenic or likely pathogenic missense variants were interpreted using in silico prediction tools, family segregation analysis, previous publications of disease association and relevant biological assays.

Combined Biopsy and Imaging-Guided Microwave Ablation by Using a Coaxial Guiding Needle.

This article demonstrates the technique of using a coaxial guiding needle to perform combined percutaneous biopsy and microwave ablation via a single tract. From May 2019 to July 2020, 14 patients underwent combined biopsy and microwave ablation by using a coaxial guiding cannula. Tumors were in the kidney of six patients (43%), the liver of six patients (43%), and the lung in two patients (14%).

Guillain-Barré Syndrome and Other Acute Polyneuropathies.

Guillain-Barré syndrome (GBS) is an acute autoimmune neuropathy that can cause motor, sensory, and autonomic symptoms. Although GBS primarily is a neuropathic disorder, multiple organ systems can be affected during the disease course, and older patients may be more vulnerable to systemic complications. Close clinical monitoring and early interventions using pharmacologic and nonpharmacological treatments may lead to an improved long-term outcome.

Advanced Techniques in the Percutaneous Ablation of Liver Tumours.

Percutaneous ablation is an accepted treatment modality for primary hepatocellular carcinoma (HCC) and liver metastases. The goal of curative ablation is to cause the necrosis of all tumour cells with an adequate margin, akin to surgical resection, while minimising local damage to non-target tissue. Aside from the ablative modality, the proceduralist must decide the most appropriate imaging modality for visualising the tumour and monitoring the ablation zone.

Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis.

The liver is frequently the most common site of metastasis in patients with colorectal cancer, occurring in more than 50% of patients. While surgical resection remains the only potential curative option, it is only eligible in 15-20% of patients at presentation. In the past two decades, major advances in modern chemotherapy and personalized biological agents have improved overall survival in patients with unresectable liver metastasis.