Repeat expansions in gene in refractory chronic cough.

Introduction: Refractory chronic cough (RCC), persisting despite addressing contributory diagnoses, is likely underpinned by neurally mediated cough hypersensitivity. disorders are genetic neurodegenerative conditions caused by biallelic repeat expansion sequences, commonly presenting with cough, followed by neurological features including cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). The prevalence and identifying clinical characteristics of repeat-expansion disorders in patients with RCC are unknown.

Cost-effectiveness of follow-up algorithms for chronic thromboembolic pulmonary hypertension in pulmonary embolism survivors.

Introduction: Achieving an early diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) in pulmonary embolism (PE) survivors results in better quality of life and survival. Importantly, dedicated follow-up strategies to achieve an earlier CTEPH diagnosis involve costs that were not explicitly incorporated in the models assessing their cost-effectiveness. We performed an economic evaluation of 11 distinct PE follow-up algorithms to determine which should be preferred.

Reversal of inflammatory reprogramming by vasodilator agents in pulmonary hypertension.

Background: Pulmonary arterial hypertension (PAH) is a deadly disease without effective non-invasive diagnostic and prognostic testing. It remains unclear whether vasodilators reverse inflammatory activation, a part of PAH pathogenesis. Single-cell profiling of inflammatory cells in blood could clarify these PAH mechanisms.

variant may affect the response to type 2 biologics in patients with severe asthma.

Background: Asthma is a heterogeneous disease with variable response to treatment. Genetic backgrounds are involved in the severity of type 2 asthma, but their effects on responses to biologics remain unknown. This study aimed to clarify the role of genetic factors in response to biologics in patients with severe asthma.

Barriers to and enablers of physical activity and its association with daily steps after hospitalisation for a COPD exacerbation: what patients say matters.

Introduction: Exacerbations of COPD decrease physical activity. Physical activity interventions after these events are desirable but have had mixed results. Understanding the barriers to and enablers of physical activity may help to improve the results of these interventions.

Therapeutic doses of efzofitimod demonstrate efficacy in pulmonary sarcoidosis.

Background: In a phase 1b/2a clinical trial of efzofitimod in patients with corticosteroid-requiring pulmonary sarcoidosis, treatment resulted in dose-dependent improvement in key end-points. We undertook a analysis pooling dose arms that achieved therapeutic concentrations of efzofitimod (Therapeutic group) those that did not (Subtherapeutic group).

Methods: Peripheral blood mononuclear cells incubated with tuberculin-coated beads were exposed to varying concentrations of efzofitimod in an assay to determine concentrations that inhibited granuloma formation.

The impact of highly effective modulator therapy on sinusitis and dysosmia in young children with cystic fibrosis: a prospective study protocol.

Background: Chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) are prevalent disease complications in people with cystic fibrosis. These understudied comorbidities significantly impact quality of life. The impact of highly effective modulator therapy (HEMT) in young children with cystic fibrosis (YCwCF) on these disease complications is unknown.

Clinical improvements after endoscopic lung volume reduction with valves in patients with advanced emphysema and a 6-min walk test ≤140 m at baseline.

Background: Data regarding the effectiveness and safety of endoscopic lung volume reduction with valves (ELVR) in emphysema patients with a very low 6-min walk test (6MWT) are limited. Patients with severe emphysema and very low exercise capacity, as indicated by a 6MWT ≤140 m, are often excluded from clinical studies on ELVR, assuming limited therapeutic benefits and increased complication risk.

Study Designs And Methods: This study utilised data from the Lungenemphysemregister e.

Variability in disease severity among cystic fibrosis patients carrying residual-function variants: data from the European Cystic Fibrosis Society Patient Registry.

Background: People with cystic fibrosis (CF) variants that exhibit residual function (RF) of the CF transmembrane conductance regulator are considered to have a milder disease; however, the spectrum of CF phenotype within the different RF variants has not been extensively investigated. The aim of the present study was to characterise the spectrum of CF disease severity in people with CF (pwCF) carrying different RF variants, using the European Cystic Fibrosis Society Patient Registry (ECFSPR) data.

Methods: A retrospective cross-sectional and longitudinal cohort study included data from the ECFSPR during 2008-2016.

Inhaled alpha-1 antitrypsin (AAT) restores lower respiratory tract protease-antiprotease homoeostasis and reduces inflammation in AAT-deficient individuals: a randomised phase 2 study.

Background: Alpha-1 antitrypsin (AAT)-deficient individuals have a greater risk for developing COPD than individuals with normal AAT levels.

Methods: This was a double-blind, randomised, parallel group, placebo-controlled trial to examine the safety and tolerability of "Kamada-AAT for Inhalation" (inhaled AAT) in subjects with AAT deficiency, and to explore its effect on AAT and biomarkers in the lung epithelial lining fluid (ELF). 36 patients with severe AAT deficiency were randomised 2:1 to receive 80 mg or 160 mg inhaled AAT or placebo once daily for 12 weeks.

Association between impaired diffusion capacity and small airway dysfunction: a cross-sectional study.

Background: Small airway dysfunction (SAD) and impaired diffusion capacity of the lungs for carbon monoxide ( ) are positively associated with a worse prognosis. Individuals with both dysfunctions have been identified in clinical practice and it is unknown whether they have worse health status or need management. We conducted this study to explore the association between SAD and impaired , and the difference between the groups with two dysfunctions, with either one dysfunction and with no dysfunction.

Neoadjuvant chemoradiotherapy up-regulates PD-L1 in radioresistant colorectal cancer.

Background: Combining radiotherapy (RT) with immune checkpoint inhibitors (ICIs) is a promising strategy that can enhance the therapeutic efficacy of ICIs. However, little is known about RT-induced changes in the expression of immune checkpoints, such as PD-L1, and their clinical implications in colorectal cancer (CRC). This study aimed to investigate the association between responsiveness to RT and changes in PD-L1 expression in human CRC tissue and cell lines.

Unveiling immunity gaps and determining a suitable age for a third dose of the measles-containing vaccine: a strategic approach to accelerating measles elimination.

Background: In highly measles immunized countries, immunity gaps in adolescents and young adults are a key issue posing an obstacle to measles elimination. This study aims to identify the gaps by estimating the age-stratified probability of seropositivity, and to ascertain a suitable age for the administration of a third dose of a measles-containing vaccine (MCV3) to effectively fill these gaps.

Methods: We retrospectively obtained measles serological results from hospital setting among among individuals aged 13-39 years and developed a serocatalytic dynamic probability model, stratifying seropositivity due to vaccination or natural infection.

Customizable large-scale HPLC fraction collection using low-cost 3D printing.

High-performance liquid chromatography (HPLC) is an invaluable technique that has been used for many decades for the separation of various molecules. The reproducible collection of eluates from these systems has been significantly improved via its automation by fraction collection systems. Current commercially available fraction collectors are not easily customizable, incompatible with other platforms, and come with a large cost barrier making them inaccessible to many researchers.

Interplay between creeping fat and gut microbiota: A brand-new perspective on fecal microbiota transplantation in Crohn's disease.

Inflammatory bowel disease, particularly Crohn's disease (CD), has been linked to modifications in mesenteric adipose tissue (MAT) and the phenomenon known as "creeping fat" (CrF). The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD. Notably, the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence, indicating the significant role of MAT in the pathogenesis of CD.

Prognostic model for esophagogastric variceal rebleeding after endoscopic treatment in liver cirrhosis: A Chinese multicenter study.

Background: Rebleeding after recovery from esophagogastric variceal bleeding (EGVB) is a severe complication that is associated with high rates of both incidence and mortality. Despite its clinical importance, recognized prognostic models that can effectively predict esophagogastric variceal rebleeding in patients with liver cirrhosis are lacking.

Aim: To construct and externally validate a reliable prognostic model for predicting the occurrence of esophagogastric variceal rebleeding.

Human leukocyte antigen and donor-specific antibodies in liver transplantation.

In this article, we comment on an article published in a recent issue of the . We specifically focus on the roles of human leukocyte antigen (HLA) and donor-specific antibodies (DSAs) in pediatric liver transplantation (LT), as well as the relationship between immune rejection after LT and DSA. Currently, LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.

Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEWS pharmacokinetics study.

Background: Ulcerative colitis (UC) is a chronic inflammatory condition requiring continuous treatment and monitoring. There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.

Aim: To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.

Advances and challenges in diagnosing and managing adult autoimmune enteropathy.

Autoimmune enteropathy (AIE) is a rare immune mediated disorder primarily affecting children, characterized by chronic diarrhea, malabsorption, vomiting, weight loss and villous atrophy. It has also been observed in adults presenting diagnostic and treatment challenges due to its overlap with other gastrointestinal disorders such as celiac disease. Initial diagnostic criteria for AIE include small bowel villous atrophy, lack of response to dietary restrictions, presence of anti-enterocyte antibodies, and predisposition to autoimmunity without severe immunodeficiency.

Imaging characteristics of hypervascular focal nodular hyperplasia-like lesions in patients with chronic alcoholic liver disease.

Background: Focal nodular hyperplasia (FNH)-like lesions are hyperplastic formations in patients with micronodular cirrhosis and a history of alcohol abuse. Although pathologically similar to hepatocellular carcinoma (HCC) lesions, they are benign. As such, it is important to develop methods to distinguish between FNH-like lesions and HCC.

Exploring gut microbiota as a novel therapeutic target in Crohn's disease: Insights and emerging strategies.

Extensive research has investigated the etiology of Crohn's disease (CD), encompassing genetic predisposition, lifestyle factors, and environmental triggers. Recently, the gut microbiome, recognized as the human body's second-largest gene pool, has garnered significant attention for its crucial role in the pathogenesis of CD. This paper investigates the mechanisms underlying CD, focusing on the role of 'creeping fat' in disease progression and exploring emerging therapeutic strategies, including fecal microbiota transplantation, enteral nutrition, and therapeutic diets.

Environmental impact of commonly used anaesthetic agents: systematic literature review with narrative synthesis.

Background: Increasing awareness of the potential environmental impact of volatile anaesthetic agents has stimulated increased use of total i.v. anaesthesia.

Restoring hematopoietic stem and progenitor cell function in mice by delivery of RNA lipid nanoparticles.

Fanconi anemia (FA) is a congenital multisystem disorder characterized by early-onset bone marrow failure (BMF) and cancer susceptibility. While gene addition and repair therapies are being considered as treatment options, depleted hematopoietic stem cell (HSC) pools, poor HSC mobilization, compromised survival during transduction, and increased sensitivity to conventional conditioning strategies limit eligibility for FA patients to receive gene therapies. As an alternative approach, we explored protein replacement by mRNA delivery via lipid nanoparticles (LNPs).

Denial as an ethical problem: the example of ICU triage in the context of the COVID-19 pandemic.

Objectives: The overall goal of this article is to show that denial is one of the greatest obstacles to good practical judgment and is therefore a major problem in clinical ethics by examining its cognitive structure and the challenges it poses for clinical ethics consultation and intervention. In addition to clinical examples, excerpts of verbatim from citizen forums on triage protocols will be used to illustrate the manifestations of denial in citizens when faced with difficult choices.

Case Presentation: The initial waves of the pandemic and the alarming resurgence of cases with the emergence of highly transmissible variants have created increased pressure on many healthcare systems around the world.

3D-printed constructs deliver bioactive cargos to expedite cartilage regeneration.

Cartilage is solid connective tissue that recovers slowly from injury, and pain and dysfunction from cartilage damage affect many people. The treatment of cartilage injury is clinically challenging and there is no optimal solution, which is a hot research topic at present. With the rapid development of 3D printing technology in recent years, 3D bioprinting can better mimic the complex microstructure of cartilage tissue and thus enabling the anatomy and functional regeneration of damaged cartilage.