Right ventricular strain impairment due to hypoxia in patients with COPD: a post hoc analysis of two randomised controlled trials.

Background: Hypoxic pulmonary vasoconstriction leads to an increase in pulmonary artery pressure (PAP) and potentially right heart failure in healthy individuals and patients with respiratory diseases. Previous studies in patients with chronic obstructive pulmonary disease (COPD) exposed to hypobaric hypoxia have shown an increase in PAP, while traditional echocardiographic parameters revealed only minimal changes at high altitude. Speckle-tracking-derived analysis is potentially more sensitive to assess right ventricular (RV) function and we used this method to investigate the impact on RV function of patients with COPD ascending to high altitude and compared the results with the traditional echocardiographic parameters.

Design and cohort characteristics of TRACK, a prospective study of hyperkalaemia management decision-making.

Background: Guideline-recommended hyperkalaemia management includes dietary potassium (K) restriction, bicarbonate correction, diuretics and K binders with dose reduction of renin-angiotensin-aldosterone system inhibitors as a last resort. The extent to which these recommendations are implemented is uncertain, as real-world data on hyperkalaemia management are limited. The Tracking Treatment Pathways in Adult Patients with Hyperkalemia (TRACK) study is a multinational, prospective, longitudinal study that is being conducted to address this knowledge gap.

Outcomes using inverted iliac limb bifurcate components in fenestrated/branched endografting.

Background: The use of standard bifurcate pieces in fenestrated/branched endovascular aortic repair (F/BEVAR) requires adequate length from the lowest branch or fenestration to the aortic bifurcation. In patients with prior aortic surgery, the aortic bifurcation is often artificially established in a more proximal position, compromising the infrarenal length, which hinders the placement of a standard bifurcate component below the fenestrated/branched component. Short bifurcate bodies using an inverted contralateral limb have been purpose-built to address this challenge.

Progressive Kidney Failure by Angiotensinogen Inactivation in the Germline.

Background: Autosomal recessive renal tubular dysgenesis is a rare, usually fatal inherited disorder of the renin-angiotensis system (RAS). Herein, we report an adolescent individual experiencing an unknown chronic kidney disease and aim to provide novel insights into disease mechanisms.

Methods: Exome sequencing for a gene panel associated with renal disease was performed.

Early and Late Aortic-Related Mortality and Rupture After Fenestrated-Branched Endovascular Aortic Repair of Thoracoabdominal Aortic Aneurysms: A Prospective Multicenter Cohort Study.

Background: Fenestrated-branched endovascular aortic repair (FB-EVAR) has been used as a minimally invasive alternative to open surgical repair to treat patients with thoracoabdominal aortic aneurysms (TAAAs). The aim of this study was to evaluate aortic-related mortality (ARM) and aortic aneurysm rupture after FB-EVAR of TAAAs.

Methods: Patients enrolled in 8 prospective, nonrandomized, physician-sponsored investigational device exemption studies between 2005 and 2020 who underwent elective FB-EVAR of asymptomatic intact TAAAs were analyzed.

Activation of recombinases at specific DNA loci by zinc-finger domain insertions.

Recombinases have several potential advantages as genome editing tools compared to nucleases and other editing enzymes, but the process of engineering them to efficiently recombine predetermined DNA targets demands considerable investment of time and labor. Here we sought to harness zinc-finger DNA-binding domains (ZFDs) to program recombinase binding by developing fusions, in which ZFDs are inserted into recombinase coding sequences. By screening libraries of hybrid proteins, we optimized the insertion site, linker length, spacing and ZFD orientation and generated Cre-type recombinases that remain dormant unless the insertionally fused ZFD binds its target site placed in the vicinity of the recombinase binding site.

Dynamic Imaging of Blood Coagulation Within the Hematoma of Patients With Acute Hemorrhagic Stroke.

Background: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making.

Methods: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons.

Serial Lift-Out: sampling the molecular anatomy of whole organisms.

Cryo-focused ion beam milling of frozen-hydrated cells and subsequent cryo-electron tomography (cryo-ET) has enabled the structural elucidation of macromolecular complexes directly inside cells. Application of the technique to multicellular organisms and tissues, however, is still limited by sample preparation. While high-pressure freezing enables the vitrification of thicker samples, it prolongs subsequent preparation due to increased thinning times and the need for extraction procedures.

Cardiovascular risk due to diabetes mellitus in patients with chronic kidney disease-prospective data from the German Chronic Kidney Disease cohort.

Background: Diabetes mellitus (DM) and chronic kidney disease (CKD) are well-known cardiovascular and mortality risk factors. To what extent they act in an additive manner and whether the etiology of CKD modifies the risk is uncertain.

Methods: The multicenter, prospective, observational German Chronic Kidney Disease study comprises 5217 participants (1868 with DM) with a baseline mean estimated glomerular filtration rate of 30-60 mL/min/1.

Outcomes of Elective and Non-elective Fenestrated-branched Endovascular Aortic Repair for Treatment of Thoracoabdominal Aortic Aneurysms.

Objective: To describe outcomes after elective and non-elective fenestrated-branched endovascular aortic repair (FB-EVAR) for thoracoabdominal aortic aneurysms (TAAAs).

Background: FB-EVAR has been increasingly utilized to treat TAAAs; however, outcomes after non-elective versus elective repair are not well described.

Methods: Clinical data of consecutive patients undergoing FB-EVAR for TAAAs at 24 centers (2006-2021) were reviewed.

Depression and Anxiety as Predictors of Metabolic and Bariatric Surgery Completion Among Ethnically Diverse Patients.

Background: Mental health conditions including depression and anxiety are often prevalent among metabolic and bariatric surgery (MBS) patients, but it is not known if these conditions predict the decision to complete the procedure and if this varies by race and ethnicity. This study aimed to determine if depression and anxiety are associated with MBS completion among a race/ethnically diverse sample of patients.

Methods: This prospective cohort study included participants who were referred to an obesity program or two MBS practices between August 2019 and October 2022.

The influence of liver transplantation on the interplay between gut microbiome and bile acid homeostasis in children with biliary atresia.

Background: Biliary atresia (BA) causes neonatal cholestasis and rapidly progresses into cirrhosis if left untreated. Kasai portoenterostomy may delay cirrhosis. BA remains among the most common indications for liver transplantation (LT) during childhood.

Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults.

Background: Respiratory syncytial virus (RSV) infection causes considerable illness in older adults. The efficacy and safety of an investigational bivalent RSV prefusion F protein-based (RSVpreF) vaccine in this population are unknown.

Methods: In this ongoing, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults (≥60 years of age) to receive a single intramuscular injection of RSVpreF vaccine at a dose of 120 μg (RSV subgroups A and B, 60 μg each) or placebo.

Transient elastography and controlled attenuation parameter to evaluate hepatic steatosis and liver stiffness in postpartum patients.

Introduction: Nonalcoholic fatty liver disease (NAFLD) affects 30% of adults in the United States. Transient elastography (TE) (Fibroscan, Echosens, Paris, France) with controlled attenuation parameter (CAP) is a noninvasive way to evaluate liver steatosis and liver stiffness. The primary objective of this study was to assess prevalence of elevated liver stiffness and steatosis immediately postpartum.

Precise excision of HTLV-1 provirus with a designer-recombinase.

The human T cell leukemia virus type 1 (HTLV-1) is a pathogenic retrovirus that persists as a provirus in the genome of infected cells and can lead to adult T cell leukemia (ATL). Worldwide, more than 10 million people are infected and approximately 5% of these individuals will develop ATL, a highly aggressive cancer that is currently incurable. In the last years, genome editing tools have emerged as promising antiviral agents.

SUSTAINED BIWEEKLY AFLIBERCEPT FOR REFRACTORY NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The Prospective TRISTAR Study.

Purpose: To assess the safety and efficacy of biweekly (every 2 weeks) intravitreal aflibercept injections (IAI) 2 mg in eyes with refractory neovascular age-related macular degeneration (NVAMD).

Methods: A prospective, single-arm, interventional study was conducted. Eyes with refractory NVAMD received six biweekly IAIs through week 12, followed by a 4-week treatment pause until week 16.

Effect of 5 weeks of oral acetazolamide on patients with pulmonary vascular disease: A randomized, double-blind, cross-over trial.

Background: The carbonic anhydrase inhibitor acetazolamide stimulates ventilation through metabolic acidosis mediated by renal bicarbonate excretion. In animal models, acetazolamide attenuates acute hypoxia-induced pulmonary hypertension (PH), but its efficacy in treating patients with PH due to pulmonary vascular disease (PVD) is unknown.

Methods: 28 PVD patients (15 pulmonary arterial hypertension, 13 distal chronic thromboembolic PH), 13 women, mean±SD age 61.

Evolutionary history of transformation from chronic lymphocytic leukemia to Richter syndrome.

Richter syndrome (RS) arising from chronic lymphocytic leukemia (CLL) exemplifies an aggressive malignancy that develops from an indolent neoplasm. To decipher the genetics underlying this transformation, we computationally deconvoluted admixtures of CLL and RS cells from 52 patients with RS, evaluating paired CLL-RS whole-exome sequencing data. We discovered RS-specific somatic driver mutations (including IRF2BP2, SRSF1, B2M, DNMT3A and CCND3), recurrent copy-number alterations beyond del(9p21)(CDKN2A/B), whole-genome duplication and chromothripsis, which were confirmed in 45 independent RS cases and in an external set of RS whole genomes.

Clinical Outcomes and Quantitative Margin Analysis of a Universal Adhesive Using a Randomized Clinical Trial over Three Years.

The effectiveness of a universal adhesive applied in different application modes for the preparation of Class V composite restorations was evaluated both clinically and by quantitative marginal analysis (QMA). In each of the 22 patients, four non-carious cervical lesions (NCCL) were restored with Filtek Supreme XTE (3M). The adhesive Scotchbond Universal (SBU, 3M) was applied in self-etch (SE), selective-enamel-etch (SEE) or etch-and-rinse (ER) modes.

Involvement of Thalamocortical Networks in Patients With Poststroke Thalamic Aphasia.

Background And Objective: Theories assume that thalamic stroke may cause aphasia because of dysfunction in connected cortical networks. This takes into account that brain functions are organized in distributed networks, and in turn, localized damage may result in a network disorder such as thalamic aphasia. With this study, we investigate whether the integration of the thalamus into specific thalamocortical networks underlies symptoms after thalamic stroke.

A Remote Longitudinal Observational Study of Individuals at Genetic Risk for Parkinson Disease: Baseline Results.

Background And Objectives: To recruit and characterize a national cohort of individuals who have a genetic variant ( G2019S) that increases risk of Parkinson disease (PD), assess participant satisfaction with a decentralized, remote research model, and evaluate interest in future clinical trials.

Methods: In partnership with 23andMe, Inc., a personal genetics company, G2019S carriers with and without PD were recruited to participate in an ongoing 36-month decentralized, remote natural history study.

Establishment of a Tissue-Mimicking Surrogate for Pulmonary Lesions to Improve the Development of RFA Instruments and Algorithms.

(1) Development of radiofrequency ablation (RFA) systems for pulmonary lesions is restricted by availability of human tumor specimens and limited comparability of animal tissue. We aimed to develop a new surrogate tissue overcoming these drawbacks. (2) Reference values for electrical impedance in lung tumor tissue were collected during routine lung tumor RFA (n = 10).

Progranulin mutations in clinical and neuropathological Alzheimer's disease.

Introduction: Progranulin (GRN) mutations occur in frontotemporal lobar degeneration (FTLD) and in Alzheimer's disease (AD), often with TDP-43 pathology.

Methods: We determined the frequency of rs5848 and rare, pathogenic GRN mutations in two autopsy and one family cohort. We compared Braak stage, β-amyloid load, hyperphosphorylated tau (PHFtau) tangle density and TDP-43 pathology in GRN carriers and non-carriers.