Patient activation

AIM: Aortic aneurysms (AA) frequently involve dysregulation of transforming growth factor β (TGF-β)-signaling in the aorta. Here, FURIN was tested as aneurysm predisposition gene given its role as proprotein convertase in pro-TGF-β maturation. METHODS AND RESULTS: Rare FURIN variants were detected by whole-exome sequencing of 781 unrelated aortic aneurysm patients and affected relatives. Thirteen rare heterozygous FURIN variants occurred in 3.7% (29) unrelated index AA patients, of which 72% had multiple aneurysms or a dissection...

CONTEXT: The enterohepatic circulation of bile acids depends on intestinal absorption by bile acid transporters and activation of bile acid receptors, which stimulates secretion of hormones regulating glucose and lipid metabolism and appetite. Distribution of bile acid transporters and receptors in the human gut and their potential involvement in type 2 diabetes (T2D) pathophysiology remain unknown. OBJECTIVE: We explored the expression of genes involved in bile acid metabolism throughout the intestines of patients with T2D and matched healthy controls...

PURPOSE: The multicenter, open-label, randomized phase 2 NCI-9944 study (NCT02595892) demonstrated that addition of ATR inhibitor (ATRi) berzosertib to gemcitabine increased progression-free survival (PFS) compared to gemcitabine alone (hazard ratio [HR]=0.57, one-sided log-rank P = .044, which met the one-sided significance level of 0.1 used for sample size calculation). METHODS: We report here the final overall survival (OS) analysis and biomarker correlations (ATM expression by immunohistochemistry, mutational signature 3 and a genomic biomarker of replication stress) along with post-hoc exploratory analyses to adjust for crossover from gemcitabine to gemcitabine/berzosertib...

PURPOSE: Few studies have explored the potential for pharmacological interventions to delay disease progression in patients undergoing active surveillance (AS). This preplanned transcriptomic analysis of patient samples from the ENACT trial aims to identify biomarkers in patients on AS who are at increased risk for disease progression or who may derive the greatest benefit from enzalutamide treatment. PATIENTS AND METHODS: In the phase II ENACT (ClinicalTrials.gov identifier: NCT02799745) trial, patients on AS were randomly assigned 1:1 to 160 mg orally once daily enzalutamide monotherapy or continued AS for 1 year...

BACKGROUND: Myoelectric prostheses have become the accepted standard of care for pediatric upper-limb amputees. OBJECTIVES: To describe the clinical characteristics and patterns of prosthesis use and to analyze the changes that occur during the growth process of these patients. STUDY DESIGN: This is a longitudinal retrospective study comparing the results of surveys carried out in 2015 and 2022. METHODS: The variables measured included clinical and demographic characteristics, patterns of use, and satisfaction with the prosthesis...

Recurrent abnormalities in immune surveillance-related genes affect the progression of diffuse large B-cell lymphoma (DLBCL) and modulate the response to therapeutic interventions. CD58 interacts with the CD2 receptor on T cells and natural killer (NK) cells and is recurrently mutated and deleted in DLBCL, suggesting it may play a role in regulating antitumor immunity. Herein, we comprehensively analyzed the genomic characteristics of CD58 through targeted next-generation sequencing, RNA-sequencing, whole-exome sequencing, and single-cell RNA-sequencing in patients with newly diagnosed DLBCL...

TIGIT is an inhibitory receptor on immune cells that outcompetes an activating receptor, CD226, for shared ligands. Tumor-infiltrating lymphocytes express TIGIT and CD226 on regulatory T cells (Treg) and on CD8+ T cells with tumor-reactive or exhausted phenotypes, supporting the potential of therapeutically targeting TIGIT to enhance anti-tumor immunity. To optimize the efficacy of therapeutic antibodies against TIGIT, it is necessary to understand whether there is therapeutic benefit from Fcγ receptor (FcγR) binding...

The primary objectives of any high-volume surgery department should be patient safety, block time utilization and operating room efficiency. Reducing preparation time in the OR prior to actual surgery can improve operating room efficiency and utilization, but only if patient safety can be maintained. With this goal, this study evaluated a novel skin preparation technique using a device named ULTRAPREP™, a sterile, medical-grade plastic bag that is applied to the upper or lower extremity in the pre-operative holding area which allows for skin disinfection outside the OR (referred to as "disinfection bag")...

Metabolic subtypes of glioblastoma have different prognoses and responses to treatment. Deuterium metabolic imaging with 2H-labeled substrates is a potential approach to stratify patients into metabolic subtypes for targeted treatment. Here, we used 2H magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) measurements of [6,6'-2H2]glucose metabolism to identify metabolic subtypes and their responses to chemoradiotherapy in patient-derived glioblastoma xenografts in vivo. The metabolism of patient-derived cells was first characterized in vitro by measuring the oxygen consumption rate, a marker of mitochondrial TCA cycle activity, as well as the extracellular acidification rate and 2H-labeled lactate production from [6,6'-2H2]glucose, which are markers of glycolytic activity...

Oncogenic KRAS impairs anti-tumor immune responses. As effective strategies to combine KRAS inhibitors and immunotherapies have so far proven elusive, a better understanding of how oncogenic KRAS drives immune evasion is needed to identify approaches that could sensitize KRAS-mutant lung cancer to immunotherapy. In vivo CRISPR-Cas9 screening in an immunogenic murine lung cancer model identified mechanisms by which oncogenic KRAS promotes immune evasion, most notably via upregulation of immunosuppressive cyclooxygenase-2 (COX-2) in cancer cells...

To mitigate the loss of lives during the COVID-19 pandemic, emergency use authorization was given to several anti-SARS-CoV-2 monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in patients with a high risk of progressing to severe disease. Monoclonal antibodies used to treat SARS-CoV-2 target the spike protein of the virus and block its ability to enter and infect target cells. Monoclonal antibody therapy can thus accelerate the decline in viral load and lower hospitalization rates among high-risk patients with variants susceptible to mAb therapy...

CASE: We describe the unique case of a 20-year-old man with a history of Legg-Calve-Perthes disease, hip dysplasia, and osteochondral fragmentation of the medial femoral head. We performed arthroscopic femoroplasty and femoral head allografting, followed by a valgus-producing derotational femoral osteotomy (DFO) and periacetabular osteotomy (PAO). At 1-year follow-up, the patient achieved osseous union and complete femoral head healing with return to his active hobbies. CONCLUSION: We describe the successful utilization of arthroscopic allografting for medial femoral head osteochondral fragmentation...

» Osteochondritis dissecans of the capitellum is a localized compromise of bone that may lead to subchondral collapse with articular cartilage damage and loose body formation.» The etiology is multifactorial; proposed mechanisms include repetitive microtrauma, vascular insufficiency, and genetic predisposition.» Diagnosis is based on patient presentation, clinical examination, diagnostic imaging, and intraoperative findings.» Management is dependent on lesion characteristics, with stable lesions amenable to nonoperative treatment and unstable lesions managed with surgical intervention...

Sarcopenia prevalence and its risk factors in chronic obstructive pulmonary disease (COPD) vary partly due to definition criteria. This systematic review aimed to identify the prevalence and risk factors of sarcopenia in COPD patients. This review was registered in PROSPERO (CRD42022310750). Nine electronic databases were searched from inception to September 1st, 2022, and studies related to sarcopenia and COPD were identified. Study quality was assessed using a validated scale matched to study designs, and a meta-analysis was performed to evaluate sarcopenia prevalence...

AIMS: This study investigated whether an activated R-mode in patients carrying a cardiac implantable electronic device (CIED) is associated with worse prognosis during and after an episode of acutely decompensated heart failure (AHF). METHODS: Six hundred and twenty-three patients participating in an ongoing prospective cohort study that phenotypes and follows patients admitted for AHF were studied. We compared CIED carriers with activated R-mode stimulation (CIED-R) to CIED carriers not in R-mode (CIED-0) and patients without CIEDs (no-CIED)...

BACKGROUND: Faced with the increase in the number of chronic diseases with the aging of the population, and with the observation of the insufficiency of therapeutic control, a new need has emerged, that of having a patient as a partner in care. METHODS: This study is a randomized controlled trial. Patients with coronary heart disease will be recruited from one clinical site and randomly assigned into two groups: the intervention group and the control group. All participants will be followed up for a total of one year (with three-time points for data collection)...

BACKGROUND: The use of routinely collected health data for secondary research purposes is increasingly recognised as a methodology that advances medical research, improves patient outcomes, and guides policy. This secondary data, as found in electronic medical records (EMRs), can be optimised through conversion into a uniform data structure to enable analysis alongside other comparable health metric datasets. This can be achieved with the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM), which employs a standardised vocabulary to facilitate systematic analysis across various observational databases...

BACKGROUND: In traumatic brain injury patients (TBI) admitted to the intensive care unit (ICU), agitation can lead to accidental removal of catheters, devices as well as self-extubation and falls. Actigraphy could be a potential tool to continuously monitor agitation. The objectives of this study were to assess the feasibility of monitoring agitation with actigraphs and to compare activity levels in agitated and non-agitated critically ill TBI patients. METHODS: Actigraphs were placed on patients' wrists; 24-hour monitoring was continued until ICU discharge or limitation of therapeutic efforts...

PURPOSE: The diagnosis of conjunctival squamous intraepithelial neoplasia (CSIN) can be difficult because of the heterogeneous appearance. Despite established risk factors and diagnostic support by high-resolution optical coherence tomography (hrOCT) and indocyanine green angiography (ICGA), the only reliable diagnostic method is a histological work-up. This case report is the first to describe corneal microaneurysms in CSIN as a vascular feature for conjunctival tumor angiogenesis. METHODS: An 84-year-old male patient was referred with a suspected diagnosis of pterygium...

OBJECTIVE: This systematic review aimed to analyse the effect of early weight bearing versus late weight bearing on rehabilitation outcomes after ankle fractures, which primarily include ankle function scores, time to return to work/daily life and complication rates. METHODS: The China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Science and Technology Journal, Web of Science, PubMed, Embase and Cochrane Library databases were searched...