Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease for which current treatment options only slow clinical progression. Previously, we identified a subset of patients with IPF with an accelerated disease course associated with fibroblast expression of Toll-Like Receptor 9 (TLR9) mediated by interactions with its ligand mitochondrial DNA (mtDNA).

Objectives: We aimed to show that TLR9 activation induces fibroproliferative responses that are abrogated by its antagonism by using two commercially-available indirect inhibitors and a proprietary, selective direct small molecule inhibitor.

Assessing the Impact of a Designated Pharmacist Intervention on Drug Treatment Costs and Technical Efficiency in the Hemato-Oncology Outpatient Clinic.

Objectives: This study aimed to investigate the impact of a designated pharmacist (DPha) intervention in a hemato-oncology unit, focusing on reducing drug treatment costs and improving technical efficiency (TE).

Methods: Data from an 8-month intervention in the Israeli Clalit Health Services hemato-oncology outpatient unit were analyzed. During the study, the DPha reviewed the drug therapies being administered.

Efficacy and safety of SENS-401 in sudden sensorineural hearing loss: The AUDIBLE-S randomized placebo-controlled phase IIb trial.

Purpose: Safety and efficacy of SENS-401, a serotonin type 3 (5-HT) receptor antagonist and calcineurin inhibitor, in patients with acute sudden sensorineural hearing loss (SSNHL).

Methods: Multicentre randomized, double blind, placebo-controlled trial enrolled adult subjects with sudden sensorineural hearing loss (SSNHL) or unilateral/bilateral acute acoustic trauma leading to SSNHL within 96 h of disease onset. Subjects were randomly assigned to one of the three oral dose groups: 29 mg, 43.

Characteristics, management and outcome of patients with late-arrival STEMI in the Acute Coronary Syndrome Israeli Surveys (ACSIS).

Introduction: Patients with ST-elevation myocardial infarction (STEMI) and late arrival (>12 h) after symptom onset, are at high risk for mortality and heart failure and represent a challenge for management. We aimed to define patient characteristics, management, and outcome of late-arrival STEMI in Israel over the last 20 years.

Methods: We analyzed data of late-arrival STEMI (12-48 h and > 48 h) from the biennial acute coronary syndrome Israeli Surveys (ACSIS), as well as time-dependent changes [early (2000-2010) Vs.

E148Q variant: a familial Mediterranean fever-causing mutation or a sequence variant?

Unlabelled: Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease, linked to mutations in the MEFV gene. The p.E148Q variant, found on exon 2, has an uncertain role in FMF, with debates on whether it is a benign polymorphism or a pathogenic mutation.

Efficacy, adherence and persistence of various glucagon-like peptide-1 agonists: nationwide real-life data.

Aim: The management of type 2 diabetes mellitus has advanced in the last two decades since the introduction of glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, multiple factors may interfere with achieving better glycaemic control. This study evaluated the differences between various GLP-1RAs in efficacy, adherence and persistence.

Methodology and challenges for harmonization of nutritional data from seven historical studies.

Background: Collection of detailed dietary data is labor intensive and expensive, harmonization of existing data sets has been proposed as an effective tool for research questions in which individual studies are underpowered.

Methods: In this paper, we describe the methodology used to retrospectively harmonize nutritional data from multiple sources, based on the individual participant data of all available studies, which collected nutritional data in Israel between 1963 and 2014. This collaboration was established in order to study the association of red and processed meat with colorectal cancer.

Reversed halo sign as a radiological feature of tuberculosis - Report of two cases.

Reversed halo sign (RHS) is a radiological feature described as a focal, rounded area of ground-glass opacity surrounded by a ring of consolidation. In this report we describe two unique radiological cases demonstrating diffuse bilateral infiltrates with multiple RHSs in chest CT scans. Both patients were ultimately diagnosed as having tuberculosis (TB) and had been exposed to silica in the past.

The value of routine hemoglobin level evaluation following elective cesarean section: Is it worthwhile?

Objective: The aim of this study was to assess the usefulness of routine hemoglobin testing following elective and urgent cesarean section (CS) in patients without primary postpartum hemorrhage (PPH).

Methods: This retrospective cohort study included women who underwent vaginal delivery (VD), elective CS, and urgent CS at Carmel Medical Center from 2015 to 2020. Data were extracted from the obstetric database, excluding deliveries with PPH.

Clinical outcomes of immunomodulation therapy in immunocompromised patients with severe Covid-19 and high oxygen requirement.

Covid-19 disease is implicated in increased mortality among immunocompromised patients. The JAK inhibitor, baricitinib (bar), or the IL-6 inhibitor, tocilizumab (toc), demonstrated a survival benefit in patients with severe disease.However, evidence supporting their use in immunocompromised patients with severe Covid-19 is scarce.

A historical cohort study with 27,754 individuals on the association between meat consumption and gastrointestinal tract and colorectal cancer incidence.

In order to explore the association between meat consumption and gastrointestinal/colorectal cancer (CRC) risk and to estimate the Israeli population attributable fraction (PAF), we conducted a collaborative historical cohort study using the individual participant data of seven nutritional studies from the past 6 decades. We included healthy adult men and women who underwent a nutritional interview. Dietary assessment data, using food-frequency or 24-h recall questionnaires, were harmonized.

Association of Acute Incidental Cerebral Microinfarcts With Subsequent Ischemic Stroke in Patients With Cancer: A Population-Based Study.

Background And Objectives: Incidental diffuse-weighted imaging (DWI)-positive subcortical and cortical lesions, or acute incidental cerebral microinfarcts (CMIs), are a common type of brain ischemia, which can be detected on magnetic resonance DWI for approximately 2 weeks after occurrence. Acute incidental CMI was found to be more common in patients with cancer. Whether acute incidental CMI predicts future ischemic stroke is still unknown.

Phosphodiesterase-5 Inhibitors and Dementia Risk: A Real-World Study.

Introduction: Biological and scarce epidemiological evidence suggested that phosphodiesterase-5 inhibitors (PDE5i) might reduce dementia risk. We aimed to examine the association between PDE5i and dementia using real-world data.

Methods: Two retrospective cohorts within the database of Clalit, the largest healthcare provider in Israel (2005-2023), were studied.

Vericiguat and Cardiovascular Outcomes in Heart Failure by Baseline Diabetes Status: Insights From the VICTORIA Trial.

Background: Type 2 diabetes mellitus (T2DM) significantly worsens heart failure (HF) prognosis.

Objectives: This study sought to investigate the impact of T2DM on outcomes in patients enrolled in VICTORIA and assess the efficacy of vericiguat in patients with and without T2DM.

Methods: Patients with HF with reduced ejection fraction were randomized to receive vericiguat or placebo in addition to standard therapy.

Lipid-lowering therapy with inclisiran in the real-world setting: Initial data from a national health care service.

Background: Inclisiran, a small-interfering RNA enabling long-term inhibition of proprotein convertase subtilisin kexin type 9 (PCSK9) synthesis, demonstrates a good safety and efficacy profile in clinical trials. Real-world data on the potential to attain lipid-goals and reduce treatment gaps are lacking.

Objectives: To investigate the implementation of inclisiran in real-world clinical setting.

Is infertility more common among patients with multiple sclerosis? Implications for utilization of assisted reproductive techniques.

Research Question: Is fertility affected in women with multiple sclerosis (MS), and what is their usage of assisted reproductive technology (ART)?

Design: Data regarding multiple sclerosis and ART usage among patients with multiple sclerosis were extracted from the Israeli health maintenance organization Clalit Health Service database. Data regarding the diagnosis and treatment of multiple sclerosis, cause of infertility and use of fertility treatments were collected for all female multiple sclerosis patients aged 18-45 years between 2005 and 2021. Each patient was matched by age in a 1:10 ratio with reference women from the general population.

Varicella-Zoster Virus-Induced Neurologic Disease After COVID-19 Vaccination: A Multicenter Observational Cohort Study.

Background: Early reports described an increased risk of herpes zoster following receipt of mRNA-based COVID-19 vaccines. The objective was to assess whether COVID-19 vaccine is associated with varicella-zoster virus-induced neurologic disease (VZV-ND).

Methods: This multicenter retrospective case-control study with a test-negative design was conducted at 12 hospitals in Israel.

De-escalation of Disease-Modifying Therapy for People with Multiple Sclerosis Due to Safety Considerations: Characterizing 1-Year Outcomes in 25 People Who Switched from Ocrelizumab to Diroximel Fumarate.

Introduction: Switching disease-modifying therapy (DMT) may be considered for relapsing-remitting multiple sclerosis (RRMS) if a patient's current therapy is no longer optimal. This was particularly important during the recent COVID-19 pandemic because of considerations around immune deficiency and impaired vaccine response associated with B cell-depleting DMTs. This real-world, single-center study aimed to evaluate change or decline in functional ability and overall disease stability in people with RRMS who were switched from B cell-depleting ocrelizumab (OCRE) to diroximel fumarate (DRF) because of safety concern related to the COVID-19 pandemic.

Medications and Acute Hemolysis in G6PD-Deficient Patients - A Real-World Study.

Many drug labels contain precautions of use in G6PD-deficient patients due to hemolytic concerns, but much of this is based on scarce clinical, epidemiological, or structural data. In this real-world study, we aimed to examine if the administration of presumably risky medications for G6PD-deficient patients was followed by hemolysis. The study is based on data from Clalit Health Services database that provides inclusive health care for more than half of the Israeli population (~ 4.