Multicenter validation of an RNA-based assay to predict anti-PD-1 disease control in patients with recurrent or metastatic head and neck squamous cell carcinoma: the PREDAPT study.

Background: Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients.

Using Tumor-Informed Circulating Tumor DNA (ctDNA)-Based Testing for Patients with Anal Squamous Cell Carcinoma.

Background: Anal squamous cell carcinoma (SCCA) is an uncommon malignancy with a rising incidence that has a high cure rate in its early stages. There is an unmet need for a reliable method to monitor response to treatment and assist in surveillance. Circulating tumor DNA (ctDNA) testing has shown great promise in other solid tumors for monitoring disease progression and detecting relapse in real time.

Detection of microsatellite instability high (MSI-H) status by targeted plasma-based genotyping in metastatic breast cancer.

We evaluate microsatellite instability-high (MSI-H) status with cell-free DNA (cfDNA) in metastatic breast cancer (MBC) and the association with clinico-genomic characteristics. Patients with MSI-H in cfDNA (Guardant360, 74 gene next-generation sequencing (NGS) with MBC are identified. We conduct a retrospective review.

Treatment Response Monitoring Using a Tumor-Informed Circulating Tumor DNA Test in an Advanced Triple-Negative Breast Cancer Patient: A Case Report.

Triple-negative breast cancer (TNBC) is highly aggressive disease that is often refractory to surgery and multiple lines of therapy. Although the repertoire of FDA-approved treatments has expanded, there is an unmet need for biomarkers that can aid in appropriate selection and timing of therapy. We present a case of highly aggressive treatment-resistant TNBC that employed a comprehensive genomic profiling (CGP)-based assay to identify therapeutic targets, followed by longitudinal circulating tumor DNA (ctDNA) testing.

Prevalence of HIV and other sexually transmitted infections and their association with sexual practices and substance use among 2238 MSM in Lebanon.

UNAIDS report documents 95% increase in new HIV infections among key populations in Eastern Europe and Middle East and North Africa region. Data on HIV and STIs among MSM in Lebanon is still scarce. Therefore, the aim was to assess prevalence of HIV and sexually transmitted infections (STIs) among men who have sex with men (MSM) in Lebanon and associations with sexual practices and substance-use.

Validation of Microsatellite Instability Detection Using a Comprehensive Plasma-Based Genotyping Panel.

Purpose: To analytically and clinically validate microsatellite instability (MSI) detection using cell-free DNA (cfDNA) sequencing.

Experimental Design: Pan-cancer MSI detection using Guardant360 was analytically validated according to established guidelines and clinically validated using 1,145 cfDNA samples for which tissue MSI status based on standard-of-care tissue testing was available. The landscape of cfDNA-based MSI across solid tumor types was investigated in a cohort of 28,459 clinical plasma samples.

Safety of tiotropium Respimat in black or African-American patients with symptomatic asthma.

Background: Black patients with asthma have a higher disease burden and greater morbidity compared with other racial/ethnic groups. Tiotropium Respimat, as add-on to at least inhaled corticosteroids (ICS), improves lung function and asthma control and reduces asthma exacerbation risk in patients, with a safety profile comparable with placebo. This study aimed to assess the safety of tiotropium Respimat, compared with placebo, in black or African-American patients.

Tiotropium add-on therapy is safe and reduces seasonal worsening in paediatric asthma patients.

There remains an unmet need for effective, well-tolerated therapeutic options in paediatric patients with not fully controlled asthma, for whom safety is of paramount importance.Data were pooled from five randomised, double-blind, placebo-controlled studies evaluating tiotropium 5 or 2.5 µg placebo add-on therapy in patients with symptomatic asthma aged 1-17 years.

In vitro and clinical characterization of the valved holding chamber AeroChamber Plus Flow-Vu for administrating tiotropium Respimat in 1-5-year-old children with persistent asthmatic symptoms.

Background: When characterizing inhalation products, a comprehensive assessment including in vitro, pharmacokinetic (PK), and clinical data is required. We conducted a characterization of tiotropium Respimat when administered with AeroChamber Plus Flow-Vu anti-static valved holding chamber (test VHC) with face mask in 1-5-year-olds with persistent asthmatic symptoms.

Methods: In vitro tiotropium dose and particle size distribution delivered into a cascade impactor were evaluated under fixed paediatric and adult flow rates between actuation and samplings.

Safety and efficacy of tiotropium in children aged 1-5 years with persistent asthmatic symptoms: a randomised, double-blind, placebo-controlled trial.

Background: Few studies have assessed the safety and efficacy of potential asthma medications in children younger than 5 years. We descriptively assessed the safety and efficacy of tiotropium, a long-acting anticholinergic drug, in children aged 1-5 years with persistent asthmatic symptoms.

Methods: This exploratory 12-week, randomised, double-blind, placebo-controlled, parallel-group, phase 2/3, regulatory multicentre trial was done at 32 hospitals, clinics, and clinical research units in 11 countries in Asia, Europe, and North America.

A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma.

Background: Studies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICSs) with or without other maintenance therapies in patients with moderate or severe symptomatic asthma.

Objective: We sought to assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma.

Methods: In this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6 to 11 years were randomized to receive once-daily tiotropium 5 μg (2 puffs of 2.

Novel carbocyclic nucleoside analogs suppress glomerular mesangial cells proliferation and matrix protein accumulation through ROS-dependent mechanism in the diabetic milieu. II. Acylhydrazone-functionalized pyrimidines.

We report herein the synthesis of a novel series of carbocyclic acylhydrazone derivatives of uracil, thymine and cytosine from the corresponding nucleic bases and their biological activity to treat diabetic nephropathy. Intriguingly, five derivatives significantly reduced high-glucose induced glomerular mesangial cells proliferation and matrix protein accumulation in vitro. The anti-oxidative effects displayed by these molecules suggest that their activity might involve a ROS-dependent mechanism.

Hypovitaminosis D in a Young Lebanese Population: Effect of GC Gene Polymorphisms on Vitamin D and Vitamin D Binding Protein Levels.

Bioactive vitamin D is a steroid hormone transported in blood via the vitamin D binding protein (DBP). Our study aimed to investigate the vitamin D status in a young Lebanese population and study the association of hypovitaminosis with levels of DBP. Polymorphisms in the GC gene that encodes DBP were also screened.

Isocitrate dehydrogenase mutations in chondrosarcoma: the crossroads between cellular metabolism and oncogenesis.

Purpose Of Review: This article reviews the most recent developments and implications in regard to isocitrate dehydrogenase mutations in chondrosarcoma, a disease in which currently available systemic therapies have proven inefficacious, with an emphasis on how disruption in normal cellular metabolism plays a role in oncogenesis.

Recent Findings: The development of acquired isocitrate dehydrogenase-1/isocitrate dehydrogenase-2 mutations has been described in multiple tumors and more recently in chondrosarcomas. The impact of these mutations has been the focus of multiple research efforts during the last years, allowing us to better understand the impact of the mutation, including its interaction with other proteins, changes in expression of genes involved in tumor genesis, the oncogenic potential of 2-hydroxyglutarate, the impact on cellular proliferation and differentiation, and the influence on the epigenetic state of cells owing to changes in DNA and histone methylation patterns.

Effects of proton pump inhibitors and electrolyte disturbances on arrhythmias.

Several case reports have been written regarding the relationship between the use of proton pump inhibitors (PPI) and hypomagnesemia. Some of these reported cases have electrocardiogram abnormalities where electrolytes deficiencies were the contributing factor for these events. This study investigates the correlation between different arrhythmias and the use of PPI and hypomagnesaemia incidence.

Congestive heart failure risk in patients with breast cancer treated with bevacizumab.

Purpose: Bevacizumab is a treatment option in patients with metastatic breast cancer. Congestive heart failure (CHF) has been reported, although the overall incidence and relative risk (RR) of this complication remains unclear. We performed an up-to-date, comprehensive meta-analysis to determine the risk of serious CHF in patients with breast cancer receiving bevacizumab.