MET alterations in advanced non-small cell lung cancer.

Precision medicine has helped identify several tumor molecular aberrations to be treated with targeted therapies. These therapies showed substantial improvement in efficacy without excessive toxicity in patients with specific oncogenic drivers with advanced cancers. In metastatic lung cancers, the implementation of broad platforms for molecular tumor sequencing has helped oncology providers identify oncogenic drivers linked with better outcomes when treated upfront with targeted therapies.

A Phase 1/2 Study to Evaluate the Safety and Activity of Nivolumab in Combination With Vorolanib, a Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitor, in Patients With Refractory Thoracic Tumors.

Introduction: Targeting the tumor microenvironment may enhance response to immunotherapy (immune checkpoint inhibitors) and improve outcomes for patients. This study tested the safety and efficacy of vorolanib, a novel tyrosine kinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and c-KIT, in combination with programmed cell death protein 1 blockade using nivolumab for refractory thoracic malignancies.

Methods: This single-arm multicenter study enrolled patients with extensive-stage SCLC, thymic carcinoma, and NSCLC, either naive or had progressed on previous chemotherapy or immune checkpoint inhibitors (either primary or acquired resistance).

A Phase 2 Study of Docetaxel, Ramucirumab, and Pembrolizumab for Patients With Metastatic or Recurrent Non-Small-Cell Lung Cancer (NSCLC) who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade.

Background: There is an urgent and unmet need for more effective treatment options for patients with metastatic and recurrent non-small-cell lung cancer (NSCLC) who progressed on platinum-based therapy, immune checkpoint inhibitors (ICI), and targeted therapies. Currently, the combination of docetaxel (D) and ramucirumab (R) is the next best salvage therapy with a modest historical progression free survival (PFS) of 4.5 months and 6-month PFS rate of 37% predating the era of ICI use.

Novel targeted therapies for advanced non-small lung cancer.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer accounting for almost 80%-85% of all lung cancer cases. Unfortunately, more than half of the patients will be diagnosed with advanced disease at the time of presentation, which makes their disease incurable. Historically, the 5 year overall survival for advanced NSCLC was 5%.

Cough-induced rib fracture in a smoker: a case report.

Background: Coughing is considered an important mechanism that helps the body get rid of foreign substances or prevent their entry into the tracheobronchial tree. Infrequently, after the onset of coughing, patients presenting with persistent chest pain are found to have rib fractures. Among the cases reported for cough-induced rib fractures, the maximum number of fractured ribs was found to be four.

Fusion: Joining the Ranks of Targetable Molecular Drivers in NSCLC.

The era of precision medicine has resulted in the identification of a number of genomic alterations that can be targeted with novel therapies. In lung adenocarcinomas, a histology structure that accounts for nearly 50% of all cases of lung cancer, and a number of genomic targets have been linked with effective targeted therapies. For patients with advanced-stage lung adenocarcinomas, molecular testing is now a standard part of diagnostic workup; for patients that have specific driver molecular events, targeted therapies have resulted in substantial improvement in efficacy without excessive toxicity.

Correlations between serum inflammatory markers and comorbidities in patients with end-stage renal disease.

Objectives: Chronic inflammatory processes are common in patients with renal disease, especially those with end-stage renal disease (ESRD), in whom inflammatory markers have been shown to increase with renal function deterioration. ESRD is usually accompanied by other chronic diseases such as hypertension and diabetes. The relationships between ESRD comorbidities and serum levels of inflammatory markers have not yet been fully understood.

Uremic Serum Induces Inflammation in Cultured Human Endothelial Cells and Triggers Vascular Repair Mechanisms.

Inflammation and cardiovascular disease (CVD) are common in end-stage renal disease (ESRD) patients whose vascular endothelium is in direct contact with the uremic toxins found in the blood. These toxins are believed to affect vascular injury and repair process, which is impaired in ESRD patients. The exact mechanisms behind these interactions are not clear.

Characteristics and Outcomes of Patients With Metastatic KRAS-Mutant Lung Adenocarcinomas: The Lung Cancer Mutation Consortium Experience.

Introduction: Mutations in the KRAS gene are the most common driver oncogenes present in lung adenocarcinomas. We analyzed the largest multi-institutional database available containing patients with metastatic KRAS-mutant lung adenocarcinomas.

Methods: The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional collaboration to study the genomic characteristics of lung adenocarcinomas, treat them with genomically directed therapeutic approaches, and assess their outcomes.

Biochemical profile of non-enzymatic stress markers in the plant species "Urginea maritima" in a Mediterranean natural reserve exposed to oxidative stress.

Protected areas decrease degrading natural ecosystems due to pollution such as air pollution. In 1981, the inhabitants founded Bentael natural reserve in Byblos, Lebanon, to secure their region against urbanization projects, like the recently constructed road that threatens the biodiversity of the reserve. This study was conducted to determine the oxidative stress resulting from this pollution and that menaces 360 floral species among them a rare species "Urginea maritima.

Not all immune-checkpoint inhibitors are created equal: Meta-analysis and systematic review of immune-related adverse events in cancer trials.

Background: Targeting immune checkpoints is a novel approach in cancer therapy. This strategy may trigger immune related adverse events (irAE). We hypothesize that the incidence of irAE will be greater in patients receiving immune checkpoint inhibitors (ICI) targeting only immune cells compared to those that also target tumor cells (PD-L1).

Phase IB Study of Vemurafenib in Combination with Irinotecan and Cetuximab in Patients with Metastatic Colorectal Cancer with BRAFV600E Mutation.

Unlabelled: In vitro, EGFR inhibition, combined with the BRAF inhibitor vemurafenib, causes synergistic cytotoxicity for BRAF metastatic colorectal cancer, further augmented by irinotecan. The safety and efficacy of vemurafenib, irinotecan, and cetuximab in BRAF-mutated malignancies are not defined. In this 3+3 phase I study, patients with BRAF-advanced solid cancers received cetuximab and irinotecan with escalating doses of vemurafenib.

Innovative Strategies for Decreasing Blood Collection Wait Times for Patients in Early-Phase Cancer Clinical Trials.

Purpose: Long wait times are a primary source of dissatisfaction among patients enrolled in early-phase clinical trials. We hypothesized that an automated patient check-in system with readily available display for increasing awareness of waiting intervals would improve patient flow and use of our rooms, with decreased turnover time and increased throughput.

Methods: We recorded in-room wait times for patients seen in our clinic and observed the logistics involved in the blood collection process to delineate causes for delays.

Increased sensitivity of rheumatoid synoviocytes to Schnurri-3 expression in TNF-α and IL-17A induced osteoblastic differentiation.

Objective: To compare the effects of TNF-α and IL-17A on osteogenic differentiation of isolated fibroblast-like synoviocytes (FLS) from healthy donors, osteoarthritis (OA) and rheumatoid arthritis (RA) patients.

Methods: FLS were cultured in osteogenic medium, with and without TNF-α and/or IL-17A. Extracellular matrix mineralization was evaluated by alizarin red staining and alkaline phosphatase activity (ALP) measurement.

Differential Effects of IL-17A and TNF-α on Osteoblastic Differentiation of Isolated Synoviocytes and on Bone Explants from Arthritis Patients.

Objective: TNF-α and IL-17A act on fibroblast-like synoviocytes (FLS) and contribute to cytokine production, inflammation, and tissue destruction in rheumatoid arthritis (RA). The aim of this study was to compare their effects on osteogenic differentiation of isolated FLS and on whole bone explants from RA and osteoarthritis (OA) patients.

Methods: Fibroblast-like synoviocytes and bone explants were cultured in the presence or absence of TNF-α and/or IL-17A.

Bisphosphonate-related osteonecrosis of the jaw: awareness and level of knowledge of Lebanese physicians.

Purpose: Bisphosphonate-induced osteonecrosis of the jaw (ONJ) is a potentially destructive complication, particularly encountered in oncology. It is supposed that awareness and good knowledge of this disease by physicians are important factors of its early detection and management. This study aims to evaluate the level of knowledge among a sample of Lebanese physicians with regard to this complication.

Effects of Interleukin-17A on Osteogenic Differentiation of Isolated Human Mesenchymal Stem Cells.

Objectives: Rheumatoid arthritis (RA) is characterized by defective bone repair and excessive destruction and ankylosing spondylitis (AS) by increased ectopic bone formation with syndesmophytes. Since TNF-α and IL-17A are involved in both diseases, this study investigated their effects on the osteogenic differentiation of isolated human bone marrow-derived mesenchymal stem cells (hMSCs).

Methods: Differentiation of hMSCs into osteoblasts was induced in the presence or absence of IL-17A and/or TNF-α.

Classical and Paradoxical Effects of TNF-α on Bone Homeostasis.

Tumor necrosis factor-α (TNF-α) plays an essential role in the regulation of bone homeostasis in several chronic immune and inflammatory joint diseases, where inhibition of TNF has led to significant clinical improvement. However, TNF-activated pathways and mechanisms involved in bone remodeling remain unclear. So far, TNF-α was known as an inhibitor of osteoblast differentiation and an activator of osteoclastogenesis.

Time to internal fixation of femoral neck fractures in patients under sixty years--does this matter in the development of osteonecrosis of femoral head?

Purpose: Osteonecrosis of femoral head remains a major complication of femoral neck fractures. It has been postulated that early internal fixation drastically reduces the incidence of osteonecrosis of the femoral head. However, there is a paucity of literature looking at the effect of time delay to internal fixation on the development of this late complication.

The lipid alterations in the stratum corneum of dogs with atopic dermatitis are alleviated by topical application of a sphingolipid-containing emulsion.

Background: Atopic dermatitis (AD) results from an altered skin barrier associated with defects in the lipid composition of the skin. Dogs with AD present similar clinical symptoms to humans, and may be a useful model for investigations into AD.

Aim: To analyse the changes occurring in the lipids of the stratum corneum (SC) of dogs with AE after 3 weeks of topical treatment with an emulsion containing ceramides, free fatty acids (FFAs) and cholesterol (skin lipid complex; SLC).

Bone marrow-derived and synovium-derived mesenchymal cells promote Th17 cell expansion and activation through caspase 1 activation: contribution to the chronicity of rheumatoid arthritis.

Objective: Th17 cells have been implicated in rheumatoid arthritis (RA). We hypothesized that the interaction of T cells with bone marrow-derived mesenchymal stem cells (BM-MSCs) or with fibroblast- like synoviocytes (FLS) might, with the help of T cell-secreted inflammatory cytokines (i.e.