Patterns of progression on first line osimertinib in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC): A Swiss cohort study.

Aim: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved for patients with EGFR mutated non-small cell lung cancer as first-line treatment. However, treatment resistance inevitably emerges and may present as oligo-progressive disease (OPD) or systemic progressive disease (SPD). The incidence of OPD on first-line osimertinib is unknown.

A multicenter phase II trial of anti-EGFR-immunoliposomes loaded with doxorubicin in patients with advanced triple negative breast cancer.

Advanced triple negative breast cancer (TNBC) is an aggressive, but initially chemo-sensitive disease. The prognosis is poor and more than three quarters of patients experience progression 12 months after the initiation of conventional first-line chemotherapy. Approximately two thirds of TNBC express epidermal growth factor receptor 1 (EGFR).

Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study.

CAPTURE (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively.

Cancer, COVID-19, and Antiviral Immunity: The CAPTURE Study.

The SARS-CoV-2 pandemic has posed a significant challenge for risk evaluation and mitigation among cancer patients. Susceptibility to and severity of COVID-19 in cancer patients has not been studied in a prospective and broadly applicable manner. CAPTURE is a pan-cancer, longitudinal immune profiling study designed to address this knowledge gap.

Oligoprogression After Checkpoint Inhibition in Metastatic Melanoma Treated With Locoregional Therapy: A Single-center Retrospective Analysis.

Checkpoint inhibitors (CPIs) have demonstrated a heterogenous spectrum of response and disease progression that may not be fully captured by conventional response criteria, such as a limited degree of progression, known as oligoprogression, which could benefit from local treatment. We retrospectively analyzed data from all patients diagnosed with metastatic melanoma, who received CPI between January 2006 and March 2018 at Royal Marsden. We enrolled 36 patients who experienced progression in a maximum of 3 metastatic sites, after achieving disease control from therapy with CPI, and were radically treated with the locoregional approach.

Metastatic melanoma: therapeutic agents in preclinical and early clinical development.

: Advanced melanoma historically had a very poor outcome but targeted therapies and immune checkpoint inhibitors (IC) have changed the course of the disease and made durable responses possible. However, most patients will develop progressive disease, so further strategies to overcome treatment resistance are needed. : Current treatment strategies and landmark trials are discussed.

Avelumab and axitinib in the treatment of renal cell carcinoma: safety and efficacy.

: The incidence of advanced renal cell carcinoma (RCC) is increasing. Over the last 10 years targeted therapies have led to improved efficacy outcomes for renal carcinoma, including longer survival. However, the majority of patients develop disease progression within a year of initiation of first-line therapy.

MiRNAs Are Involved in Tall Cell Morphology in Papillary Thyroid Carcinoma.

Unlabelled: Five percent of papillary thyroid carcinomas (PTC) show an adverse clinical outcome (ACO). The tall cell variant of papillary thyroid carcinomas (TCV) is a good predictor of an ACO, however, the identification of tall-cells is subjective. Micro RNAs are short non-coding ribonucleic acids (miRNA).

Endovascular Cooling Catheter for Selective Brain Hypothermia: An Animal Feasibility Study of Cooling Performance.

Background And Purpose: Therapeutic hypothermia represents a promising neuroprotective treatment in acute ischemic stroke. Selective cerebral hypothermia applied early, prior to and during endovascular mechanical recanalization therapy, may be beneficial in the critical phase of reperfusion. We aimed to assess the feasibility of a new intracarotid cooling catheter in an animal model.

Interlaboratory variability of MIB1 staining in well-differentiated pancreatic neuroendocrine tumors.

Neuroendocrine tumors (NET) are routinely graded and staged to judge prognosis. Proliferation index using MIB1 staining has been introduced to assess grading. There are vivid discussions on cutoff definitions, automated counting, and interobserver variability.

Diagnostic and prognostic implications of the PAX8-PPARγ translocation in thyroid carcinomas-a TMA-based study of 226 cases.

Aims: Follicular thyroid carcinoma (FTC) has been a diagnostic challenge for decades. The PAX8-PPARγ rearrangement has been detected in FTC and classic papillary thyroid carcinomas (PTCs). The aims of this study were to assess the presence of PAX8-PPARγ by using tissue microarrays in a large cohort of different thyroid neoplasms, and to assess its diagnostic and prognostic implications.

Where would you turn for help? Older adults' awareness of community support services.

Previous findings on older adults' awareness of community support services (CSSs) have been inconsistent and marred by acquiescence or over-claiming bias. To address this issue, this study used a series of 12 vignettes to describe common situations faced by older adults for which CSSs might be appropriate. In telephone interviews, 1,152 adults aged 50 years and over were read a series of vignettes and asked if they were able to identify a community organization or agency that they may turn to in that situation.

The gender wealth gap:structural and material constraints and implications for later life.

Wealth is an important measure of economic well-being, because while income captures the current state of inequality, wealth has the potential for examining accumulated and historically structured inequality. This presentation documents the extent of gender inequality in wealth for Canadian women and men aged 45 and older. The analysis uses data from the 1999 Canadian Survey of Financial Security, a large nationally representative survey of household wealth in Canada.

Retaining nurses in their employing hospitals and in the profession: effects of job preference, unpaid overtime, importance of earnings and stress.

The purpose of this paper is to examine the effects of job preference, unpaid overtime, importance of earnings, and stress in retaining nurses in their employing hospitals and in the profession. Data come from our survey of 1396 nurses employed in three teaching hospitals in Southern Ontario, Canada. Data are analyzed first for all nurses, then separately for full-time, part-time, and casual nurses.

C3a expressed in the central nervous system protects against LPS-induced shock.

Complement is implicated in the pathogenesis of inflammatory disorders of the central nervous system (CNS), like multiple sclerosis, Alzheimer's disease, and trauma. The anaphylatoxins C3a and C5a are thought to be the major contributors to complement-mediated inflammation in the CNS, likely mediating their effects via their ability to attract and activate leukocytes and common capacity to augment inflammation. For example, in experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis, CNS-specific expression of C3a in C3a/GFAP transgenic mice renders them prone to massive cellular infiltration of the CNS and increases their mortality.

Murine complement C4 is not required for experimental autoimmune encephalomyelitis.

In vitro studies have demonstrated that myelin and myelin-derived proteins activate both the classical and alternative complement pathways. More recently, studies have shown that mice deficient in factor B, a protein required for activation of the alternative pathway, have attenuated experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. The relative contribution of the classical pathway to the pathogenesis of EAE has remained unexplored.

Deletion of the complement anaphylatoxin C3a receptor attenuates, whereas ectopic expression of C3a in the brain exacerbates, experimental autoimmune encephalomyelitis.

The C3aR is expressed throughout the CNS and is increased in expression on glial cells during CNS inflammation. However, the role that C3a and the C3aR play in chronic inflammation, such as in the demyelinating disease experimental autoimmune encephalomyelitis (EAE), remains unclear. We show in this study that deletion of the C3aR is protective in myelin oligodendrocyte glycoprotein-induced EAE in C57BL/6 mice.

Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A.

Plasma membrane GABA transporters participate in neural signaling through re-uptake of neurotransmitter. The domains of the transporter that mediate GABA translocation and regulate transport are not well understood. In the present experiments, the N-terminal cytoplasmic domain of the GABA transporter GAT1 regulated substrate transport rates.