Health system collapse 45 days after the detection of COVID-19 in Ceará, Northeast Brazil: a preliminary analysis.

Introduction: COVID-19 emerged in late 2019 and quickly became a serious public health problem worldwide. This study aim to describe the epidemiological course of cases and deaths due to COVID-19 and their impact on hospital bed occupancy rates in the first 45 days of the epidemic in the state of Ceará, Northeastern Brazil.

Methods: The study used an ecological design with data gathered from multiple government and health care sources.

Toxicological considerations in the treatment of axial spondylo-arthritis.

Introduction: The first-line treatment of axial spondyloarthritis (SpA) is with non-steroidal anti-inflammatory drugs (NSAIDs) and is followed by tumor necrosis factor (TNF) inhibitors (the main treatment for patients not responding to NSAIDs) or drugs targetting the IL-23/IL-17 pathway. The efficacy of disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate and sulfasalazine (SSZ) has not been demonstrated, although SSZ can be considered in patients with concomitant peripheral arthritis.

Areas Covered: This review describes the beneficial and toxicological effects of the drugs used to treat axial SpA.

Relationships between informal caregiving, health and work in the Health and Employment After Fifty study, England.

Background: To investigate the prevalence of caregiving and its relationship with work, health and socio-economic circumstances in the Health and Employment After Fifty (HEAF) study.

Methods: The HEAF study comprises 8134 men and women aged 50-64 years recruited from 24 general practices. Socio-demographic, lifestyle and health characteristics and hours per week giving personal care were elicited by postal questionnaire.

Patient Experiences with Avelumab in Treatment-Naïve Metastatic Merkel Cell Carcinoma: Longitudinal Qualitative Interview Findings from JAVELIN Merkel 200, a Registrational Clinical Trial.

Background And Objective: Avelumab is approved for the treatment of metastatic Merkel cell carcinoma, a rare aggressive skin cancer with a poor prognosis. The aim of this qualitative study embedded in a clinical trial was to explore patient experiences while receiving avelumab.

Methods: All treatment-naïve patients with metastatic Merkel cell carcinoma entering part B of the phase II, open-label, international, JAVELIN Merkel 200 trial (NCT02155647) were invited to participate in optional semi-structured phone interviews before avelumab administration (baseline) and at weeks 13 and 25.

PD1/PD-L1 targeting in advanced soft-tissue sarcomas: a pooled analysis of phase II trials.

Immune checkpoint inhibitors, especially the programmed cell death receptor-1/ligand 1 (PD-1/L1) inhibitors, displayed promising efficacy in several solid tumor types and hematological malignancies. Data related to their activity in soft-tissue sarcomas (STS) are scarce.We performed a pooled analysis of clinical trials investigating a PD1 or PD-L1 antagonist in patients with advanced STS.

Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial.

Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with a high risk of metastasis. In 2017, avelumab (anti-programmed death-ligand 1 (PD-L1)) became the first approved treatment for patients with metastatic MCC (mMCC), based on the occurrence of durable responses in a subset of patients. Here, we report long-term efficacy and safety data and exploratory biomarker analyses in patients with mMCC treated with avelumab.

Correlation of Tumor Necrosis Factor-α -308G>A Polymorphism with Susceptibility, Clinical Manifestations, and Severity in Behçet Syndrome: Evidences from an Italian Genetic Case-Control Study.

To investigate the association between a functional drug-response tumor necrosis factor (TNF)α gene polymorphism (at the positions of -308; rs1800629; NG_007462.1:g.4682G>A) and both disease susceptibility and clinical manifestations in a cohort of 130 Italian patients with Behçet syndrome (BS).

Systemic sclerosis Progression INvestiGation (SPRING) Italian registry: demographic and clinico-serological features of the scleroderma spectrum.

Objectives: Systemic sclerosis (SSc) is a severe multiple-organ disease characterised by unpredictable clinical course, inadequate response to treatment, and poor prognosis. National SSc registries may provide large and representative patients cohorts required for descriptive and prognostic studies. Therefore, the Italian Society for Rheumatology promoted the registry SPRING (Systemic sclerosis Progression INvestiGation).

Relative burden of lung and pleural cancers from exposure to asbestos: a cross-sectional analysis of occupational mortality in England and Wales.

Objectives: To explore the extent to which asbestos-exposed jobs vary in the ratio of excess mortality from lung cancer to deaths from pleural cancer.

Design: Using data on underlying cause of death and last full-time occupation for 3 688 916 deaths among men aged 20-74 years in England and Wales during 1979-2010, we calculated proportional mortality ratios (PMRs), standardised for age and social class, with all occupations combined as reference. For each of 22 asbestos-exposed job groups with significantly elevated PMRs for pleural cancer, we calculated excess mortality from lung cancer (observed minus expected deaths) and its ratio to number of deaths from pleural cancer.

Amongst patients taking biologic therapies for axial spondyloarthritis, which factors are associated with work non-participation?

Background: Axial spondyloarthritis (axSpA) frequently presents during working age and therefore impacts work participation. Biologic therapies have demonstrated a positive impact on work-related outcomes in clinical trials but real world data are limited. Therefore, we investigated the prevalence and predictors of work impairment and disability among axSpA patients attending a biologic therapy clinic.

Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: A structured literature review.

We aimed to perform a structured literature review of spinal radiographic progression, as assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), in patients with ankylosing spondylitis (AS) or nonradiographic axial spondyloarthritis (nr-axSpA) treated with biologic therapy. Searches were limited to English language manuscripts published in the 11 years prior to 9 July 2019. Randomized controlled trials, open-label extensions (OLEs) and observational studies reporting mSASSS progression in patients with AS or nr-axSpA treated with biologics were eligible for inclusion.

Assessing vitamin D levels in an anti-DFS70 positive population: New insights emerging.

Anti-dense fine speckled 70 (DFS70) autoantibodies have more often been described in apparently healthy individuals than in patients with systemic autoimmune rheumatic diseases (SARD). The aim of this study was to explore the link between anti-DFS70 autoantibodies and vitamin D (25(OH)D) levels in an Italian adult cohort. Serum samples from 34 (five males and 29 females) anti-DFS70 positive patients (index cases), 34 ANA-negative healthy controls, 34 ANA-positive anti-DFS70 negative SLE patients, both groups age- and gender-matched with the index cases, 23 ANA-positive anti-DFS70 negative healthy blood donors and six female SARD patients showing mixed DFS positive pattern were collected and tested for 25(OH)D levels.

Analysis of the Chemotherapy-Free Interval following Image-Guided Ablation in Sarcoma Patients.

One way to enhance quality of life for patients with metastatic sarcoma is to maximize time off chemotherapy-a chemotherapy-free interval. While image-guided ablation of sarcoma metastases may reduce the need for chemotherapy, it remains unknown how long ablation could extend the chemotherapy-free interval. The purpose of our study was to determine the chemotherapy-free interval in comparison to overall survival and progression-free survival in sarcoma patients who undergo ablation procedures.

Body Mass Index (BMI) and Work Ability in Older Workers: Results from the Health and Employment after Fifty (HEAF) Prospective Cohort Study.

This study explores associations between BMI and prolonged sickness absence; cutting down at work; and health-related job loss (HRJL) over two years of follow-up among workers aged ≥50 years. A cohort of 2299 men and 2425 women (aged 50-64 years) self-reported height and weight at baseline and provided information about work ability at 12 and 24 months for the Health and Employment after Fifty (HEAF) Study. Associations between BMI and work ability were assessed by logistic regression and HRJL by multiple-record Cox's proportional hazards models, with adjustment for other risk factors.

Improvement of Function and Its Determinants in a Group of Axial Spondyloarthritis Patients Treated with TNF Inhibitors: A Real-Life Study.

Introduction: The aim of this work is to investigate the improvement of physical function and its determinants in axial spondyloarthritis (SpA) patients treated with tumor necrosis factor (TNF) inhibitors in a real clinical practice setting.

Methods: An observational study was conducted in patients with axial SpA treated with anti-TNF from 2010 to 2018 with a minimum 6 months of follow-up. All patients fulfilled ASAS or the modified New York criteria.

The Epigenetics of the Endocannabinoid System.

The endocannabinoid system (ES) is a cell-signalling system widely distributed in biological tissues that includes endogenous ligands, receptors, and biosynthetic and hydrolysing machineries. The impairment of the ES has been associated to several pathological conditions like behavioural, neurological, or metabolic disorders and infertility, suggesting that the modulation of this system may be critical for the maintenance of health status and disease treatment. Lifestyle and environmental factors can exert long-term effects on gene expression without any change in the nucleotide sequence of DNA, affecting health maintenance and influencing both disease load and resistance.

Quality indicators for hyperthermia treatment: Italian survey analysis.

Aim: Nowadays, no Quality Indicators (QI) have been proposed for Hyperthermia treatments. Starting from radiotherapy experience, the aim of this work is to adapt radiotherapy indicators to Hyperthermia and to propose a new specific set of QI in Hyperthermia field.

Material And Methods: At first, radiotherapy quality indicators published in literature have been adapted to hyperthermia setting.

Objective Response Rate Among Patients With Locally Advanced or Metastatic Sarcoma Treated With Talimogene Laherparepvec in Combination With Pembrolizumab: A Phase 2 Clinical Trial.

Importance: Patients with advanced sarcoma have limited treatment options. Talimogene laherparepvec (T-VEC) has been shown to increase tumor-specific immune activation via augmenting antigen presentation and T-cell priming.

Objective: To examine whether T-VEC in combination with pembrolizumab is associated with increased tumor-infiltrating lymphocyte infiltration and programmed death-ligand 1 expression and thus with increased antitumor activity in patients with locally advanced or metastatic sarcoma.

Effectiveness of Adalimumab for the Treatment of Psoriatic Arthritis: An Italian Real-Life Retrospective Study.

Few studies have evaluated the effectiveness of adalimumab in the real-life setting in psoriatic arthritis (PsA). To evaluate the 2-year retention rate of adalimumab in PsA patients. Potential baseline parameters influencing persistence on treatment were also evaluated.

Exploiting next-generation sequencing in antibody selections - a simple PCR method to recover binders.

Antibody discovery using display technologies such as phage and/or yeast display has become acornerstone in many research and development projects, including the creation of new drugs for clinical use. Traditionally, after the selection phase, random clones are isolated for binding validation and Sanger sequencing. More recently, next-generation sequencing (NGS) technology has allowed deeper insight into the antibody population after aselection campaign, enabling the identification of many more specific binders.

From structure to function for the characterization of ERAP1 active site in Behçet syndrome. A novel polymorphism associated with known gene variations.

Introduction: ERAP1 has been recently proposed as risk marker of Behçet syndrome (BS). Gene single nucleotide polymorphisms (SNPs) could affect the enzymatic activity and the conserved active site is pivotal for the aminopeptidase function. This study aims to characterize the ERAP1 active site in a cohort of BS patients vs healthy controls (HC) integrating genomics, transcriptomics and bioinformatics approach.

Recombinant peptide derived from the venom the Phoneutria nigriventer spider relieves nociception by nerve deafferentation.

The avulsion of nerve roots of the brachial plexus that is commonly seen in motorcycle accidents is a type of neuropathy due to deafferentation. This type of pain is clinically challenging since therapeutical protocols fail or have severe side effects. Thus, it is proposed to evaluate the antinociceptive activity of the recombinant CTK 01512-2 peptide that is derived from the venom of the Phoneutria nigriventer spider, as a future new therapeutical option.

Systemic and local immunity following adoptive transfer of NY-ESO-1 SPEAR T cells in synovial sarcoma.

Background: Gene-modified autologous T cells expressing NY-ESO-1, an affinity-enhanced T-cell receptor (TCR) reactive against the NY-ESO-1-specific HLA-A*02-restricted peptide SLLMWITQC (NY-ESO-1 SPEAR T-cells; GSK 794), have demonstrated clinical activity in patients with advanced synovial sarcoma (SS). The factors contributing to gene-modified T-cell expansion and the changes within the tumor microenvironment (TME) following T-cell infusion remain unclear. These studies address the immunological mechanisms of response and resistance in patients with SS treated with NY-ESO-1 SPEAR T-cells.