Estimating the cost for obstetric fistula repair in hospitals of Mozambique: a low-income country.

Background: Obstetric fistula is incident and prevalent in low-income countries. Globally, about 100,000 women develop fistula annually. In Mozambique, more than 2,000 fistulas are reported annually.

Patterns of healthcare use among children with immigrant and non-immigrant backgrounds in 2019 and 2020: evidence from the CRIAS cohort study in the metropolitan area of Lisbon, Portugal.

Background: International migrant families may face various barriers in the access and use of health services. Evidence on immigrant children's health care or prevention facilities' utilisation patterns is scarce in Portugal. Therefore, the objectives of this study were to compare health services use between immigrant and non-immigrant children in the Metropolitan Area of Lisbon in 2019-2020 with the aim of informing public policies towards equitable access to, and use of health services.

Wild-Type Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer.

Purpose: Panitumumab, a fully human antibody against the epidermal growth factor receptor (EGFR), has activity in a subset of patients with metastatic colorectal cancer (mCRC). Although activating mutations in KRAS, a small G-protein downstream of EGFR, correlate with poor response to anti-EGFR antibodies in mCRC, their role as a selection marker has not been established in randomized trials.

Patients And Methods: mutations were detected using polymerase chain reaction on DNA from tumor sections collected in a phase III mCRC trial comparing panitumumab monotherapy to best supportive care (BSC).

Detection of chromosomal alteration after infusion of gene-edited allogeneic CAR T cells.

A chromosome 14 inversion was found in a patient who developed bone marrow aplasia following treatment with allogeneic chimeric antigen receptor (CAR) Tcells containing gene edits made with transcription activator-like effector nucleases (TALEN). TALEN editing sites were not involved at either breakpoint. Recombination signal sequences (RSSs) were found suggesting recombination-activating gene (RAG)-mediated activity.

Cohort profile: Health trajectories of Immigrant Children (CRIAS)-a prospective cohort study in the metropolitan area of Lisbon, Portugal.

Purpose: The CRIAS (Health trajectories of Immigrant Children in Amadora) cohort study was created to explore whether children exposed to a migratory process experience different health risks over time, including physical health, cognitive, socioemotional and behavioural challenges and different healthcare utilisation patterns.

Participants: The original CRIAS was set up to include 604 children born in 2015, of whom 50% were immigrants, and their parents. Recruitment of 420 children took place between June 2019 and March 2020 at age 4/5 years, with follow-up carried out at age 5/6 years, at age 6/7 years currently under way.

Are immigrants more vulnerable to the socioeconomic impact of COVID-19? A cross-sectional study in Amadora Municipality, Lisbon metropolitan area.

Introduction: Immigrants carry an extra burden of morbidities and mortalities since the beginning of the coronavirus disease 2019 (COVID-19) pandemic. Pre-existing inequalities among immigrants may threaten their economic wellbeing during the pandemic. This study analyzed the socioeconomic impact of COVID-19 on immigrants and natives living in Amadora, Metropolitan Region of Lisbon and the extent to which preexisting inequalities had been exacerbated during the pandemic.

The first sequenced Sphaerotilus natans bacteriophage- characterization and potential to control its filamentous bacterium host.

Bacteriophages (phages) are ubiquitous entities present in every conceivable habitat as a result of their bacterial parasitism. Their prevalence and impact in the ecology of bacterial communities and their ability to control pathogens make their characterization essential, particularly of new phages, improving knowledge and potential application. The isolation and characterization of a new lytic phage against Sphaerotilus natans strain DSM 6575, named vB_SnaP-R1 (SnaR1), is here described.

Migration as a Determinant in the Development of Children Emotional and Behavior Problems: A Quantitative Study for Lisbon Region, Portugal.

The role of migration as a determinant in child mental health has been demonstrated in a number of studies. However, results are not always consistent, and the research continues to be scarce, especially in Portugal. We examined the association between sociodemographic profiles and the chance for the development of emotional and behavioral difficulties in a group of 420 children, immigrant ( = 217) and born in Portugal to Portuguese born parents ( = 203).

Emergence and dissemination of three mild outbreaks of Neisseria gonorrhoeae with high-level resistance to azithromycin in Barcelona, 2016-18.

Background: Neisseria gonorrhoeae (NG) isolates with high-level azithromycin resistance (HL-AziR) have emerged worldwide in recent decades, threatening the sustainability of current dual-antimicrobial therapy.

Objectives: This study aimed to characterize the first 16 NG isolates with HL-AziR in Barcelona between 2016 and 2018.

Methods: WGS was used to identify the mechanisms of antimicrobial resistance, to establish the MLST ST, NG multiantigen sequence typing (NG-MAST) ST and NG sequence typing for antimicrobial resistance (NG-STAR) ST and to identify the clonal relatedness of the isolates with other closely related NG previously described in other countries based on a whole-genome SNP analysis approach.

: A patent dataset report for research and development (R&D) analysis.

This work shows a patent database for that provides an overview of the patenting activity and trends in focused antiviral therapy with the use of triazole based compounds, glycoprotein, and protease inhibitors as possible treatment. The patent data was obtained from Orbit Intelligence Software using a patent family structure to get a big database that could be used for built patent landscape report (PLR), market analysis, technical and competitive intelligence, and monitoring and survey of a new ideas for the treatment of coronavirus diseases. The raw data is reported in four databases, which were classified according to different items: legal status (alive, dead), 1 application year (after 2015, 2011-2015, 2006-2010, 2001-2005), and Top 5 International Patents Classifications (IPC).

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.

Long-term safety and activity of NY-ESO-1 SPEAR T cells after autologous stem cell transplant for myeloma.

This study in patients with relapsed, refractory, or high-risk multiple myeloma (MM) evaluated the safety and activity of autologous T cells engineered to express an affinity-enhanced T-cell receptor (TCR) that recognizes a peptide shared by cancer antigens New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and L-antigen family member 1 (LAGE-1) and presented by HLA-A*02:01. T cells collected from 25 HLA-A*02:01-positive patients with MM expressing NY-ESO-1 and/or LAGE-1 were activated, transduced with self-inactivating lentiviral vector encoding the NY-ESO-1TCR, and expanded in culture. After myeloablation and autologous stem cell transplant (ASCT), all 25 patients received an infusion of up to 1 × 10 NY-ESO-1 specific peptide enhanced affinity receptor (SPEAR) T cells.

Antitumor Activity Associated with Prolonged Persistence of Adoptively Transferred NY-ESO-1 T Cells in Synovial Sarcoma.

We evaluated the safety and activity of autologous T cells expressing NY-ESO-1, an affinity-enhanced T-cell receptor (TCR) recognizing an HLA-A2-restricted NY-ESO-1/LAGE1a-derived peptide, in patients with metastatic synovial sarcoma (NY-ESO-1T cells). Confirmed antitumor responses occurred in 50% of patients (6/12) and were characterized by tumor shrinkage over several months. Circulating NY-ESO-1T cells were present postinfusion in all patients and persisted for at least 6 months in all responders.

Fludarabine and neurotoxicity in engineered T-cell therapy.

Adoptive T-cell therapy, incorporating engineered T cell receptors (TCRs) or chimeric antigen receptors (CARs), target tumor antigens with high affinity and specificity. To increase the potency of adoptively transferred T cells, patients are conditioned with lymphodepleting chemotherapy regimens prior to adoptive T-cell transfer (ACT), and data suggest that fludarabine is an important component of an effective regimen. In a recent clinical trial using CAR-T cells engineered to target the CD19 B-cell antigen to treat acute lymphoblastic leukemia, JCAR-015 (NCT02535364), two patient deaths due to cerebral edema led to trial suspension.

Tiered application of the neutral red release and EpiOcular™ assays for evaluating the eye irritation potential of agrochemical formulations.

Agrochemical formulations have been underrepresented in validation efforts for implementing alternative eye irritation approaches but represent a significant opportunity to reduce animal testing. This study assesses the utility of the neutral red release assay (NRR) and EpiOcular™ assay (EO) for predicting the eye irritation potential of 64 agrochemical formulations relative to Draize data. In the NRR, formulations with an NRR50 value ≤ 50 mg/mL were categorized as UN GHS Cat 1 and those >250 mg/mL were classified as UN GHS Non Classified (NC).

Application of the KeratinoSens™ assay for assessing the skin sensitization potential of agrochemical active ingredients and formulations.

Assessment of skin sensitization potential is an important component of the safety evaluation process for agrochemical products. Recently, non-animal approaches including the KeratinoSens™ assay have been developed for predicting skin sensitization potential. Assessing the utility of the KeratinoSens™ assay for use with multi-component mixtures such as agrochemical formulations has not been previously evaluated and is a significant need.

Relationships between pazopanib exposure and clinical safety and efficacy in patients with advanced renal cell carcinoma.

Background: Pazopanib, an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR)/c-Kit, is approved in locally advanced/metastatic renal cell carcinoma (RCC).

Methods: Data from trials in advanced solid tumours and advanced/metastatic RCC were used to explore the relationships between plasma pazopanib concentrations and biomarker changes, safety, and efficacy. Initially, the relationships between pharmacokinetic parameters and increased blood pressure were investigated, followed by analysis of steady-state trough concentration (Cτ) and sVEGFR2, safety, progression-free survival (PFS), response rate, and tumour shrinkage.

Prognostic or predictive plasma cytokines and angiogenic factors for patients treated with pazopanib for metastatic renal-cell cancer: a retrospective analysis of phase 2 and phase 3 trials.

Background: Several targeted drugs are approved for treatment of patients with metastatic renal-cell cancer, but no validated biomarkers are available for prediction of clinical outcome. We aimed to assess the prognostic and predictive associations of pretreatment plasma concentrations of cytokine and angiogenic factors (CAFs) with data from a phase 2 and a phase 3 trial of pazopanib treatment.

Methods: We used a three-step approach for screening, confirmation, and validation of prospective CAF biomarkers.

Transarterial chemoembolization plus or minus intravenous bevacizumab in the treatment of hepatocellular cancer: a pilot study.

Background: Stimulation of vascular endothelial growth factor (VEGF) has been observed following transarterial chemoembolization (TACE) in hepatocellular cancer (HCC) and may contribute to tumor regrowth. This pilot study examined whether intravenous (IV) bevacizumab, a monoclonal antibody against VEGF, could inhibit neovessel formation after TACE.

Methods: 30 subjects with HCC undergoing TACE at a single academic institution were randomized with a computer-generated allocation in a one to one ratio to either bevacizumab at a dose of 10 mg/kg IV every 14 days beginning 1 week prior to TACE (TACE-BEV arm) or observation (TACE-O arm).

Predictive genomic biomarkers.

Advances in the biological characterization of tumors has led to the design and development of anticancer agents targeting specific molecular alterations. The majority of these agents are designed to silence phosphorylation signals that are required for the development and maintenance of the cancer phenotype in specific tumor types. Prospective identification of cancer subsets containing particular target alterations is a requirement for these development programs, which in theory, should include smaller trials and result in larger therapeutic benefits.

Triple-drug transcatheter arterial chemoembolization in unresectable hepatocellular carcinoma: assessment of survival in 124 consecutive patients.

Objective: The objective of our study was to describe survival outcome in 124 patients with unresectable hepatocellular carcinoma treated with triple-drug transcatheter arterial chemoembolization (TACE) using doxorubicin, cisplatin, and mitomycin C using a standardized regimen.

Materials And Methods: One hundred twenty-four patients underwent TACE using a standardized triple-drug regimen. Embolization was performed using subselective coaxial embolization technique.

An open-label clinical trial evaluating safety and pharmacokinetics of two dosing schedules of panitumumab in patients with solid tumors.

Purpose: This study evaluated safety, pharmacokinetics, and efficacy of 2 dose schedules and 2 infusion times of panitumumab in patients with advanced solid malignancies.

Patients And Methods: This phase I multicenter, open-label study sequentially enrolled patients with advanced solid tumors refractory to standard therapy, or for which no standard therapy exists, to receive panitumumab 6 mg/kg every 2 weeks or 9 mg/kg every 3 weeks. Patients receiving panitumumab every 2 weeks received either all infusions over 60 minutes or a 60-minute infusion for the first dose followed by 30-minute infusions if the first infusion was well tolerated.

Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy.

Background: The authors explored the association of skin toxicity (ST) severity as measured by patient-reported ST and Common Terminology Criteria for Adverse Events (CTCAE) grading with efficacy of panitumumab, a fully human antiepidermal growth factor receptor antibody, from a phase 3 metastatic colorectal cancer (CRC) trial.

Methods: Patients were randomized to panitumumab plus best supportive care (BSC) vs BSC alone. ST by modified National Cancer Institute CTCAE v3.

A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer.

Purpose: Panitumumab, a fully human antibody targeting the epidermal growth factor receptor, is active in patients with metastatic colorectal cancer (mCRC). This trial evaluated panitumumab added to bevacizumab and chemotherapy (oxaliplatin- and irinotecan-based) as first-line treatment for mCRC.

Patients And Methods: Patients were randomly assigned within each chemotherapy cohort to bevacizumab and chemotherapy with or without panitumumab 6 mg/kg every 2 weeks.

Association of K-ras mutational status and clinical outcomes in patients with metastatic colorectal cancer receiving panitumumab alone.

Background: Identifying predictive biomarkers is important to optimally treat patients. This analysis evaluated the association of K-ras, BRAF, and PIK3CA gene mutations with tumor resistance to panitumumab alone.

Patients And Methods: From 3 phase II panitumumab metastatic colorectal cancer (mCRC) studies, 62 of 533 patient samples were available.