Do proton pump inhibitors affect the effectiveness of cyclin-dependent kinase 4/6 inhibitors in advanced HR positive, HER2 negative breast cancer? A meta-analysis

Background:The CDK 4/6 inhibitors, including palbociclib and ribociclib, are the standard first-line treatment for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer. Proton pump inhibitors are one of the most globally prescribed types of medications as part of the treatment for gastroesophageal reflux and heartburn complaints. Medication interactions have been demonstrated, leading to a decrease in the effectiveness of chemotherapy drugs such as capecitabine and pazopanib. However, their role and interaction with targeted therapies such as CDK inhibitors are still poorly understood.Methods:We searched PubMed, Embase and Web of Science databases for studies that investigated the use of PPI with CDK 4/6 inhibitors versus CDK4/6 alone for advanced or metastatic breast cancer. We systematically searched for the currently available CDK inhibitors: palbociclib, ribociclib and abemaciclib. We computed hazard ratios (HRs), with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I2 statistics. R, version 4.2.3, was used for statistical analyses.Results:A total of 2,737 patients with advanced breast cancer in 9 studies were included, with six studies described the status menopausal as 217 (7.9%) pre-menopause and 1851 (67.6%) post-menopause, for endocrine sensitivity only five studies described1489 (54.4%) patients were endocrine-sensitive and 498 (182%) endocrine-resistent, 910 (33.2%) patients used PPIs. The overall Progression-Free Survival was in favor of the PPI non-users (HR 2.0901; 95% CI 1.410–2.9498; p < 0.001). As well as the subgroup taking palbociclib, revealing statistical relevance for the PPI non-users (HR 2.2539; 95% CI 1.3213–3.8446; p = 0.003) and ribociclib subgroup with a slight decrease in hazard ratio (HR 1.74 95% CI 1.02–2.97; p = 0.04; I2 = 40%). In the multivariate analysis, there was no statistical signifance with ECOG (HR 0.9081; 95% CI 0.4978–16566; p 0.753) and Age (HR 1.2772; 95% CI 0.8790–1.8559; p = 0.199). Either, the univariate analysis did not show statistical significance.Conclusion:Women with HR+ and HER2-advanced metastatic breast undergoing treatment with targeted therapies, specifically CDK 4/6 inhibitors, should be monitored for the use of proton pump inhibitors. Therefore, the use of PPIs should be discussed, weighing the advantages and disadvantages for specific cases. It should be individualized based on the necessity in clinical practice for these cases.Systematic Review Registration:identifier CRD4202348475

Efficacy and safety of Zolbetuximab plus chemotherapy for advanced CLDN18.2-positive gastric or gastro-oesophageal adenocarcinoma: a meta-analysis of randomized clinical trials

Abstract Background The benefit of adding Zolbetuximab to the treatment in patients with Claudin-18 isoform 2 (CLDN18.2)-positive, human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GC/GEJ) is not yet fully elucidated. Methods We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) that investigated Zolbetuximab plus chemotherapy versus chemotherapy alone for GC or GEJ adenocarcinoma. We computed hazard-ratios (HRs) or odds-ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Results Three studies and 1,233 patients were included. Comparing with Zolbetuximab plus chemotherapy versus chemotherapy alone, progression-free survival (PFS) rate (HR 0.64; 95% CI 0.49–0.84; p < 0.01) and overall survival (OS) rate (HR 0.72; 95% CI 0.62–0.83; p < 0.01) were significant in favor of the Zolbetuximab group. Regarding effectiveness, the Objective Response Rate (ORR) was (OR 1.15; 95% CI 0.87–1.53; p = 0.34). Conclusions In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of Zolbetuximab alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with advanced CLDN18.2-positive GC/GEJ cancer

The incidence risk of gynecological cancer by antipsychotic use: a meta-analysis of 50,402 patients

Abstract Background Female gynecological cancers represent a serious public health problem, with 1,398,601 new diagnoses and 671,875 deaths per year worldwide. Antipsychotics are often used in psychiatric disorders, including schizophrenia, bipolar disorder, and major depression. It is estimated that the prescription of these drugs is linked to 1,800 deaths a year in the United States, but their association with cancer remains controversial. Methods We searched PubMed, Scopus, and Web of Science databases for studies reporting the correlation in the incidence risk of gynecological cancer by antipsychotic use. We used DerSimonian and Laird random-effect models to compute logit transformed odds ratio (OR) for the primary binary endpoint with 95% confidence interval (CI). Heterogeneity was assessed through effect size width along with I-squared and Tau-squared statistics. Review Manager 5.4.1. was used for statistical analyses. A p-value of < 0.05 denoted statistically significant. Results 50,402 patients were included, of whom 778 (1,54%) took antipsychotic medication for at least 1 year. 1,086 (2,15%) with ovarian cancer and 49,316 (97,85%) with endometrial cancer. Antipsychotic use (OR 1.50; 1.06 to 2.13 95% CI; p-value 0.02), hypertension (OR 1.50; 95% CI 1.06 to 2.13; p-value < 0.01), nulliparity (OR 1.98; 95% CI 1.53 to 2.57; p-value < 0.01) and multiparity (OR 0.53; 95% CI 0.41 to 0.69; p-value < 0.01) showed significantly different distributions between groups of cancer and cancer-free patients. The primary endpoint of incidence risk of gynecological cancer by antipsychotic therapy showed a statistically significant difference (OR 1.67; 95% CI 1.02 to 2.73; p-value < 0.05) against the use of antipsychotic drugs. Conclusions Our meta-analysis showed that the use of antipsychotic drugs increases the risk of gynecological cancers, particularly endometrial cancer. This result should be weighed against the potential effects of treatment for a balanced prescribing decision

Fezolinetant for the treatment of vasomotor symptoms associated with menopause: a meta-analysis

This systematic review and meta-analysis investigated the efficacy and safety of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause. PubMed, Cochrane Library, Embase and Web of Science were searched for randomized controlled trials (RCTs) published from inception to June 2023, comparing fezolinetant to placebo in postmenopausal women suffering from moderate-to-severe VMS. The mean difference and risk ratio were calculated for continuous and binary outcomes, respectively. R software was used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. We performed subgroup analysis based on different dosing regimens. Five RCTs comprising 3302 patients were included. Compared with placebo, at 12-week follow-up, fezolinetant significantly reduced the daily frequency of moderate-to-severe VMS (weighted mean difference [WMD] − 2.36; 95% confidence interval [CI] − 2.92, −1.81) and daily severity of moderate-to-severe VMS (WMD −0.22; 95% CI −0.31, −0.13). Also, fezolinetant significantly improved the quality of life (WMD −0.42; 95% CI −0.58, −0.26) and sleep disturbance (WMD −1.10; 95% CI −1.96, −0.24). There were no significant differences between groups in adverse events. These findings support the efficacy and safety of fezolinetant for the treatment of VMS related to menopause.</p

Número Completo, vol 40, n. 2, Jul/JDez 2014

Introduction: This study aimed to identify the epidemiological profile of drowning victims in the State of Pará from 2010 to 2019. Objective: To trace the epidemiological profile of drowning deaths in the State of Pará from 2010 to 2019. Methods: Analysis of data obtained through the online platform of the Informatics Department of the Unified Health System (DataSus). Results: In the period, 3,144 deaths were registered due to accidental drowning and submersion, of which 82.6% were male and self-declared brown (82.54%). The age group with the highest number of cases was 20 to 29 years old, followed by the age group 1 to 4 years old. The municipalities that registered the highest number of deaths were Belém, Marabá and Santarém. Conclusion: There is a need for further discussions on the subject, as data on the characterization of the epidemiological profile of drowning victims will allow specific preventive actions for certain age groups in locations and populations where these numbers are more expressive.Introducción: Este estudio tuvo como objetivo identificar el perfil epidemiológico de las víctimas de ahogamiento en el Estado de Pará de 2010 a 2019. Objetivo: Trazar el perfil epidemiológico de las muertes por ahogamiento en el Estado de Pará de 2010 a 2019. Métodos: Análisis de datos obtenidos mediante la plataforma en línea del Departamento de Informática del Sistema Único de Salud (DataSus). Resultados: En el período se registraron 3.144 muertes por ahogamiento accidental e inmersión, de las cuales el 82,6% fueron varones y se declararon pardos (82,54%). El grupo de edad con mayor número de casos fue el de 20 a 29 años, seguido del grupo de 1 a 4 años. Los municipios que registraron el mayor número de muertes fueron Belém, Marabá y Santarém. Conclusión: Es necesario profundizar en el debate sobre el tema, ya que los datos sobre la caracterización del perfil epidemiológico de las víctimas de ahogamiento permitirán acciones preventivas específicas para determinados grupos de edad en localizaciones y poblaciones donde estos números son más expresivos.Introdução: Este trabalho teve o intuito de identificar o perfil epidemiológico das vítimas de afogamento do Estado do Pará entre o ano de 2010 a 2019. Objetivo: Traçar o perfil epidemiológico dos óbitos por afogamento no estado do Pará no período de 2010 a 2019. Métodos: Análise dos dados obtidos através da plataforma online do Departamento de Informática do Sistema Único de Saúde (DataSus). Resultados: No período, foram registrados 3.144 óbitos por afogamento e submersão acidentais, desses, 82,6% eram do sexo masculino e autodeclarados pardos (82,54%). A faixa etária com maior número de casos foi de 20 a 29 anos seguida pela faixa etária de 1 a 4 anos. Os municípios que registraram maior número de mortes foram Belém, Marabá e Santarém. Conclusão: Há necessidade de maiores discussões sobre o assunto, pois dados sobre a caracterização do perfil epidemiológico das vítimas de afogamento permitirá ações preventivas específicas para determinadas faixas etárias em localidades e populações onde estes números são mais expressivos

Effect of American genomic ancestry on severe toxicities in children with acute lymphoblastic leukemia in the Amazon region

Abstract Background Acute Lymphoblastic Leukemia (ALL) is a neoplasm of the hematopoietic system characterized by a clonal expansion of abnormal lymphocyte precursor cells. ALL is the most common form of cancer in children, but despite advances in treatment, it can still be fatal. Ethnic differences influence survival rates, and genomic ancestry plays an important role, especially in mixed-race populations such as Latin America. This study aims to analyze the influence of genomic ancestry on toxicity in children with ALL in the Amazon region. Methods The study included 171 patients (protocol number 119,649/2012—Ethics Committee) with ALL treated at a pediatric treatment center in Belém do Pará, in the Brazilian Amazon. The patients were submitted to the BFM protocol of induction therapy for ALL. Toxicity was assessed based on laboratory tests and adverse events, classified according to the CTC-NCI guide. Genomic ancestry was determined using autosomal informative markers. Results The majority of children (94.74%) developed some type of toxicity during treatment, 87.04% of which were severe. Infectious toxicity was the most common, present in 84.8% of cases, 77.24% of which were severe. Amerindian ancestry showed an association with the risk of severe general toxicity and severe infectious toxicity, with a contribution of 35.0% demonstrating a significant increase in risk. In addition, post-induction refractoriness and relapse were also associated with an increased risk of death. Conclusion This study highlights the influence of Amerindian genomic ancestry on response to therapy and toxicity in children with ALL in the Amazon region. Understanding these associations can contribute to personalizing treatment and improving clinical outcomes

Molecular Profile of Variants Potentially Associated with Severe Forms of COVID-19 in Amazonian Indigenous Populations

Coronavirus disease 2019 (COVID-19) is an infection caused by SARS-CoV-2. Genome-wide association studies (GWASs) have suggested a strong association of genetic factors with the severity of the disease. However, many of these studies have been completed in European populations, and little is known about the genetic variability of indigenous peoples’ underlying infection by SARS-CoV-2. The objective of the study is to investigate genetic variants present in the genes AQP3, ARHGAP27, ELF5L, IFNAR2, LIMD1, OAS1 and UPK1A, selected due to their association with the severity of COVID-19, in a sample of indigenous people from the Brazilian Amazon in order to describe potential new and already studied variants. We performed the complete sequencing of the exome of 64 healthy indigenous people from the Brazilian Amazon. The allele frequency data of the population were compared with data from other continental populations. A total of 66 variants present in the seven genes studied were identified, including a variant with a high impact on the ARHGAP27 gene (rs201721078) and three new variants located in the Amazon Indigenous populations (INDG) present in the AQP3, IFNAR2 and LIMD1 genes, with low, moderate and modifier impact, respectively

NEOTROPICAL FRESHWATER FISHES: A dataset of occurrence and abundance of freshwater fishes in the Neotropics

The Neotropical region hosts 4225 freshwater fish species, ranking first among the world's most diverse regions for freshwater fishes. Our NEOTROPICAL FRESHWATER FISHES data set is the first to produce a large-scale Neotropical freshwater fish inventory, covering the entire Neotropical region from Mexico and the Caribbean in the north to the southern limits in Argentina, Paraguay, Chile, and Uruguay. We compiled 185,787 distribution records, with unique georeferenced coordinates, for the 4225 species, represented by occurrence and abundance data. The number of species for the most numerous orders are as follows: Characiformes (1289), Siluriformes (1384), Cichliformes (354), Cyprinodontiformes (245), and Gymnotiformes (135). The most recorded species was the characid Astyanax fasciatus (4696 records). We registered 116,802 distribution records for native species, compared to 1802 distribution records for nonnative species. The main aim of the NEOTROPICAL FRESHWATER FISHES data set was to make these occurrence and abundance data accessible for international researchers to develop ecological and macroecological studies, from local to regional scales, with focal fish species, families, or orders. We anticipate that the NEOTROPICAL FRESHWATER FISHES data set will be valuable for studies on a wide range of ecological processes, such as trophic cascades, fishery pressure, the effects of habitat loss and fragmentation, and the impacts of species invasion and climate change. There are no copyright restrictions on the data, and please cite this data paper when using the data in publications

Neotropical freshwater fisheries : A dataset of occurrence and abundance of freshwater fishes in the Neotropics

The Neotropical region hosts 4225 freshwater fish species, ranking first among the world's most diverse regions for freshwater fishes. Our NEOTROPICAL FRESHWATER FISHES data set is the first to produce a large-scale Neotropical freshwater fish inventory, covering the entire Neotropical region from Mexico and the Caribbean in the north to the southern limits in Argentina, Paraguay, Chile, and Uruguay. We compiled 185,787 distribution records, with unique georeferenced coordinates, for the 4225 species, represented by occurrence and abundance data. The number of species for the most numerous orders are as follows: Characiformes (1289), Siluriformes (1384), Cichliformes (354), Cyprinodontiformes (245), and Gymnotiformes (135). The most recorded species was the characid Astyanax fasciatus (4696 records). We registered 116,802 distribution records for native species, compared to 1802 distribution records for nonnative species. The main aim of the NEOTROPICAL FRESHWATER FISHES data set was to make these occurrence and abundance data accessible for international researchers to develop ecological and macroecological studies, from local to regional scales, with focal fish species, families, or orders. We anticipate that the NEOTROPICAL FRESHWATER FISHES data set will be valuable for studies on a wide range of ecological processes, such as trophic cascades, fishery pressure, the effects of habitat loss and fragmentation, and the impacts of species invasion and climate change. There are no copyright restrictions on the data, and please cite this data paper when using the data in publications