Outcomes of Budesonide as a Treatment Option for Immune Checkpoint Inhibitor-Related Colitis in Patients with Cancer.

BACKGROUND: Current treatment guidelines for moderate to severe colitis (IMC) secondary to immune checkpoint inhibitors (ICI) recommend systemic corticosteroids as the primary therapy in conjunction with biologics, namely infliximab and/or vedolizumab. We aimed to explore the efficacy and safety of oral budesonide in the treatment of IMC. METHODS: We performed a retrospective analysis at MD Anderson Cancer Center of adult cancer patients with a confirmed (based on clinical, radiographic and laboratory assessment) diagnosis of IMC between 1 January 2015 and 31 November 2022, treated with budesonide. Data collection included demographics, oncologic history, IMC-related information and outcomes up to 6 months after the last dose of ICI. RESULTS: Our sample (n = 69) comprised primarily of Caucasian (76.8%) females (55.1%). The majority of patients received combination therapy with anti-PD-1/L1 and anti-CTLA-4 (49.3%), and the most common malignancy treated was melanoma (37.6%). The median grade of diarrhea was 3 and of colitis was 2. Of the 50 patients who underwent endoscopic evaluation, a majority had non-ulcerative inflammation (64%) and active colitis on histology (78%). Budesonide was used as primary treatment at onset of IMC in 56.5% patients, as well as a bridging therapy from systemic corticosteroids in 33.3%. Less than half of the patients (44.9%) required additional therapies such as biologics or fecal microbiota transplant. Additionally, 75.3% of patients achieved full remission of IMC and 24.6% had a recurrence of IMC. ICI was resumed in 31.9% of patients and 17.4% received other forms of cancer therapies. CONCLUSIONS: Budesonide may be an effective strategy to treat and prevent the recurrence of IMC. The remission rates observed in our analysis with budesonide alone are comparable to systemic corticosteroids. Patients that require an extended duration of steroid exposure and those with moderate to severe colitis may benefit from budesonide given its lower risk of infection and complications. Furthermore, we observe that budesonide may serve as a successful bridge from systemic corticosteroids with subsequent biologic treatment. Larger prospective studies are necessary to determine the role of budesonide as well as its safety profile.

Gender differences in the pathway of childhood trauma, impulsivity and adult eating behaviour: a cross-sectional study.

Objective: The current cross-sectional study aimed to examine the association between childhood trauma, impulsivity, binge eating symptoms, and body mass index (BMI) in a sample of males and females. We also aimed to investigate the indirect association of childhood trauma with binge eating through impulsivity while controlling for BMI.Method: Participants were 410 young adults (mean age = 20.9 years, range 18-24; female = 73.9%) who completed online measures of childhood trauma, impulsivity, binge eating symptoms, and self-reported height and weight. Mediation models were tested using multi-group structural equation modelling.Results: Childhood trauma and impulsivity were associated with an increased risk of binge eating symptoms in females but not males, corroborating previous studies. There was a significant difference in the binge eating symptoms index between sexes, but not regarding the index of childhood trauma and impulsivity. Additionally, adverse childhood experiences were associated with impulsivity and the association of childhood trauma with binge eating was mediated by impulsivity in the female sample.Conclusions: Our results suggest sex-dependent patterns and risk factors that may impact binge eating symptoms. The implications of our results suggest that impulsivity might be a vulnerability factor for binge eating, especially for females.

Genetic legacies of mega-landslides: Cycles of isolation and contact across flank collapses in an oceanic island.

Catastrophic flank collapses are recognized as important drivers of insular biodiversity dynamics, through the disruption of species ranges and subsequent allopatric divergence. However, little empirical data supports this conjecture, with their evolutionary consequences remaining poorly understood. Using genome-wide data within a population genomics and phylogenomics framework, we evaluate how mega-landslides have impacted evolutionary and demographic history within a species complex of weevils (Curculionidae) within the Canary Island of Tenerife. We reveal a complex genomic landscape, within which individuals of single ancestry were sampled in areas characterized by long-term geological stability, relative to the timing of flank collapses. In contrast, individuals of admixed ancestry were almost exclusively sampled within the boundaries of flank collapses. Estimated divergence times among ancestral populations aligned with the timings of mega-landslide events. Our results provide first evidence for a cyclical dynamic of range fragmentation and secondary contact across flank collapse landscapes, with support for a model where this dynamic is mediated by Quaternary climate oscillations. The context within which we reveal climate and topography to interact cyclically through time to shape the geographic structure of genetic variation, together with related recent work, highlights the importance of topoclimatic phenomena as an agent of diversification within insular invertebrates.

Association between hospitalizations for sensitive conditions and quality of primary care.

OBJECTIVE: To analyze the association between municipal rates of ambulatory care sensitive conditions (ACSC) hospitalization and the quality of primary health care (PHC), socioeconomic, and demographic variables and those related to local characteristics of the health system from 2010 to 2019. METHOD: Ecological time series study in Brazilian municipalities analyzing the correlation of ACSC hospitalization rates with PHC quality measured by the three cycles of the Primary Care Access and Program for improving primary care access and quality (PMAQ-AB). The study included municipalities whose teams participated in 80% or more of at least two PMAQ-AB cycles. The correlation between standardized ACSC hospitalization rates and PHC quality and other variables was analyzed. Spearman's test was used between the response variable and numerical explanatory variables. Generalized equations estimation was used as a multivariate model associating ACSC hospitalization rates with the other variables over the years. RESULTS: A total of 3,500 municipalities were included in the models. The quality of PHC (PMAQ-AB score) showed an inverse association with the variation in ACSC hospitalization rates. Hospitalization rates fell by -2% per year every ten-point increase in the PMAQ-AB score, adjusted by the remaining variables. A one-unit increase in the beds per 1,000 inhabitants variable had an impact of approximately +6.4% on ACSC hospitalization rates. Regarding population size, larger municipalities had lower ACSC hospitalization rates. Increased PHC coverage and lower socioeconomic inequality were also associated with the reduction in hospitalizations. CONCLUSIONS: The reduction in ACSC hospitalization rates over time was associated with an increase in the quality of PHC. It was also associated with a reduction in the number of hospital beds and municipalities with better socioeconomic indicators.

The Safety of Immunosuppressants Used in the Treatment of Immune-Related Adverse Events due to Immune Checkpoint Inhibitors: a Systematic Review.

Purpose: Immune checkpoint inhibitor (ICI) use can lead to immune-related adverse events (irAEs) that require treatment with immunosuppressive medications in moderate to severe cases. Oncology society guidelines recommend systemic steroids and immunosuppressants such as infliximab and vedolizumab for the treatment of refractory cases. Limited information is available about the safety profile and potential adverse effects of these immunosuppressants. We have investigated the safety profile of multiple immunosuppressants which are used in the treatment of ICI-related irAEs. Methods: We performed a systematic review of studies reporting irAEs, from ICI use, and their medical management with immunosuppressants in adult cancer patients. We searched MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov from inception through September 1, 2022, using the following keywords or their equivalents: ICI, immunosuppressant, and irAE. We extracted observational studies and clinical trials that matched our criteria. A random effects model was used to estimate the overall incidence of infections associated with the treatment of irAEs. Results: Among the 11 studies included in this review (1036 total patients), melanoma (548 patients, 52.9%) was the most common primary cancer, followed by lung cancer (139 patients, 13.4%) and genitourinary cancers (131 patients, 12.6%). PD-1/PD-L1 monotherapy (460 patients, 44.4%) was used most, followed by a combination of PD-1/PD-L1 and CTLA-4 therapy (350 patients, 33.8%) and CTLA-4 monotherapy (226 patients, 22%). A total of 1024 (98.8%) patients had their irAEs treated with systemic steroids with majority having colitis and hepatobiliary irAEs; 335 patients (32.3%) were also treated with infliximab (mainly for colitis). Our review found 22.3% of patients treated for irAEs developed infectious adverse events (95% CI: 15.6%-29.1%, p<0.001). Among the 3 studies reporting the types of infections (41 total patients), bacterial (80.5%), followed by fungal (36.6%), infections were most common. Conclusions: Adverse events from irAE treatment occurred in about one-third of patients that received either steroids or a combination of steroids and other immunosuppressants. Clinicians should be aware of these immunosuppressant-related adverse effects, which can negatively impact cancer treatment and patient outcomes, when treating irAEs and consider shortening treatment duration or using alternative strategies when possible to mitigate these complications, future prospective studies should further investigate the safety of immunosuppressants in treating irAEs.

Transformations in the world of healthcare work: workers and future challenges. / Transformações no mundo do trabalho em saúde: os(as) trabalhadores(as) e desafios futuros.

This article addresses the world of healthcare work, especially in the Brazilian Unified Healthcare System (SUS) in the context of the COVID-19 pandemic in Brazil. This study used data from the following surveys: "Working conditions of health professionals in the context of COVID-19 in Brazil" and "The Invisible health workers: working conditions and mental health in the context of COVID-19 in Brazil". Data analysis proves that the pandemic highlighted existing structural problems within SUS, involving the issue of healthcare workforce (HWF) management, which can be interpreted as another reflection of the socioeconomic inequalities that already exist in the country. This article highlights: the reduced provision of permanent education, the regulation of hybrid care, precariousness, a lack of protection in the work environment, as well as fragile biosecurity leading to tragic rates of illness and death of health workers. Our study concludes by showing the importance of formulating public policies in the scope of education and work management in SUS that ensure the discussion on hybrid care as a new way of acting without losing quality, together with the need to review issues related to permanent education, protection, valuation, and reduction of inequalities pointed out among the professional contingents analyzed in this article.

O artigo versa sobre o mundo do trabalho da saúde, especialmente no SUS no contexto da pandemia no Brasil. O artigo utilizou dados das pesquisas "Condições de trabalho dos profissionais de saúde no contexto da COVID-19 no Brasil" e "Os trabalhadores invisíveis da saúde: condições de trabalho e saúde mental no contexto da COVID-19 no Brasil". A análise dos dados comprova que a pandemia evidenciou problemas estruturais existentes no âmbito do Sistema Único de Saúde, envolvendo a gestão da FTS o que pode ser interpretado como mais um dos reflexos das desigualdades socioeconômicas já existentes no país. Destacam-se: a reduzida oferta de educação permanente, a regulação do cuidado híbrido, precarização, desproteção no ambiente de trabalho, frágil biossegurança levando a trágicas taxas de adoecimento e mortes de trabalhadores da saúde. Conclui mostrando a importância de formulação de políticas públicas no âmbito da gestão da educação e do trabalho no SUS que assegurem a discussão sobre cuidado híbrido como nova forma de atuar sem perder qualidade, a necessidade de se rever questões referentes a: educação permanente, proteção, valorização e redução das desigualdades apontadas entre os contingentes profissionais analisados nesse artigo.

Comorbities and mental health among healthcare workers in Brazil. The impact of the COVID-19 pandemic. / Comorbidades e saúde mental dos trabalhadores da saúde no Brasil. O impacto da pandemia da COVID-19.

This is an original article that addresses the healthcare workforce (HW) in Brazil, as well as comorbidities and mental health changes during the COVID-19 pandemic. This study was conducted by the Oswaldo Cruz Foundation and collected data through an online questionnaires from a total of 36,612 participants, health professionals (HP, with higher education level), and invisible healthcare workers (IHW, with a technical mid-level education). The overall prevalence of comorbidities in Brazil was 26.1% and 23.9%; the highest was arterial hypertension (27.4% and 31.9%), followed by obesity (18.4% and 15.1%), chronic respiratory diseases (15.7% and 12.9%), diabetes mellitus (10.3% and 10.4%), and depression/anxiety (9.1% and 11.7%), in the HW and IHW, respectively. The region with the highest frequency was the southeast, where the largest contingent of workers is located. The HW, affected with a high burden of non-communicable chronic diseases and exposed to SARS-CoV-2, proved to be vulnerable to illness and death. Mental symptoms and intense psychological suffering have been reported. These results allow us to estimate the impacts upon physical and mental health, as well as upon living and working conditions of the HW. The health and life of workers, leading role in facing health challenges of the pandemic, are a high priority in public policies.

Trata-se de um artigo original que aborda a força de trabalho (FT) em saúde no Brasil, suas comorbidades e alterações da saúde mental na pandemia da COVID-19. O estudo conduzido pela Fundação Oswaldo Cruz coletou dados por meio de questionário on-line com um total de 36.612 participantes: profissionais de saúde (PS, formação de nível superior), e trabalhadores invisíveis (TI, nível técnico). A prevalência de comorbidades no Brasil foi de 26,1% e 23,9%, a maior foi hipertensão arterial (27,4% e 31,9%), seguida da obesidade (18,4% e 15,1%), doenças crônicas respiratórias (15,7% e 12,9%), diabetes mellitus (10,3% e 10,4%), e depressão/ansiedade (9,1% e 11,7%), nos PS e TI, respectivamente. A região com maior frequência foi a sudeste onde concentra-se o maior contingente de trabalhadores. A FT acometida com alta carga de doenças crônicas não transmissíveis e exposta ao SARS-CoV-2, torna-se vulnerável para o adoecimento e morte. Sintomas mentais e intenso sofrimento psíquico foram relatados. Os resultados deste estudo nos permitem estimar o impacto na saúde física e mental, e nas condições de vida e de trabalho da FT. A saúde e a vida dos trabalhadores, protagonistas no enfrentamento dos desafios da pandemia, são prioridade nas políticas públicas.

COVID-19 and health systems in Brazil and around the world: effects on the working conditions and health of health workers. / COVID-19 e os sistemas de saúde do Brasil e do mundo: repercussões das condições de trabalho e de saúde dos profissionais de saúde.

This article discusses the impacts of the COVID-19 pandemic on health systems and its effects on the working conditions and mental health of health professionals and invisible health workers. It presents data on deaths among health professionals, highlighting the need for better and safer working conditions and improvements in public management. We emphasize WHO/PAHO recommendations and the need for equitable vaccine distribution, including poor countries and vulnerable populations. We also highlight the impacts of interrupting essential health services, such as the treatment of chronic conditions and infectious disease prevention, and the damage caused by the dissemination of fake news, stressing the need to improve access to correct and safe health information.

Este artigo apresenta os impactos da pandemia nos sistemas de saúde e as repercussões nas condições de trabalho e saúde mental dos profissionais de saúde e trabalhadores invisíveis da saúde no contexto da COVID-19. Apresenta a mortalidade entre os profissionais da saúde destacando a necessidade de melhores condições de trabalho e de segurança para os trabalhadores da saúde e melhora da gestão pública. Enfatiza as recomendações da OMS/OPAS, a necessidade de vacinação equânime, incluindo os países mais pobres e as populações mais vulneráveis. Relata os impactos da interrupção dos serviços essenciais em saúde, como para as doenças crônicas e infecciosas, e os prejuízos causados pela disseminação de informações falsas pela rede social, e lembra da necessidade de veiculação de informações corretas e seguras na saúde.

Colon Adenoma After Diagnosis of Immune Checkpoint Inhibitor-mediated Colitis.

Purpose: While the occurrence of colitis during immune checkpoint inhibitor (ICI) treatment is recognized as a sign of robust immune activation and correlates with better oncological outcomes, the long-term impact of ICI-mediated colitis on the colonic mucosa has not been studied. We thus aim to describe the colonoscopy and histology findings in patients at a follow-up time of ≥ 6 months post initial colitis event. Methods: This retrospective analysis included adult cancer patients diagnosed with ICI colitis at a tertiary cancer center between October 2013 and June 2020. The study group included patients diagnosed with immune mediated colitis who had also undergone a follow up colonoscopy or flex sigmoidoscopy. The control group was patients exposed to ICI without immune mediated colitis. We reported patients' colitis clinical course, treatment, outcomes, and endoscopic and histologic features at diagnosis and at follow-up time of ≥ 6 months. Results: Total 39 patients met the study criteria, with 82% being male, and 35.8% having melanoma. Most patients received a combination of CTLA-4 and PD-1/L1 inhibitors (82%). On initial endoscopic evaluation, inflammation without ulceration was reported in 76.9% of patients and active inflammation on histologic examination in 79.3% of patients. Most patients (79.4%) received corticosteroids, and 56.4% received add-on selective immunosuppressive therapy. Four patients received fecal microbiota transplantation. On follow-up, new incidence of colonic polyps was reported in 51.2% of patients, including adenomas in 33.3% among the colitis patients with median follow up duration of 12 months. The incidence of adenoma polyps 12 months after the colitis event was significantly higher compared to the control group without colitis based on the time-to-event analysis (p=0.041). Conclusion: At a median follow up of 12 months after their initial colitis diagnosis, 51.2% of the patients had new incidence of colonic polyps, including a third with adenoma, at a significantly higher incidence than the control group without colitis. Studies with larger sample sizes are needed to further define the long-term impact of colitis and its treatments on colon health and to refine recommendations for surveillance of colonic adenomas and colorectal cancer.

Transformações no mundo do trabalho em saúde: os(as) trabalhadores(as) e desafios futuros / Transformations in the world of healthcare work: workers and future challenges

Resumo O artigo versa sobre o mundo do trabalho da saúde, especialmente no SUS no contexto da pandemia no Brasil. O artigo utilizou dados das pesquisas "Condições de trabalho dos profissionais de saúde no contexto da COVID-19 no Brasil" e "Os trabalhadores invisíveis da saúde: condições de trabalho e saúde mental no contexto da COVID-19 no Brasil". A análise dos dados comprova que a pandemia evidenciou problemas estruturais existentes no âmbito do Sistema Único de Saúde, envolvendo a gestão da FTS o que pode ser interpretado como mais um dos reflexos das desigualdades socioeconômicas já existentes no país. Destacam-se: a reduzida oferta de educação permanente, a regulação do cuidado híbrido, precarização, desproteção no ambiente de trabalho, frágil biossegurança levando a trágicas taxas de adoecimento e mortes de trabalhadores da saúde. Conclui mostrando a importância de formulação de políticas públicas no âmbito da gestão da educação e do trabalho no SUS que assegurem a discussão sobre cuidado híbrido como nova forma de atuar sem perder qualidade, a necessidade de se rever questões referentes a: educação permanente, proteção, valorização e redução das desigualdades apontadas entre os contingentes profissionais analisados nesse artigo.

Abstract This article addresses the world of healthcare work, especially in the Brazilian Unified Healthcare System (SUS) in the context of the COVID-19 pandemic in Brazil. This study used data from the following surveys: "Working conditions of health professionals in the context of COVID-19 in Brazil" and "The Invisible health workers: working conditions and mental health in the context of COVID-19 in Brazil". Data analysis proves that the pandemic highlighted existing structural problems within SUS, involving the issue of healthcare workforce (HWF) management, which can be interpreted as another reflection of the socioeconomic inequalities that already exist in the country. This article highlights: the reduced provision of permanent education, the regulation of hybrid care, precariousness, a lack of protection in the work environment, as well as fragile biosecurity leading to tragic rates of illness and death of health workers. Our study concludes by showing the importance of formulating public policies in the scope of education and work management in SUS that ensure the discussion on hybrid care as a new way of acting without losing quality, together with the need to review issues related to permanent education, protection, valuation, and reduction of inequalities pointed out among the professional contingents analyzed in this article.

COVID-19 e os sistemas de saúde do Brasil e do mundo: repercussões das condições de trabalho e de saúde dos profissionais de saúde / COVID-19 and health systems in Brazil and around the world: effects on the working conditions and health of health workers

Resumo Este artigo apresenta os impactos da pandemia nos sistemas de saúde e as repercussões nas condições de trabalho e saúde mental dos profissionais de saúde e trabalhadores invisíveis da saúde no contexto da COVID-19. Apresenta a mortalidade entre os profissionais da saúde destacando a necessidade de melhores condições de trabalho e de segurança para os trabalhadores da saúde e melhora da gestão pública. Enfatiza as recomendações da OMS/OPAS, a necessidade de vacinação equânime, incluindo os países mais pobres e as populações mais vulneráveis. Relata os impactos da interrupção dos serviços essenciais em saúde, como para as doenças crônicas e infecciosas, e os prejuízos causados pela disseminação de informações falsas pela rede social, e lembra da necessidade de veiculação de informações corretas e seguras na saúde.

Abstract This article discusses the impacts of the COVID-19 pandemic on health systems and its effects on the working conditions and mental health of health professionals and invisible health workers. It presents data on deaths among health professionals, highlighting the need for better and safer working conditions and improvements in public management. We emphasize WHO/PAHO recommendations and the need for equitable vaccine distribution, including poor countries and vulnerable populations. We also highlight the impacts of interrupting essential health services, such as the treatment of chronic conditions and infectious disease prevention, and the damage caused by the dissemination of fake news, stressing the need to improve access to correct and safe health information.

Comorbidades e saúde mental dos trabalhadores da saúde no Brasil. O impacto da pandemia da COVID-19 / Comorbities and mental health among healthcare workers in Brazil. The impact of the COVID-19 pandemic

Resumo Trata-se de um artigo original que aborda a força de trabalho (FT) em saúde no Brasil, suas comorbidades e alterações da saúde mental na pandemia da COVID-19. O estudo conduzido pela Fundação Oswaldo Cruz coletou dados por meio de questionário on-line com um total de 36.612 participantes: profissionais de saúde (PS, formação de nível superior), e trabalhadores invisíveis (TI, nível técnico). A prevalência de comorbidades no Brasil foi de 26,1% e 23,9%, a maior foi hipertensão arterial (27,4% e 31,9%), seguida da obesidade (18,4% e 15,1%), doenças crônicas respiratórias (15,7% e 12,9%), diabetes mellitus (10,3% e 10,4%), e depressão/ansiedade (9,1% e 11,7%), nos PS e TI, respectivamente. A região com maior frequência foi a sudeste onde concentra-se o maior contingente de trabalhadores. A FT acometida com alta carga de doenças crônicas não transmissíveis e exposta ao SARS-CoV-2, torna-se vulnerável para o adoecimento e morte. Sintomas mentais e intenso sofrimento psíquico foram relatados. Os resultados deste estudo nos permitem estimar o impacto na saúde física e mental, e nas condições de vida e de trabalho da FT. A saúde e a vida dos trabalhadores, protagonistas no enfrentamento dos desafios da pandemia, são prioridade nas políticas públicas.

Abstract This is an original article that addresses the healthcare workforce (HW) in Brazil, as well as comorbidities and mental health changes during the COVID-19 pandemic. This study was conducted by the Oswaldo Cruz Foundation and collected data through an online questionnaires from a total of 36,612 participants, health professionals (HP, with higher education level), and invisible healthcare workers (IHW, with a technical mid-level education). The overall prevalence of comorbidities in Brazil was 26.1% and 23.9%; the highest was arterial hypertension (27.4% and 31.9%), followed by obesity (18.4% and 15.1%), chronic respiratory diseases (15.7% and 12.9%), diabetes mellitus (10.3% and 10.4%), and depression/anxiety (9.1% and 11.7%), in the HW and IHW, respectively. The region with the highest frequency was the southeast, where the largest contingent of workers is located. The HW, affected with a high burden of non-communicable chronic diseases and exposed to SARS-CoV-2, proved to be vulnerable to illness and death. Mental symptoms and intense psychological suffering have been reported. These results allow us to estimate the impacts upon physical and mental health, as well as upon living and working conditions of the HW. The health and life of workers, leading role in facing health challenges of the pandemic, are a high priority in public policies.

Use of Telehealth Resources in Primary Care and Its Association with Facing the COVID-19 Pandemic in Minas Gerais, Brazil.

Introduction: Use of telehealth (TH) resources increased dramatically during the COVID-19 pandemic. This study set out to examine associations between the level of integration of TH resources and the level of Primary Health Care (PHC) structuring to deal with the COVID-19 pandemic in the State of Minas Gerais, Brazil. Methods: This work was a cross-sectional study conducted through the application of a semistructured questionnaire to a sample of 260 PHC Teams working in the state of Minas Gerais, Brazil, from September to December 2020. This study was approved by the Research Ethics Committee and logged under report number 44.294.637. Results: Two variables were created - Level of the PHC structuring to deal with the COVID-19 pandemic and Level of TH structuring. Variables were grouped into five categories (poor to excellent). Associations between variables were examined using the Tukey's test for multiple comparisons and the Spearman correlation coefficient. Variables associated with socioeconomic dimensions (human development index and Gini index) and health care were also analyzed. Levels of TH structuring in PHC ranged from poor (43%) to regular (40%) in most cases. Most PHC teams had regular (56%) or good (37%) levels of PHC structuring to deal with the pandemic. The greater the availability and use of TH resources at a given unit, the better the structure to face COVID-19 (0.45 - p < 0.001). Conclusion: PHC was structured to tackle the pandemic. However, there is a lot to be done before TH resources are effectively incorporated into PHC. Whenever incorporated, TH resources contributed to a more robust response to the COVID-19 pandemic.

Adverse Events of Latent Tuberculosis Treatment With Isoniazid in People Living With HIV: A Case-Control Study in a Resource-Rich Setting.

Introduction Multiple risk factors, such as human immunodeficiency virus (HIV) infection and immunosuppressive therapies, increase the odds of latent tuberculosis infection (LTBI) reactivation and progression to active tuberculosis. A six-to-nine-month preventive treatment with isoniazid (INH) decreases the risk of LTBI reactivation, but its effectiveness can be limited by its long duration and adverse events (AEs), including liver toxicity. Due to comorbidities and polypharmacy, people living with HIV (PLHIV) may be at increased risk of INH-associated AEs. Our study aimed to assess the prevalence of AEs among patients receiving INH treatment for LTBI, to identify risk factors for their occurrence, and to evaluate whether PLHIV have higher odds of developing INH-associated AEs. Methods We conducted a single-center retrospective case-control study, including 130 outpatients with LTBI treated with INH between July 2019 and March 2022. Participants who developed AE (cases) were compared to controls, and a subgroup of PLHIV was compared to HIV-negative participants. Demographics, socioeconomic variables, comorbidities, and clinical variables were compared between study groups. Patient data were obtained from institutional electronic medical records, and outcomes were measured at regularly scheduled appointments. Results We included 130 participants, of which 54 were PLHIV. The PLHIV subgroup was significantly younger (p = 0.01) and demonstrated significantly higher prevalences of chronic liver disease, previous viral hepatitis, daily alcohol consumption, and intravenous drug use (IDU). One-third of the participants had an AE (45 cases, 34.6%), with liver toxicity being the most common (22.3%). Participants who developed AEs were significantly older (p = 0.030) and had a higher prevalence of economic hardship (p = 0.037), as well as higher scores of the Charlson comorbidity index (p = 0.002) than the controls. INH withdrawal occurred in 17 participants (13.1%) and was mainly associated with liver toxicity (p < 0.01) and gastrointestinal symptoms (p = 0.022). In the adjusted effect model, an age ≥ 65 years, economic hardship, and excessive alcohol consumption were significantly associated with higher odds of AEs, while HIV infection decreased the odds by 68.4% (p = 0.033). Conclusions In our study, INH-associated AEs were common, with liver toxicity being the most frequent. Older age, economic hardship, and excessive alcohol consumption increased the odds of INH-associated AEs, while PLHIV had lower odds of developing INH-associated AEs, even when adjusting for other variables in the multivariate analysis. Further studies should be conducted to assess if these results are replicable in a larger population and in different settings.

Role of C-Reactive Protein in Predicting the Severity and Response of Immune-Mediated Diarrhea and Colitis in Patients with Cancer.

Background: Immune-mediated diarrhea and colitis (IMDC) frequently develop after treatment with immune checkpoint inhibitors. C-reactive protein (CRP) is a serum inflammatory biomarker used to stratify and monitor disease severity in many inflammatory conditions. However, CRP level is not specific and is widely influenced by various factors non-specific to bowel inflammation. We aimed to study the utility of CRP as a predictor of disease severity and therapy response in IMDC. Methods: We performed a retrospective analysis of patients diagnosed with IMDC who had CRP measured at IMDC onset and after treatment with selective immunosuppressive therapy (SIT: infliximab and vedolizumab), between 01/2016 and 02/2022 at MD Anderson Cancer Center. Patient demographics, clinical characteristics, and IMDC data were collected and analyzed. Results: Our sample of 128 patients had a median age of 67 years; most were white (89.8%); and male (65.6%). Prior to development of IMDC, 15 (11.7%) were initially treated with anti-CTLA-4, 42 (32.8%) with anti-PD-1 or PD-L1, and 71 (55.5%) with a combination of both. We found higher CRP level was associated with higher CTCAE grade of clinical symptoms such as diarrhea (p=0.015), colitis (p=0.013), and endoscopic findings (p=0.016). While CRP levels decreased after IMDC treatment, there was no significant association between CRP levels with clinical remission, endoscopic remission or histologic remission. There also was no significant correlation between CRP level and recurrence of IMDC, or with fecal calprotectin levels. Conclusion: CRP level may be useful to assess initial severity of IMDC, including grade of diarrhea and colitis and degree of endoscopic inflammation. However, CRP is not a robust surrogate biomarker for assessing treatment response or disease recurrence. Despite the reduction of CRP levels observed following IMDC treatment, this finding might be nonspecific and potentially confounded by concurrent clinical factors, such as underlying malignancy, other inflammatory processes, and systemic anti-cancer therapy. Further studies of the role of CRP are warranted in patients with cancer and IMDC.

Evaluation of the polyphenolic profile of native Ecuadorian stingless bee honeys (Tribe: Meliponini) and their antibiofilm activity on susceptible and multidrug-resistant pathogens: An exploratory analysis.

Biofilms are associated with infections that are resistant to conventional therapies, contributing to the antimicrobial resistance crisis. The need for alternative approaches against biofilms is well-known. Although natural products like stingless bee honeys (tribe: Meliponini) constitute an alternative treatment, much is still unknown. Our main goal was to evaluate the antibiofilm activity of stingless bee honey samples against multidrug-resistant (MDR) pathogens through biomass assays, fluorescence (cell count and viability), and scanning electron (structural composition) microscopy. We analyzed thirty-five honey samples at 15% (v/v) produced by ten different stingless bee species (Cephalotrigona sp., Melipona sp., M. cramptoni, M. fuscopilosa, M. grandis, M. indecisa, M. mimetica, M. nigrifacies, Scaptotrigona problanca, and Tetragonisca angustula) from five provinces of Ecuador (Tungurahua, Pastaza, El Oro, Los Ríos, and Loja) against 24-h biofilms of Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, and Candida tropicalis. The present honey set belonged to our previous study, where the samples were collected in 2018-2019 and their physicochemical parameters, chemical composition, mineral elements, and minimal inhibitory concentration (MIC) were screened. However, the polyphenolic profile and their antibiofilm activity on susceptible and multidrug-resistant pathogens were still unknown. According to polyphenolic profile of the honey samples, significant differences were observed according to their geographical origin in terms of the qualitative profiles. The five best honey samples (OR24.1, LR34, LO40, LO48, and LO53) belonging to S. problanca, Melipona sp., and M. indecisa were selected for further analysis due to their high biomass reduction values, identification of the stingless bee specimens, and previously reported physicochemical parameters. This subset of honey samples showed a range of 63-80% biofilm inhibition through biomass assays. Fluorescence microscopy (FM) analysis evidenced statistical log reduction in the cell count of honey-treated samples in all pathogens (P <0.05), except for S. aureus ATCC 25923. Concerning cell viability, C. tropicalis, K. pneumoniae ATCC 33495, and K. pneumoniae KPC significantly decreased (P <0.01) by 21.67, 25.69, and 45.62%, respectively. Finally, scanning electron microscopy (SEM) analysis demonstrated structural biofilm disruption through cell morphological parameters (such as area, size, and form). In relation to their polyphenolic profile, medioresinol was only found in the honey of Loja, while scopoletin, kaempferol, and quercetin were only identified in honey of Los Rios, and dihydrocaffeic and dihydroxyphenylacetic acids were only detected in honey of El Oro. All the five honey samples showed dihydrocoumaroylhexose, luteolin, and kaempferol rutinoside. To the authors' best knowledge, this is the first study to analyze stingless bees honey-treated biofilms of susceptible and/or MDR strains of S. aureus, K. pneumoniae, and Candida species.

Identification and validation of the first EST-SSR markers based on transcriptome of Anopheles darlingi, the primary transmitter of malaria in Brazil.

BACKGROUND: Anopheles darlingi is a monotypic species in terms of its morphological, genetic, and behavioral aspects and is the primary transmitter of human malaria (99%) in Brazil, especially in the Brazilian Amazon. In this pioneering study, 15 expressed sequence tag (EST)-simple sequence repeat (SSR) markers were obtained and characterized in samples from the municipality of São Gabriel da Cachoeira, Amazonas state, Brazil, with polymorphisms that can be used for further genetic research. METHODS AND RESULTS: The specimens (from egg to larval stage) collected were bred in the insectary at INPA (National Institute for Amazonian Research). The SSR repeats within the contigs of the A. darlingi EST banks were confirmed on the Vector Base site. DNA was extracted and amplified using polymerase chain reaction and then genotyped. Fifteen polymorphic SSR loci were identified and characterized. The number of alleles totaled 76 and ranged from 2 to 9. The observed heterozygosity varied between 0.026 and 0.769, the expected heterozygosity between 0.025 and 0.776, and the mean polymorphism information content was 0.468. Eight loci showed Hardy-Weinberg equilibrium (HWE) after Bonferroni correction (P: (5%) ≤ 0.0033). No linkage disequilibrium was found among the loci. CONCLUSIONS: The polymorphic SSRs of the loci have been shown to be efficient for investigation of the variability and genetic population structure of A. darlingi.

Impact of Selective Immunosuppressive Therapy on Subsequent Immune-Related Adverse Events After Immune Checkpoint Inhibitor-Induced Colitis Treatment.

OBJECTIVES: Immune checkpoint inhibitors (ICI) can cause immune-related adverse events (irAEs) such as colitis. irAEs can be managed by selective immunosuppressive therapy (SIT) agents such as infliximab and vedolizumab. We aimed to elucidate the incidence of subsequent new irAEs after exposure to SIT by describing patients' clinical course. METHODS: We conducted a retrospective chart review of adult patients at a tertiary cancer center diagnosed with ICI-mediated colitis (IMC) treated with SIT from February 2013 through October 2021. Patients' clinical courses, treatments, and outcomes of new irAEs after SIT were collected and analyzed. RESULTS: The study included 156 patients. Most were male (67.3%), 44.8% had melanoma, and 43.5% received anti-PD1/L1 ICIs. For IMC treatment, 51.9% received infliximab and 37.8% received vedolizumab. Twenty-six patients (16.6%) resumed ICI treatment after their colitis event. Twenty-five patients (16%) developed a new irAE after receiving SIT. The most common new irAE involved skin (44%), and most (60%) were treated with steroids. Higher diarrhea grade and ≥2 doses of SIT were associated with lower incidence of post-SIT irAEs ( P =0.038, P =0.050). However, the type of SIT or individual dosage of infliximab did not affect the occurrence of subsequent irAEs. CONCLUSIONS: New irAEs usually occur more than 6 months after SIT completion for initial colitis event. Severe diarrhea grade and higher number of SIT infusions appeared to have protective effect to lower the occurrence of new irAEs. Otherwise, the type of SIT or individual dosage of infliximab did not affect the occurrence of subsequent irAEs.

Battle royale: Immune response on biofilms - host-pathogen interactions.

The research interest of the scientific community in biofilm-forming microorganisms is growing due to the problems caused by their infections affecting humans and animals, mainly because of the difficulty of the host immune system in eradicating these microbial complex communities and the increasing antimicrobial resistance rates worldwide. This review describes the virulence factors and their interaction with the microbial communities of four well-known and highly biofilm-forming pathogens, more exactly, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus spp., and Candida spp. The innate and adaptive immune responses caused by the infection with these microorganisms and their evasion to the host immune system by biofilm formation are discussed in the present work. The relevance of the differences in the expression of certain virulence factors and the immune response in biofilm-associated infections when compared to planktonic infections is usually described as the biofilm architecture protects the pathogen and alters the host immune responses, here we extensively discussed these mechanisms.

Superconductivity in Te-Deficient ZrTe2.

We present structural, electrical, and thermoelectric potential measurements on high-quality single crystals of ZrTe1.8 grown from isothermal chemical vapor transport. These measurements show that the Te-deficient ZrTe1.8, which forms the same structure as the nonsuperconducting ZrTe2, is superconducting below 3.2 K. The temperature dependence of the upper critical field (H c2) deviates from the behavior expected in conventional single-band superconductors, being best described by an electron-phonon two-gap superconducting model with strong intraband coupling. For the ZrTe1.8 single crystals, the Seebeck potential measurements suggest that the charge carriers are predominantly negative, in agreement with the ab initio calculations. Through first-principles calculations within DFT, we show that the slight reduction of Te occupancy in ZrTe2 unexpectedly gives origin to density of states peaks at the Fermi level due to the formation of localized Zr-d bands, possibly promoting electronic instabilities at the Fermi level and an increase at the critical temperature according to the standard BCS theory. These findings highlight that the Te deficiency promotes the electronic conditions for the stability of the superconducting ground state, suggesting that defects can fine-tune the electronic structure to support superconductivity.