Antimicrobial resistance, enterotoxin and biofilm production genes in Staphylococcus spp. isolated from facilities and fomites in veterinary hospital in the Caatinga biome.

The Caatinga biome occurs only in Brazil and offers epidemiological conditions that should be assessed differently from other regions of Brazil and the world. Thus, the aim of this survey was to identify antimicrobial resistance, enterotoxin and biofilm production genes in Staphylococcus spp. isolated from facilities and fomites in a veterinary hospital in Caatinga biome. Samples were collected from surfaces of small animal clinical care tables (n =8), cages in the dog and cat hospitalisation sector and animals with infectious diseases (n = 21), small animal surgical centre (n =8), sterilisation sector (n =7) and stethoscopes (n = 32) by using sterile swabs. Bacterial isolation and identification, antimicrobial resistance phenotypic test and molecular detection of antimicrobial resistance, biofilm formation and enterotoxin genes were carried out. Ninety-five bacterial isolates were obtained, and 29 (30.5%) were identified as Staphylococcus spp. Overall, 13 isolates (44.8%) of six species of Staphylococcus spp. showed antimicrobial resistance profile, as well as S. haemolyticus expressed phenotypic profile of multidrug resistance. The antimicrobials with the highest resistance rates were penicillin and tetracycline. The most frequent resistance genes were blaZ and tetM, both detected in 10 (76.9%) isolates. The mecA, tetL and tetK genes had frequencies of 38.5% (5/13), 23.1% (3/13) and 15.4% (2/13), respectively. The biofilm production marker, icaD gene, was detected in one S. sciuri strain. SEE gene, which encodes enterotoxins, was detected in 15.4% (2/13) of the strains (S. pseudintermedius and S. intermedius). The occurrence of Staphylococcus spp. carrying resistance genes to diferent classes of antimicrobials, presenting MDR phenotypic pattern and carrying enterotoxins and biofim encoding genes recovered from veterinary hospital facilities and fomites in the Caatinga biome reinforce the need to implement prevention cares in veterinary practices to avoid One Health-concerning conditions.

Epidemiological and clinicopathological findings of feline immunodeficiency virus and feline leukemia virus infections in domestic cats from the Brazilian semiarid region.

Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are retroviruses of great importance for domestic cats with a worldwide distribution. A retrospective study was conducted to determine the epidemiological and clinicopathological aspects of the infection by FIV and FeLV in cats from the Brazilian semiarid region. Cats treated between 2011 and 2021 at the teaching veterinary hospital of the Federal Rural University of the Semi-Arid Region that were submitted to a point-of-care (POC) test to detect anti-FIV IgG antibodies and FeLV antigen were enrolled in the study. Overall, 454 cats were selected, of which 30.2% [95% CI = 26.0% - 34.3%] were FIV-positive, 1.1% [95% CI = 0.9% - 1.2%] were FeLV-positive, and 0.7% [95% CI = 0.1% - 1.3%] were coinfected by both retroviruses. No statistical association was found between the studied retroviruses (P = 0.144). Multivariable analysis detected significant associations between FIV infection and male sex [OR = 5.7, 95% CI = 3.0-10.7, P < 0.0001), age between 19 and 78 months [OR = 5.2, 95% CI = 2.2-12.1, P < 0.0001], age greater than 78 months [OR = 12.8, 95% CI = 5.1-31.9, P < 0.0001], crossbreed [OR = 4.1, 95% CI = 1.2-13.4, P = 0.021], the presence of oral disease [OR = 2.1, 95% CI = 1.3-3.4, P = 0.004], reduced red blood cell (RBC) count [OR = 3.7, 95% CI = 1.9-7.2, P < 0.0001], and an albumin:globulin (A:G) ratio lower than 0.6 [OR = 3.4, 95% CI = 1.6-7.1, P = 0.001]. No statistical analyses were performed for FeLV infection due to the low number of positive animals. In the quantitative analyses of hematological parameters, FIV-positive cats presented lower values for RBC, hemoglobin, hematocrit, lymphocytes, and platelets compared to the negative animals. In the biochemical profile, cats infected with FIV showed higher creatinine, urea, total protein, and globulin values, while lower values for albumin and A:G ratio were observed (P < 0.05). The findings of this study characterized the prevalence, clinicopathological findings, and risk factors associated with FIV and FeLV in cats from the Brazilian semiarid region. They may help support veterinary practitioners in diagnosing feline retroviruses. The FIV prevalence observed is among the highest reported in Brazil, demonstrating the need for prevention and control strategies for this retrovirus.

Vitiligo-like Lesions as a Predictor of Response to Immunotherapy in Non-Small Cell Lung Cancer: Comprehensive Review and Case Series from a University Center.

The reference to vitiligo-like lesions (VLLs) induced by immune checkpoint inhibitors (ICIs) as a valuable predictive marker of treatment success of immunotherapy with ICIs in melanoma has been mentioned in the literature. Its role in non-small cell lung cancer (NSCLC)-treated patients remains a poorly recognized phenomenon with uncertain significance regarding its predictive value. A retrospective, observational, single-center report was performed, with descriptive analysis of clinicopathological and treatment characteristics of patients with stage IV NSCLC who developed ICI-induced VLL between January 2018 and December 2022, contextualized in a comprehensive review of the literature and reported cases regarding this phenomenon. During the first 5 years' experience of ICI use in stage IV NSCLC treatment, three cases of ICI-induced VLLs were diagnosed. In line with the previous reports, two of the three presented cases exhibited treatment response and favorable prognosis. The recognition and understanding of the pathophysiological processes underlying ICI-induced VLLs may represent a promising opportunity to identify a predictive marker of tumor response to ICIs, with impact in treatment selection and patient management. It also may contribute to the recognition of new patterns of molecular expression that could lead to improvements in therapeutic development.

What's new about the tumor microenvironment of urothelial carcinoma?

Urothelial carcinoma is a significant global health concern that accounts for a substantial part of cancer diagnoses and deaths worldwide. The tumor microenvironment is a complex ecosystem composed of stromal cells, soluble factors, and altered extracellular matrix, that mutually interact in a highly immunomodulated environment, with a prominent role in tumor development, progression, and treatment resistance. This article reviews the current state of knowledge of the different cell populations that compose the tumor microenvironment of urothelial carcinoma, its main functions, and distinct interactions with other cellular and non-cellular components, molecular alterations and aberrant signaling pathways already identified. It also focuses on the clinical implications of these findings, and its potential to translate into improved quality of life and overall survival. Determining new targets or defining prognostic signatures for urothelial carcinoma is an ongoing challenge that could be accelerated through a deeper understanding of the tumor microenvironment.

Distribution, seroprevalence and risk factors for bovine brucellosis in Brazil: Official data, systematic review and meta-analysis.

Bovine brucellosis is an endemic disease in Brazil, and evidence-based assessments of the available literature on its seroprevalence and risk factors are limited. The aim of this study was to systematically review and summarize studies related to seroprevalence and risk factors of bovine brucellosis in the entire Brazil, in addition to comparing published data with the most recent official reports. Articles available in scientific databases and published between October 2006 and October 2021 were evaluated. Forty-five publications were included in the meta-analysis on the seroprevalence of brucellosis and 29 publications in the review on risk factors. The largest number of publications was found for the State of Mato Grosso do Sul (n=4), and the highest and lowest seroprevalences were observed in Acre (11%; 95% CI: 8.0-14.0%) and in the Federal District (0.4%; 95% CI: 0.2-0.7%). The main risk factors were the purchase of animals for breeding, vaccination, the number of heifers (female ≥2 years), the presence of calving paddocks and the occurrence of abortions. The need for new official studies has been suggested to determine the true prevalence of bovine brucellosis in Brazil, supported by the National Program for the Control and Eradication of Animal Brucellosis and Tuberculosis.

Plain language summary of the HIMALAYA study: tremelimumab and durvalumab for unresectable hepatocellular carcinoma (liver cancer).

WHAT IS THIS SUMMARY ABOUT?: This is a summary of results from a phase 3 clinical study called HIMALAYA. HIMALAYA looked at treatment with one dose of a medication called tremelimumab combined with multiple doses of a medication called durvalumab (the STRIDE regimen) or multiple doses of durvalumab alone. These treatments were compared with a medication called sorafenib in participants with unresectable hepatocellular carcinoma (HCC). HCC is a type of liver cancer that is difficult to treat because it is often diagnosed when it is unresectable, meaning it can no longer be removed with surgery. Sorafenib has been the main treatment for unresectable HCC since 2007. However, people who take sorafenib may experience side effects that can reduce their quality of life, so alternative medicines are being trialed. Tremelimumab and durvalumab are types of drugs called immunotherapies, and they both work in different ways to help the body's immune system fight cancer. WHAT WERE THE RESULTS OF THE STUDY?: Participants who took STRIDE lived longer than participants who took sorafenib, whilst participants who took durvalumab alone lived a similar length of time as participants who took sorafenib. Participants who took STRIDE or durvalumab had a lower relative risk of experiencing worsening in their quality of life than participants who took sorafenib. The side effects that participants who received STRIDE or durvalumab experienced were expected for these types of treatments and could mostly be managed. WHAT DO THE RESULTS OF THE STUDY MEAN?: Overall, STRIDE is more effective than sorafenib for people with unresectable HCC.

Strong Evidence of the Role of Donkeys in the Epidemiology of Leptospira spp. in Semiarid Conditions.

Donkeys (Equus asinus) are historically known for their close relationship to humanity, which raises the need to study zoonotic diseases that affect them. In this perspective, leptospirosis stands out as a disease with an economic and public health impact, and its occurrence is facilitated in times of higher rainfall indexes, especially in large urban centers. In view of the scarcity of information about leptospirosis in donkeys, the objective of this study was to detect the presence of Leptospira spp. and anti-leptospiral antibodies in donkeys rescued by a zoonosis center located in the Caatiga biome, Brazilian semiarid region. Overall, 30 donkeys of both sexes, aged between 4 months and 15 years, were used, from which 64 serum samples were collected and submitted to the microscopic agglutination test (MAT). In addition, 64 samples of urine, vaginal and preputial fluid, in duplicates, were subjected to the polymerase chain reaction (PCR) and microbiological. Sixteen (53.3%) animals tested positive in at least one diagnostic test, 12 (40%) of which were positive at MAT and seven (23.3%) in the molecular and bacteriological detection (urine, vaginal, and preputial fluid samples). This is the first report identifying donkeys infected with Leptospira spp. by molecular and bacteriological diagnosis in Brazil, and the first in the world to detect this agent in their genital fluids. The study also shows that donkeys are commonly exposed to leptospires in the Caatinga biome, and this constitutes a One Health-based concern, demonstrating the importance of broad studies where large numbers of humans and animals coexist when investigating zoonotic infections and when planning and implementing control measures for donkeys-associated leptospirosis.

Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study.

BACKGROUND: Targeted therapy and immunotherapy have shown intracranial activity in melanoma with CNS metastases, but there remains an unmet need, particularly for patients with symptomatic CNS metastases. We aimed to evaluate atezolizumab in combination with cobimetinib or vemurafenib plus cobimetinib in patients with melanoma with CNS metastases. METHODS: TRICOTEL was a multicentre, open-label, single-arm, phase 2 study done in two cohorts: a BRAFV600 wild-type cohort and a BRAFV600 mutation-positive cohort, recruited at 21 hospitals and oncology centres in Brazil, France, Germany, Hungary, Italy, Spain, and Switzerland. Eligible patients were aged 18 years or older with previously untreated metastatic melanoma, brain metastases of 5 mm or larger in at least one dimension, and an Eastern Cooperative Oncology Group performance status of 2 or less. Patients in the BRAFV600 wild-type cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral cobimetinib (60 mg once daily, days 1-21). Patients in the BRAFV600 mutation-positive cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral vemurafenib (720 mg twice daily) plus oral cobimetinib (60 mg once daily, days 1-21); atezolizumab was withheld in cycle 1. Treatment was continued until progression, toxicity, or death. The primary outcome was intracranial objective response rate confirmed by assessments at least 4 weeks apart, as assessed by independent review committee (IRC) using modified Response Evaluation Criteria in Solid Tumours version 1.1. Because of early closure of the BRAFV600 wild-type cohort, the primary endpoint of intracranial objective response rate by IRC assessment was not done in this cohort; intracranial objective response rate by investigator assessment was reported instead. Efficacy and safety were analysed in all patients who received at least one dose of study medication. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT03625141. FINDINGS: Between Dec 13, 2018, and Dec 7, 2020, 65 patients were enrolled in the BRAFV600 mutation-positive cohort; the BRAFV600 wild-type cohort was closed early after enrolment of 15 patients. Median follow-up was 9·7 months (IQR 6·3-15·0) for the BRAFV600 mutation-positive cohort and 6·2 months (3·5-23·0) for the BRAFV600 wild-type cohort. Intracranial objective response rate was 42% (95% CI 29-54) by IRC assessment in the BRAFV600 mutation-positive cohort and 27% (95% CI 8-55) by investigator assessment in the BRAFV600 wild-type cohort. Treatment-related grade 3 or worse adverse events occurred in 41 (68%) of 60 patients who received atezolizumab plus vemurafenib plus cobimetinib in the BRAFV600 mutation-positive cohort, the most common of which were lipase increased (15 [25%] of 60 patients) and blood creatine phosphokinase increased (11 [18%]). Eight (53%) of 15 patients treated with atezolizumab plus cobimetinib in the BRAFV600 wild-type cohort had treatment-related grade 3 or worse adverse events, most commonly anaemia (two [13%]) and dermatitis acneiform (two [13%]). Treatment-related serious adverse events occurred in 14 (23%) of 60 patients who received triplet therapy in the BRAFV600 mutation-positive cohort and two (13%) of 15 in the BRAFV600 wild-type cohort. No treatment-related deaths occurred. INTERPRETATION: Atezolizumab plus vemurafenib and cobimetinib provided intracranial activity in patients with BRAFV600-mutated melanoma with CNS metastases. FUNDING: F Hoffmann-La Roche.

Determination of pathogens and contamination indicatorsin fresh pork sausages in the state of São Paulo / Determinação de patógenos e indicadores de contaminação em linguiças frescais de origem suína no estado de São Paulo

The highest cost of beef and chicken meat justifies higher consumption of fresh sausage products, especially linguiça, due to their easy preparation and affordability for consumers, making necessary an evaluation of sanitary hygienic conditions of these products. The objective was to investigate the presence of pathogens such as Salmonella spp., coagulase-positive Staphylococcus, thermotolerant coliforms, Escherichia coli and Campylobacter spp. in artisanal and inspected fresh pork sausages. It was found that 12% (6/50) of the artisanal sausage samples were contaminated with Salmonellaspp., 58% (29/50) presented coagulase-positive Staphylococcus levels above the acceptable limits for consumption and 76% (38/50) presented thermotolerant coliform levels above the acceptable limits. In sausage samples produced under inspected conditions, 6% (3/50) were contaminated with Salmonella spp., 24% (12/50) presented thermotolerant coliform levels above the acceptable limits, 2% (1/50) presented enteropathogenic E. coli. None samples showed coagulase-positive Staphylococcus counts above the limits, or presence of Campylobacter spp. Sensitizing traders and consumers about the importance of inspection service in food of animal origin is urgent for a sanitary acceptable production, since foodborne diseases continue to be a public health problem.

O alto custo das carnes de frango e bovina justifica maior consumo de produtos embutidos frescais, especialmente a linguiça, devido ao preço acessível ao consumidor e fácil preparo, tornando necessário estudos para avaliar as condições higiênico-sanitárias. Os objetivos foram verificar a presença de Salmonella spp., Staphylococcus coagulase positiva, coliformes termotolerantes, Escherichia colipatogênicas e Campylobacter spp. em linguiças suínas tipo frescal artesanais e fiscalizadas. Os resultados obtidos em linguiças artesanais foram de 12% (6/50) contaminadas com Salmonella spp., 58% (29/50) de Staphylococcus coagulase positiva e 76% (38/50) nas quantificações de coliformes termotolerantes, dados que apresentam níveis de contaminação superiores aos da legislação vigente. Nas linguiças produzidas sob fiscalização detectou-se 6% (3/50) de contaminação por Salmonella spp.; 24% (12/50) de quantificação de coliformes termotolerantes acima dos limites aceitáveis, e 2% (1/50) de E. coli enteropatogênica. Nenhuma amostra apresentou contagens de Staphylococcus coagulase positiva fora dos padrões, ou contaminação por Campylobacter spp. Sensibilizar comerciantes e consumidores sobre a importância do serviço de inspeção em alimentos de origem animal é premente para que haja uma produção sanitária aceitável, pois doenças transmitidas por alimentos continuam sendo um problema à saúde pública.

Novel octa-graphene-like structures based on GaP and GaAs.

CONTEXT: The discovery of graphene gave way to the search for new two-dimensional structures. In this regard, octa-graphene is a carbon allotrope consisting of 4- and 8-membered rings in a single planar sheet, drawing the research community's attention to study their inorganic analogs. Considering the promising properties of octa-graphene-like structures and the role of GaAs and GaP in semiconductor physics, this study aims to propose, for the first time, two novel inorganics buckled nanosheets based on the octa-graphene structure, the octa-GaAs and octa-GaP. This work investigated the structural, electronic, and vibrational properties of these novel octa-graphene-based materials. The octa-GaP and octa-GaAs have an indirect band gap transition with a valence band maximum between M and Г points and a conduction band minimum at Г point with energy of 3.05 eV and 2.56 eV, respectively. The QTAIMC analysis indicates that both structures have incipient covalent in their bonds. The vibrational analysis demonstrates the occurrence of ΓRaman = 6Ag + 6Bg and ΓRaman = 12A' + 12B″ for octa-GaP and octa-GaAs, respectively. The symmetry reduction of octa-GaAs leads to activating inactive modes observed in the octa-GaP structure. The frontier crystalline orbitals are composed by Ga(px) and P(py and pz) orbitals for octa-GaP and Ga(px and py) and As(s, py, and pz) for octa-GaAs in the valence bands while in the conduction bands by Ga(py, pz, and s) for both compounds and P(px and pz) and As(py). The phonon bands demonstrate the absence of the negative frequency modes and the structural stability of these new nanosheets. This report aims to reveal the fundamental properties of both newfound materials for stimulating experimental research groups in the search for synthesis routes to obtain this structure. METHODS: This work used the DFT/B3LYP approach implemented in the CRYSTAL17 computational package. Ga, As, and P atomic centers were described by triple-zeta valence with polarization (TZVP) basis set. The vibrational analysis was carried out via coupled-perturbed Hartree-Fock/Kohn Sham (CPHF/KS) method, and the chemical bonds were evaluated via the quantum theory of atoms in molecules and crystals (QTAIMC).

Occurrence of IgG antibodies against Toxoplasma gondii, Neospora caninum, and Leptospira spp. in goats and sheep from an indigenous village in Pernambuco, Brazil.

This study aimed to determine the occurrence of anti-Toxoplasma gondii, Neospora caninum, and Leptospira spp. antibodies in sheep and goats raised in villages of the Xukuru do Ororubá indigenous community, Pernambuco, Brazil. A total of 180 serum samples from sheep and 108 serum samples from goats of both sexes and different ages were analyzed. For antibody research, indirect immunofluorescence antibody test (IFAT) were used for the protozoa T. gondii and N. caninum, and microscopic agglutination test (MAT) for Leptospira spp., with a cutoff titer of 1:64, 1:50 and 1:100, respectively. The frequency of anti-T. gondii antibodies was 16.6% (30/180) for sheep and 11.1% (12/108) for goats. The frequency of anti-N. caninum antibodies was 10.55% (19/180) for sheep, and 20.37% (22/108) for goats, while for Leptospira spp., 2.2% (4/180) of sheep and 1.85% (2/108) of goats reacted positively. The results obtained in this study are unprecedented in indigenous communities in the country and serve as an alert for monitoring goats and sheep from the Xukuru do Ororubá indigenous village regarding the occurrence and productive impact of infections by T. gondii, N. caninum, and Leptospira spp., in addition to the occurrence of the zoonosis toxoplasmosis and leptospirosis in the indigenous community.

Herd-level based seroprevalence and associated factors for Toxoplasma gondii in cows in the state of Paraíba, Northeastern Brazil.

We aimed to determine the herd and animal levels seroprevalence and associated factors for Toxoplasma gondii infections in cattle from the state of Paraíba, Northeastern Brazil. Herds (n = 434) and cows aged ≥ 24 months (n = 1,895) were randomly selected, and serum samples were tested with the immunofluorescence antibody test (IFAT) using as cutoff of 64. Of the 434 farms investigated, 197 had at least one seropositive cow (prevalence of 49.0%; 95% CI = 44.3%-53.8%), and the prevalence at animal level was 18.0% (95% CI = 5.3%-21.1%). The antibody titers ranged from 64 to 1024, with the most frequent titers being 64 (10.8%) and 128 (3.7%). The risk factors identified were property located in Sertão region (odds ratio [OR] = 3.07), property located in Agreste/Zona da Mata regions (OR = 2.00), animal purchasing (OR = 2.68), herd size of 34-111 animals (OR = 2.91) and herd size > 111 animals (OR = 6.97). The results suggest the wide distribution of T. gondii infections in cattle throughout the state of Paraíba, and the risk factors identified are not possible to correct.

Efficacy and Safety of Nivolumab Plus Ipilimumab vs Nivolumab Alone for Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: The Phase 2 CheckMate 714 Randomized Clinical Trial.

Importance: There remains an unmet need to improve clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Objective: To evaluate clinical benefit of first-line nivolumab plus ipilimumab vs nivolumab alone in patients with R/M SCCHN. Design, Setting, and Participants: The CheckMate 714, double-blind, phase 2 randomized clinical trial was conducted at 83 sites in 21 countries between October 20, 2016, and January 23, 2019. Eligible participants were aged 18 years or older and had platinum-refractory or platinum-eligible R/M SCCHN and no prior systemic therapy for R/M disease. Data were analyzed from October 20, 2016 (first patient, first visit), to March 8, 2019 (primary database lock), and April 6, 2020 (overall survival database lock). Interventions: Patients were randomized 2:1 to receive nivolumab (3 mg/kg intravenously [IV] every 2 weeks) plus ipilimumab (1 mg/kg IV every 6 weeks) or nivolumab (3 mg/kg IV every 2 weeks) plus placebo for up to 2 years or until disease progression, unacceptable toxic effects, or consent withdrawal. Main Outcomes and Measures: The primary end points were objective response rate (ORR) and duration of response between treatment arms by blinded independent central review in the population with platinum-refractory R/M SCCHN. Exploratory end points included safety. Results: Of 425 included patients, 241 (56.7%; median age, 59 [range, 24-82] years; 194 males [80.5%]) had platinum-refractory disease (nivolumab plus ipilimumab, n = 159; nivolumab, n = 82) and 184 (43.3%; median age, 62 [range, 33-88] years; 152 males [82.6%]) had platinum-eligible disease (nivolumab plus ipilimumab, n = 123; nivolumab, n = 61). At primary database lock, the ORR in the population with platinum-refractory disease was 13.2% (95% CI, 8.4%-19.5%) with nivolumab plus ipilimumab vs 18.3% (95% CI, 10.6%-28.4%) with nivolumab (odds ratio [OR], 0.68; 95.5% CI, 0.33-1.43; P = .29). Median duration of response for nivolumab plus ipilimumab was not reached (NR) (95% CI, 11.0 months to NR) vs 11.1 months (95% CI, 4.1 months to NR) for nivolumab. In the population with platinum-eligible disease, the ORR was 20.3% (95% CI, 13.6%-28.5%) with nivolumab plus ipilimumab vs 29.5% (95% CI, 18.5%-42.6%) with nivolumab. The rates of grade 3 or 4 treatment-related adverse events with nivolumab plus ipilimumab vs nivolumab were 15.8% (25 of 158) vs 14.6% (12 of 82) in the population with platinum-refractory disease and 24.6% (30 of 122) vs 13.1% (8 of 61) in the population with platinum-eligible disease. Conclusions and Relevance: The CheckMate 714 randomized clinical trial did not meet its primary end point of ORR benefit with first-line nivolumab plus ipilimumab vs nivolumab alone in platinum-refractory R/M SCCHN. Nivolumab plus ipilimumab was associated with an acceptable safety profile. Research to identify patient subpopulations in R/M SCCHN that would benefit from nivolumab plus ipilimumab over nivolumab monotherapy is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02823574.

Herd and animal level prevalences and risk factors for Neospora caninum infection in cattle in the state of Paraíba, northeastern Brazil.

Bovine neosporosis is a globally important disease, causing abortions and significant economic losses. In Brazil, studies on neosporosis in cattle are few and based on limited samples and/or from limited areas. We aimed to determine the herd and animal levels seroprevalence and associated factors for Neospora caninum infections in cattle from the state of Paraíba, Northeastern Brazil, using a planned sampling. Herds (n = 434) and cows aged ≥24 months (n = 1891) were randomly selected, and serum samples were tested with the immunofluorescence antibody test (IFAT) using as cut-off point the antibody titer 200. Herd-level and animal-level seroprevalences were 17.8% (95% CI = 14.3%-21.8%) and 18.1% (95% CI = 14.7%-22.1%), respectively. The factors associated with N. caninum infection were farm located in the Sertão mesoregion (Prevalence ratio [PR] = 2.37), mixed production (PR = 1.64), herd size of 34-111 animals (PR = 3.50) and herd size >111 animals (PR = 6.14). The results indicate high N. caninum circulation in the bovine population of the state of Paraíba, semiarid of Brazil, mainly in the Sertão mesoregion, where the highest apparent herd and animal-level prevalences of positive herds were identified. Control strategies should be adopted to mitigate the impact of disease on cattle production, as well as it's suggested the encouragement of conducting surveys in wildlife from Caatinga biome, mainly canids, to provide information on the importance of these animals on the epidemiology of bovine neosporosis.

Global Seropositivity of Swine Leptospirosis: Systematic Review and Meta-Analysis.

Leptospirosis is a major threat to public health worldwide; however, there is no study focused on global seropositivity in pigs. In this study, we grouped publications and performed a systematic review with meta-analysis to gather data related to swine leptospirosis seropositivity published globally. The search method initially used returned a total of 1183 results, of which 20 met all predefined criteria and were therefore included in this review. Meta-analysis with general data was performed and a combined seropositivity of 21.95% was found. Seropositivity was 36.40% in South America, 34.05% in North America, 22.18% in Africa, 17.40% in Oceania, 13.30% in Europe and 13.36% in Asia. The results suggest that there is high seropositivity for leptospirosis in pigs worldwide. Information compiled from this research is relevant to understanding the spread of leptospirosis globally. It is expected that these indicators will contribute to a better understanding of the epidemiology of the disease with a focus on its control and, consequently, on the reduction of cases in the human and animal population.

Bovine Leptospirosis in Caatinga Biome, Brazil: New Insights into Diagnosis and Epidemiology.

Bovine leptospirosis causes economic losses and raises public health concerns. It is possible that there are peculiarities in the epidemiology of leptospirosis in regions with a semiarid climate, such as the Caatinga biome in Brazil, where the climate is hot and dry, and the etiological agent require alternative routes of transmission. This study aimed to close knowledge gaps to the diagnosis and epidemiology of Leptospira spp. infection in cows from the Caatinga biome, Brazil. Samples of the blood, urinary tract (urine, bladder and kidney) and reproductive tract (vaginal fluid, uterus, uterine tube, ovary and placenta) were collected from 42 slaughtered cows. Diagnostic tests included were the microscopic agglutination test (MAT), polymerase chain reaction (PCR) and bacterial isolation. Anti-Leptospira spp. antibodies were found in 27 (64.3%) of the animals analyzed using MAT at a 1:50 dilution (cut-off 50), while 31 (73.8%) animals had at least one organ/fluid where the presence of Leptospira spp. DNA was identified, and 29 animals (69%) were positive at bacteriological culture. The highest sensitivity values for MAT were obtained at the cut-off point of 50. In conclusion, even under hot and dry climate conditions, it is possible that Leptospira spp. can spread through alternative routes such as venereal transmission; moreover, a cut-off of 50 is recommended for the serological diagnosis of cattle from the Caatinga biome.

Impact of Immune-Related Adverse Events on Immune Checkpoint Inhibitors Treated Cancer Patients' Survival: Single Center Experience and Literature Review.

Immune-related adverse events have emerged as a new challenge and its correlation with survival remains unclear. The goal of our study was to investigate the effect of irAE on survival outcomes in solid tumor patients receiving ICI treatment. This was a retrospective, single-center study at a university hospital involving patients with malignancy who received immune checkpoint inhibitors. Chart review was performed on each patient, noting any irAE, including new events or worsening of previous autoimmune condition after starting treatment with ICI. A total of 155 patients were included, 118 (76.1%) were male, with median age of 64 years. Median follow up time was 36 months. Seventy patients (45.2%) had at least one irAE. Of all irAE, nine (8.1%) were classified as grade 3 or higher according to the CTCAE version 5.0. There was one death secondary to pneumonitis. Median ICI cycles until first irAE onset was 4 (range: 2-99). The objective response rate was higher for patients who developed irAE (18.7% vs. 9.0%; p = 0.001), as was median overall survival (18 months (95% CI, 8.67-27.32) vs. 10 (95% CI, 3.48-16.52) months; p < 0.016) and progression free survival (10 months (95% CI, 5.44-14.56) vs. 3 months (95% CI, 1.94-4.05); p = 0.000). The risk of death in patients with irAE was 33% lower when compared to patients without such events (hazard ratio (HR): 0.67; 95% CI, 0.46-0.99; p = 0.043). Development of irAE predicted better outcomes, including OS in patients with advanced solid tumors treated with ICI. Further prospective studies are needed to explore and validate this prognostic value.

Clinical, histopathological, and molecular findings for Mycobacterium avium subspecies paratuberculosis (MAP) in dairy goats under semiarid conditions.

The objective of this study was to report the occurrence of Mycobacterium avium subspecies paratuberculosis (MAP) in dairy goats, via description of their clinical presentation, histopathological findings, and molecular identification of the infectious agent. Screening was performed using IS900 real-time PCR (qPCR) in milk samples from 179 properties in the semiarid of Northeast region of Brazil. Pooled milk samples from all lactating goats from processing plants were submitted to molecular diagnosis. One property had a positive result at qPCR. The production unit which had the positive sample for MAP was located, and an on-site visit to this property was performed to collect individual milk samples, seven of which tested MAP positive by IS900 qPCR. With permission from the owner, two goats (Animal 1 was positive and Animal 2 was negative on first qPCR for MAP) were acquired and euthanized. Animals 1 and 2 had milk and portions of the duodenum, ileum, colon, and mesenteric lymph nodes positive at qPCR for MAP. Animal 1 also had MAP DNA detected in part of the jejunum and cecum. In animal 2, the ileocecal valve tested positive. MAP was not detected in the blood or feces of either animal; however; it was confirmed for the association of clinical findings, histopathology, and qPCR. The gene IS900 from the positive samples were sequenced and showed a 99% similarity with MAP. The MAP was identified for the first time in the goat milk and tissues in the semiarid region of Northeast Brazil.

Molecular detection of Trypanosoma cruzi in equids in a semiarid zone of Pernambuco - Brazil.

Trypanosoma cruzi is the etiological agent of Chagas disease, a neglected and frequently occurring zoonosis in Central and South American countries. Wild mammals and domestic dogs are the main reservoirs of the parasite in the wild and domestic cycles, respectively. The vectors have a wide variety of food sources that can influence transmission cycles. The aim of this study was to determine the prevalence of T. cruzi infection in donkeys (Equus asininos) and mules (Equus mulus) living in rural areas of the Brazilian semi-arid region. Whole-blood samples from 72 equids (65 donkeys and 7 mules) were analyzed by nested polymerase chain reaction (nested PCR). A total of 51.39% of the samples (37/72) were positive. Phylogenetic analysis identified discrete typing units TcI and TcII, which suggested the possibility that donkeys and mules might be participating in domestic/peridomestic and wild transmission cycles. This was the first report of T. cruzi infection in donkeys and mules in Brazil, with high prevalence of positive animals. This places these animals as potential reservoirs for the parasite and the particular features of these hosts, the presence of vectors and the socioeconomic characteristics of the population under semiarid conditions create interactions that may favor transmission and overlapping T. cruzi infection cycles.

Factors associated with small ruminant lentivirus infection in goat herds from Pernambuco state, Northeast region of Brazil.

Serum samples (n = 1532) were collected between May 2011 to April 2012 from goats from 76 herds (49 from dairy farms and 27 herds for genetic improvement) from three geographical regions from the state of Pernambuco, Brazil: Zona da Mata, Agreste, and Sertão. Samples were processed using agar gel immunodiffusion test, with p28 CAEV antigen. The objective was to determine the risk factors for small ruminant lentivirus (SRLV) in dairy goats and goats with high genetic value. Overall, seroprevalence was 13.7% (210/1532) [95% CI: 12-15.4%] in animals and 67.1% (51/76) [95% CI: 56.5%- 77.7%] in herds. In dairy farms the seroprevalence was 73.5% (36/49) [95% CI: 61.1%- 85.8%], and in properties with animals of high genetic value it was 55.6% (15/27) [95% CI: 36.8%- 74.3%]. Robust Poisson regression analysis adjusted by the random effect of the herd showed that risk factors were: importing bucks from another Brazilian state (prevalence ratio [PR] = 4.73 [95% CI: 2.05; 10.88]), not isolating sick animals (PR = 3.27 [95% CI: 2.24; 4.76]), and participating in fairs/animal crowding (PR = 1.52 [95% CI: 1.09; 2.11]). Prevalence results show that SRLV is present in caprine herds in the state of Pernambuco and identified risk factors are strongly related to animal transit. Considering the epidemiological situation, the first step for mitigating the consequences of this disease would be controlling animal transit.