Effects of myenteric denervation on extracellular matrix fibers and mast cell distribution in normal stomach and gastric lesions

Abstract\ud \ud \ud \ud Background\ud \ud In this study the effect of myenteric denervation induced by benzalconium chloride (BAC) on distribution of fibrillar components of extracellular matrix (ECM) and inflammatory cells was investigated in gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Rats were divided in four experimental groups: non-denervated (I) and denervated stomach (II) without MNNG treatment; non-denervated (III) and denervated stomachs (IV) treated with MNNG. For histopathological, histochemical and stereological analysis, sections of gastric fragments were stained with Hematoxylin-Eosin, Picrosirius-Hematoxylin, Gomori reticulin, Weigert's Resorcin-Fuchsin, Toluidine Blue and Alcian-Blue/Safranin (AB-SAF).\ud \ud \ud \ud Results\ud \ud BAC denervation causes an increase in the frequency of reticular and elastic fibers in the denervated (group II) compared to the non-denervated stomachs (group I). The treatment of the animals with MNNG induced the development of adenocarcinomas in non-denervated and denervated stomachs (groups III and IV, respectively) with a notable increase in the relative volume of the stroma, the frequency of reticular fibers and the inflammatory infiltrate that was more intense in group IV. An increase in the frequency of elastic fibers was observed in adenocarcinomas of denervated (group IV) compared to the non-denervated stomachs (group III) that showed degradation of these fibers. The development of lesions (groups III and IV) was also associated with an increase in the mast cell population, especially AB and AB-SAF positives, the latter mainly in the denervated group IV.\ud \ud \ud \ud Conclusions\ud \ud The results show a strong association in the morphological alteration of the ECM fibrillar components, the increased density of mast cells and the development of tumors induced by MNNG in the non-denervated rat stomach or denervated by BAC. This suggests that the study of extracellular and intracellular components of tumor microenvironment contributes to understanding of tumor biology by action of myenteric denervation.We are grateful to Domingos Zanchetta Netto and Luiz Roberto Falleiros-Jr for technical assistance. CFE and CBM were supported by Fundação de Amparo á Pesquisa - FAPESP (grants 08/05722-6 and 03/10634-5, respectively) and SRT by Conselho Nacional de Desenvolvimento Cientifico e Tecnológico - CNPq (grants 301111/05-7 and 300163/2008-8).We are grateful to Domingos Zanchetta Netto and Luiz Roberto FalleirosJr for technical assistance. CFE and CBM were supported by Fundação de Amparo á Pesquisa FAPESP (grants 08/057226 and 03/106345, respectively) and SRT by Conselho Nacional de Desenvolvimento Cientifico e Tecnológico CNPq (grants 301111/057 and 300163/20088)

Lemierre’s Syndrome: an atypical co-infection by Staphylococcus aureus and Mycobacterium tuberculosis

Lemierre’s syndrome (LS) stands as a rare and life-threatening condition. It is secondary to an acute oropharyngeal infection, leading to thrombosis of the internal jugular vein (IJV) and subsequent dissemination to other organs through metastatic septic emboli, predominantly affecting the lungs. While anaerobic bacterium such as Fusobacterium necrophorum typically prevail as etiological agents for this syndrome, the presented case illustrates an uncommon occurence of Lemierre’s Syndrome incited by a co-infection of Staphylococcus aureus and Mycobacterium tuberculosis in a 17-year old immunocompetent female. This highlights the importance of identifying alternative etiological agents capable of provoking this severe condition in order to provide tailored and timely therapeutic measures

COVID-19-related multisystem inflammatory syndrome in adult: the first death in Brazil

The precise pathogenesis of COVID-19-related multisystem inflammatory syndrome remains largely elusive, despite its rarity. The syndrome symptoms often overlap with those of other infections, posing challenges for prompt diagnosis. A male patient, 34 years old, was admitted with suspicion of severe dengue, rapidly progressing to multiple organ dysfunction. Dengue tests resulted negative, and he passed away after four days. This case occurred approximately four weeks after the initial onset of COVID-19 and met all diagnostic criteria as defined by the Centers for Disease Control and Prevention. This report presents the first documented case of fatal multisystem inflammatory syndrome in adult (MIS-A) in Brazil. Recognizing the significance of suspecting this syndrome and promptly initiating treatment at an early stage are essential for minimizing damage and mortality

Hematoma hepático volumoso em paciente com Dengue: nova complicação de uma velha doença

Introdução: Em 2022, a dengue apresentou uma taxa de incidência de 667 casos por 100 mil habitantes, chegando a cerca de quase 1,5 milhão de casos no Brasil, mostrando portanto sua grande prevalência. Manifestações não usuais têm sido descritas progressivamente, demonstrando o caráter heterogêneo desta patologia. Neste estudo, é descrito o relato inédito de uma complicação atípica de dengue, a degeneração hemorrágica de possível adenoma hepático prévio associado ainda a derrame pleural. Objetivos: Realizar descrição clínica de complicação incomum e rara de degeneração hemorrágica de grande volume de possível adenoma hepático em um paciente com dengue avaliado em um Centro Hospitalar Terciário. Metodologia: Trata-se de um relato de caso com delineamento descritivo e observacional, sem grupo controle e com caráter narrativo. Relato de caso e discussão: Paciente sexo feminino, 36 anos, branca, ex-tabagista e hipertensa, iniciou há 10 dias da admissão, febre e exantema pruriginoso, evoluindo com dor em hipocôndrio direito e sintomas constitucionais. À admissão, apresentava-se hipotensa com descompressão brusca positiva em abdome e petéquias generalizadas. Exames iniciais demonstraram anemia, plaquetopenia, elevação de enzimas canaliculares e hepáticas e em tomografia computadorizada (TC) de abdome, hematoma subcapsular em lobo hepático direito de 510 cm³. À avaliação da equipe cirúrgica, houve a hipótese de adenoma hepático com degeneração hemorrágica, com proposta conservadora. A paciente evoluiu com piora clínica e queda de nível hematimétrico, com nova TC com aumento do hematoma - 1200 cm³, sendo realizado transfusão de hemoderivados. Após 2 dias, apresentou piora laboratorial, dessaturação com necessidade de intubação orotraqueal e hipotensão com necessidade de droga vasoativa, sendo encaminhada à UTI. Apresentou Hemoculturas com Haemophilus influenzae e sorologia para dengue reagente (Anti-Dengue IgM). Ademais, viu-se em nova TC alterações pulmonares com presença de derrame pleural bilateral, consolidações permeadas por opacidades "vidro fosco" e aumento do hematoma - 1300 cm³. Levantaram-se as hipóteses de Síndrome Respiratória Aguda Grave, lesão pulmonar aguda relacionada à transfusão e sobrecarga circulatória pós-transfusional. Após medidas de suporte, evoluiu com boa resposta. Após alguns dias, paciente cursou com nova piora sendo evidenciado piora do derrame pleural (exsudato) com necessidade de drenagem. A paciente recebeu alta no 47° dia de internação. Em TC realizada pós alta, houve redução hematoma (180 cm³) e raio-X de tórax sem alterações. Conclusão: A dengue tem apresentando manifestações atípicas. Relatou-se um caso de uma complicação até então não encontrada na literatura, com desfecho favorável, a fim de aprimorar o conhecimento científico, de melhorar a assistência médica e de nortear futuros estudos e tratamentos

Understanding the Potential Impact of Different Drug Properties On SARS-CoV-2 Transmission and Disease Burden: A Modelling Analysis

Background The public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods Using a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. Results The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions Advances in the treatment of COVID-19 to date have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority

Understanding the potential impact of different drug properties on SARS-CoV-2 transmission and disease burden : a modelling analysis

Q1Q1Background The unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods and Findings develop a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care to explore the potential public-health impact of a range of different potential therapeutics, under a range of different scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) drug efficacy in the absence of supportive care. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. We find the impact of drugs like dexamethasone (which are delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in highincome countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions There is a global asymmetry in who is likely to benefit from advances in the treatment of COVID-19 to date, which have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priorityRevista Internacional - Indexad

Zika Brazilian Cohorts (ZBC) Consortium: Protocol for an Individual Participant Data Meta-Analysis of Congenital Zika Syndrome after Maternal Exposure during Pregnancy.

Despite great advances in our knowledge of the consequences of Zika virus to human health, many questions remain unanswered, and results are often inconsistent. The small sample size of individual studies has limited inference about the spectrum of congenital Zika manifestations and the prognosis of affected children. The Brazilian Zika Cohorts Consortium addresses these limitations by bringing together and harmonizing epidemiological data from a series of prospective cohort studies of pregnant women with rash and of children with microcephaly and/or other manifestations of congenital Zika. The objective is to estimate the absolute risk of congenital Zika manifestations and to characterize the full spectrum and natural history of the manifestations of congenital Zika in children with and without microcephaly. This protocol describes the assembly of the Consortium and protocol for the Individual Participant Data Meta-analyses (IPD Meta-analyses). The findings will address knowledge gaps and inform public policies related to Zika virus. The large harmonized dataset and joint analyses will facilitate more precise estimates of the absolute risk of congenital Zika manifestations among Zika virus-infected pregnancies and more complete descriptions of its full spectrum, including rare manifestations. It will enable sensitivity analyses using different definitions of exposure and outcomes, and the investigation of the sources of heterogeneity between studies and regions

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children

IntroductionZika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.Methods and analysisWe will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.Ethics and disseminationThe IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.Trial registration numberPROSPERO International prospective register of systematic reviews (CRD42017068915).</jats:sec