Acidentes por animais ofídicos: repercussões sistêmicas e prognóstico

Introdução: Os acidentes por animais peçonhentos são um problema mundial, principalmente em países com regiões tropicais e subtropicais, com alto índice de morbidade e mortalidade. No Brasil, há quatro tipos de acidentes ofídicos de interesse em saúde: botrópico, crotálico, laquético e elapídico. O acidente botrópico, mais comum no país, é causado por serpentes dos gêneros Bothrops e Bothrocophias. O acidente é causado pelas cascavéis, as quais são identificadas pela presença de chocalho. Já o acidente laquêtico é causado pela surucucu, maior serpente peçonhenta do Brasil. São manifestações clínicas frequentes, de caráter precoce e progressivo a dor e o edema, podendo ocorrer também bolhas e sangramentos no local da picada. Em casos mais graves pode acontecer necrose de tecidos com formação de abscessos e desenvolvimento de síndrome compartimental. Também pode ocorrer náuseas, vômitos, sudorese, hipotensão arterial e, mais raramente, choque, insuficiência renal aguda, septicemia e coagulação intravascular disseminada. O tratamento efetivo utilizado para neutralizar os envenenamentos é a administração de soroterapia específica. Já a terapêutica geral inclui hidratação, mantendo-se o fluxo urinário de 1 a 2 mL/kg/hora na criança e 30 a 40 mL/hora no adulto, com o auxílio, se necessário, de manitol e diuréticos de alça por via intravenosa. Deve-se orientar a vacinação contra tétano, devido ao risco de introdução de esporos da bactéria Clostridium tetani no local da ferida. O presente estudo objetivou avaliar as repercussões sistêmicas dos diferentes tipos de veneno, o manejo adequado e o prognóstico. Metodologia: revisão integrativa da literatura, nas bases de dados Pubmed, e Scielo, com os descritores: “Animais Peçonhentos”, “Mordedura de Serpentes” e “Snake Venoms”. Foram utilizados 11 artigos, com data de publicação entre 2014 e 2021.  Desenvolvimento: As serpentes do grupo botrópico, como a jararaca e a cascavel, são responsáveis pela maioria dos acidentes ofídicos no país. Seus venenos contêm proteases e fosfolipases A2, que causam danos locais significativos, como inflamação, hemorragia, edema, dor e necrose. Além disso, podem ocorrer sintomas sistêmicos, como sangramentos na pele e mucosas, hipotensão e insuficiência renal aguda. O tratamento é realizado com o soro antibotrópico ou soro botrópico-laquético, que neutraliza os efeitos tóxicos do veneno. Os animais do grupo laquético apresentam venenos semelhantes aos botrópicos e manifestações clínicas parecidas. No entanto, sintomas vagais, como náuseas, vômitos e hipotensão, são mais comuns nos acidentes laquéticos, permitindo a diferenciação clínica. O tratamento também é realizado com o soro antibotrópico-laquético. As serpentes cortálicas, como a cascavel, possuem venenos com alta concentração de proteínas de alto peso molecular, como enzimas e peptídeos. Os sintomas locais, como dor, edema e parestesia, são geralmente discretos. No entanto, o veneno é principalmente neurotóxico, causando paralisia por bloqueio da transmissão neuromuscular. Também podem ocorrer efeitos proteolíticos e hemorrágicos. A insuficiência renal é uma complicação grave. O tratamento envolve o uso do soro anticrotálico. As serpentes elapídicas, como a Naja, possuem venenos primariamente neurotóxicos. Eles interferem na transmissão de impulsos nervosos, levando à paralisia, problemas respiratórios e, em casos graves, asfixia. O veneno elapídico também pode ter efeitos cardiotóxicos, causando arritmias e insuficiência cardíaca. Os sintomas locais geralmente são discretos. O tratamento é realizado com o soro antielapídico. É fundamental ressaltar que a gravidade dos acidentes com serpentes pode variar de acordo com a espécie, quantidade de veneno injetado, local da mordida e estado de saúde do indivíduo. O tratamento precoce com soroterapia específica é essencial para neutralizar os efeitos do veneno. Além disso, medidas de suporte, como hidratação adequada e administração de analgésicos, são importantes para o manejo dos pacientes. Conclusão: Em resumo, os acidentes com serpentes no Brasil são um problema de saúde pública que requer uma abordagem multidisciplinar. O diagnóstico e tratamento precoces, com o uso de soros específicos, são essenciais para reduzir complicações e aumentar as chances de recuperação. Além disso, medidas de suporte e a conscientização da população sobre serpentes peçonhentas são importantes para prevenir acidentes. A educação contínua e a promoção de medidas preventivas são fundamentais para reduzir o impacto desses acidentes na saúde pública

NEUROCIÊNCIA E TDAH: EXPLORANDO CONEXÕES CEREBRAIS E AVANÇOS EM INTERVENÇÕES TERAPÊUTICAS

The topic involving neuroscience and attention deficit hyperactivity disorder is complex and multifaceted, in addition to involving the understanding of the neural bases and how each region is affected and interfered, it is also possible to develop better and efficient therapeutic processes from this. that help to significantly improve the quality of life of each individual. Objective: To understand the relationship between neuroscience and ADHD, in addition to addressing the best therapeutic paths. Methodology: The bibliographic search to carry out the integrative review was conducted in specialized databases, PubMed and Scopus, using a combination of controlled and uncontrolled terms related to neuroscience, ADHD and therapeutic interventions, the Mesh used: “Attention Deficit Disorder with Hyperactivity ”; “Cognitive Neuroscience”; “Mental Health”. Results: The multiple neural systems and neurotransmitters affected in this process cause impacts on the nervous system and with this arises the importance of developing therapeutic approaches. Thus, the main points of impact are the prefrontal cortex, dopaminergic system, striatum nucleus and attentional network. Each affected region causes a series of changes confirming the theory that ADHD is a neurobiological condition.A temática envolvendo a neurociência e o Transtorno do déficit de atenção e hiperatividade é complexa e multifacetada, além de envolver o entendimento das bases neurais e como cada região é afetada e interferida, também é possível a partir disso desenvolver melhores e eficientes processos terapêuticos que ajudem na melhora significativa na qualidade de vida de cada indivíduo. Objetivo: Entender a relação entre a neurociência e o TDAH, além de abordar os melhores caminhos terapêuticos. Metodologia: A busca bibliográfica para realização da revisão integrativa foi conduzida em bases de dados especializadas, PubMed e Scopus, utilizando uma combinação de termos controlados e não controlados relacionados à neurociência, TDAH e intervenções terapêuticas, os Mesh usados: “Attention Deficit Disorder with Hyperactivity”; “Neurociencia Cognitiva”; “Mental Health”. Resultados: Os múltiplos sistemas neurais e  neurotransmissores afetados nesse processo causam impactos no sistema nervoso e com isso surge a importância de desenvolvimento de abordagens terapêuticas. Desse modo, os principais pontos de impacto são córtex pré-frontal, sistema dopaminérgico, núcleo estriado e rede atencional. Cada região afetada causa uma série de mudanças confirmando a teoria que o TDAH é uma condição neurobiológica.&nbsp

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting & Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (<60, 60-69, and >_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 & PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages <60, 60-69, and >_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791