Occupational risks associated with chronic kidney disease of non-traditional origin (CKDnt) in Brazil: it is time to dig deeper into a neglected problem / Riscos ocupacionais associados à doença renal crônica de origem não tradicional (DRCnt) no Brasil: é hora de nos aprofundarmos em um problema negligenciado

Abstract In the past decades, an epidemic of chronic kidney disease (CKD) has been associated with environmental and occupational factors (heat stress from high workloads in hot temperatures and exposure to chemicals, such as pesticides and metals), which has been termed CKD of non-traditional origin (CKDnt). This descriptive review aims to present recent evidence about heat stress, pesticides, and metals as possible causes of CKDnt and provide an overview of the related Brazilian regulation, enforcement, and health surveillance strategies. Brazilian workers are commonly exposed to extreme heat conditions and other CKDnt risk factors, including increasing exposure to pesticides and metals. Furthermore, there is a lack of adequate regulation (and enforcement), public policies, and strategies to protect the kidney health of workers, considering the main risk factors. CKDnt is likely to be a significant cause of CKD in Brazil, since CKD's etiology is unknown in many patients and several conditions for its development are present in the country. Further epidemiological studies may be conducted to explore causal associations and estimate the impact of heat, pesticides, and metals on CKDnt in Brazil. Moreover, public policies should prioritize reducing workers´ exposure and promoting their health and safety.

Resumo Nas últimas décadas, uma epidemia de doença renal crônica (DRC) tem sido associada a fatores ambientais e ocupacionais (estresse térmico decorrente de cargas de trabalho elevadas em altas temperaturas e exposição a produtos químicos, como agrotóxicos e metais), denominada DRC de origem não tradicional (DRCnt). Esta revisão descritiva tem como objetivo apresentar evidências recentes sobre estresse térmico, agrotóxicos e metais como possíveis causas de DRCnt e fornecer uma visão geral das estratégias brasileiras de regulamentação, fiscalização e vigilância sanitária relacionadas. Os trabalhadores brasileiros são comumente expostos a condições extremas de calor e outros fatores de risco de DRCnt, incluindo o aumento da exposição a agrotóxicos e metais. Além disso, há uma falta de regulamentação e fiscalização, políticas públicas e estratégias adequadas para proteger a saúde renal dos trabalhadores em relação aos principais fatores de risco. É provável que a DRCnt seja uma causa significativa de DRC no Brasil, uma vez que a etiologia da doença é desconhecida em muitos pacientes e diversas condições para seu desenvolvimento estão presentes no país. Estudos epidemiológicos devem ser realizados para explorar associações causais e estimar o impacto do calor, dos agrotóxicos e dos metais na DRCnt no Brasil. Além disso, as políticas públicas devem priorizar a redução da exposição dos trabalhadores e a promoção de sua saúde e segurança.

Custo-Efetividade da Oxigenação por Membrana Extracorpórea Venoarterial no Choque Cardiogênico Refratário: Um Estudo na Perspectiva Brasileira / Cost-Utility of Venoarterial Extracorporeal Membrane Oxygenation in Refractory Cardiogenic Shock: A Brazilian Perspective Study

Resumo Fundamento O choque cardiogênico (CC) refratário está associado com altas taxas de mortalidade, e o uso de oxigenação por membrana extracorpórea venoarterial (VA-ECMO, do inglês venoarterial extracorporeal membrane oxygenation) como uma opção terapêutica tem gerado discussões. Nesse sentido, sua custo-efetividade, principalmente em países de baixa e média renda como o Brasil, continua incerto.Objetivos: Conduzir uma análise de custo-efetividade na perspectiva do Sistema Único de Saúde (SUS) para avaliar a custo-efetividade de VA-ECMO combinado com o tratamento padrão em comparação ao tratamento padrão isolado em pacientes adultos com CC refratário. Métodos Acompanhamos uma coorte de pacientes com CC refratário tratados com VA-ECMO em centros de assistência terciária do sul brasileiro. Coletamos dados de desfechos e custos hospitalares. Realizamos uma revisão sistemática para complementar nossos dados e usamos o modelo de Markov para estimar a razão de custo-efetividade incremental (RCEI) por ano de vida ajustado pela qualidade (QALY) e por ano de vida ganho. Resultados Na análise do caso-base, a VA-ECMO gerou uma RCEI de Int$ 37 491 por QALY. Análises de sensibilidade identificaram o custo de internação, o risco relativo de sobrevida, e a sobrevida do grupo submetido à VA-ECMO como principais variáveis influenciando os resultados. A análise de sensibilidade probabilística mostrou um benefício do uso de VA-ECMO, com uma probabilidade de 78% de custo-efetividade no limiar recomendado de disposição a pagar. Conclusões Nosso estudo sugere que, dentro do SUS, VA-ECMO pode ser uma terapia custo-efetiva para o CC refratário. Contudo, a escassez de dados sobre a eficácia e de ensaios clínicos recentes que abordem seus benefícios em subgrupos específicos de pacientes destaca a necessidade de mais pesquisas. Ensaios clínicos rigorosos, incluindo perfis diversos de pacientes, são essenciais para confirmar a custo-efetividade com uso de VA-ECMO e assegurar acesso igualitário a intervenções médicas avançadas dentro dos sistemas de saúde, especialmente em países com desigualdades socioeconômicas como o Brasil.

Abstract Background Refractory cardiogenic shock (CS) is associated with high mortality rates, and the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) as a therapeutic option has generated discussions. Therefore, its cost-effectiveness, especially in low- and middle-income countries like Brazil, remains uncertain.Objectives: To conduct a cost-utility analysis from the Brazilian Unified Health System perspective to assess the cost-effectiveness of VA-ECMO combined with standard care compared to standard care alone in adult refractory CS patients. Methods We followed a cohort of refractory CS patients treated with VA-ECMO in tertiary care centers located in Southern Brazilian. We collected data on hospital outcomes and costs. We conducted a systematic review to supplement our data and utilized a Markov model to estimate incremental cost-effectiveness ratios (ICERs) per quality-adjusted life year (QALY) and per life-year gained. Results In the base-case analysis, VA-ECMO yielded an ICER of Int$ 37,491 per QALY. Sensitivity analyses identified hospitalization cost, relative risk of survival, and VA-ECMO group survival as key drivers of results. Probabilistic sensitivity analysis favored VA-ECMO, with a 78% probability of cost-effectiveness at the recommended willingness-to-pay threshold. Conclusions Our study suggests that, within the Brazilian Health System framework, VA-ECMO may be a cost-effective therapy for refractory CS. However, limited efficacy data and recent trials questioning its benefit in specific patient subsets highlight the need for further research. Rigorous clinical trials, encompassing diverse patient profiles, are essential to confirm cost-effectiveness and ensure equitable access to advanced medical interventions within healthcare systems, particularly in socio-economically diverse countries like Brazil.

Liposarcoma gigante mediastinal. Cirugía radical con abordaje Clamshell y manejo en la Unidad de Cuidados Críticos / Giant Mediastinal Liposarcoma. Radical Surgery with Clamshell Approach and Management in Critical Care Unit

Se presenta a un paciente con liposarcoma mediastinal gigante con dolor torácico, disnea, cuyos estudios por imágenes revelaban la presencia de una gran tumoración de 42 cm en su diámetro mayor que abarcaba todo el mediastino, comprometía ambas cavidades torácicas, rechazaba los pulmones, corazón y grandes vasos. La biopsia con aguja cortante bajo guía ecográfica fue informada como liposarcoma. El paciente tuvo resección completa del tumor mediante la incisión Clamshell. En el post operatorio inmediato, presentó shock circulatorio más disfunción multiorgánica (DOMS): plaquetopenia, insuficiencia renal aguda con necesidad de soporte dialítico, injuria hepática. El soporte y monitoreo especializado en la Unidad de Cuidados Intensivos (UCI) permitió mejoría clínica y buena evolución. Salió de alta en buenas condiciones.

We present a patient with giant mediastinal liposarcoma with chest pain, dyspnea, whose imaging studies revealed the presence of a large tumor measuring 42 cm in its greatest diameter that covered the entire mediastinum, involved both thoracic cavities, rejected the lungs, heart and big glasses. The sharp needle biopsy under ultrasound guidance was reported as liposarcoma. The patient had complete resection of the tumor through the Clamshell incision. In the immediate postoperative period, he presented circulatory shock plus multiple organ dysfunction (DOMS): plateletopenia, acute renal failure with the need for dialytic support, liver injury. Specialized support and monitoring in the Intensive Care Unit (ICU) allowed clinical improvement and good evolution. He was discharged in good condition.

Skin care for toxic shock syndrome: case report / Cuidados com a pele na síndrome do choque tóxico: relato de caso / Cuidado de la piel en el síndrome de shock tóxico: reporte de caso

Objetivo: A síndrome do choque tóxico (SCT) é uma condição multissistêmica grave, causada por Staphylococcus aureus ou Streptococcus pyogenes,e o manejo inicial e contínuo das lesões de pele é essencial para o controle da infecção. Este relato teve o objetivo de descrever os cuidados com a pele nessa síndrome. Relato do caso: Paciente do sexo masculino com abscesso no quadril que evoluiu com febre e hipotensão e consequente transferência para a Unidade de Terapia Intensiva (UTI). Foi diagnosticado com choque séptico de provável foco no quadril, imediatamente abordado cirurgicamente para tratamento local da infecção. Apresentou insuficiência renal, além de disfunção multissistêmica (hepática e cardíaca), instabilidade hemodinâmnica e lesões disseminadas de pele. Com o isolamento do Staphylococcus aureus, iniciou-se clindamicina e o diagnóstico foi de SCT, uma vez que apresentou lesões epidermolíticas desde o início do quadro. Foram iniciadas medidas de recuperação cutânea com a sulfadiazina de prata e, posteriormente, com hidrofibra com prata com restauração do epitélio em 8 dias. Após 10 dias da pele restaurada, o paciente recebeu alta da UTI para enfermaria com manutenção do tratamento proposto. Conclusão: Neste caso, o uso da hidrofibra obteve uma performancesatisfatória, contudo ainda há necessidade de estudos robustos que comprovem tal eficácia. (AU)

Objective: Toxic shock syndrome (TSS) is a severe multisystemic condition caused by Staphylococcus aureus or Streptococcus pyogenes, and initial management of skin lesions is essential for infection control. This article aimed to describe skin care for TSS. Case report: We report a man with a hip abscess who developed fever and hypotension and was subsequently transferred to an intensive care unit (ICU). He was diagnosed with septic shock, probably of hip origin, and was immediately treated surgically for local infection control. He presented with renal failure besides multiple organ dysfunction (hepatic and cardiac), hemodynamic instability, and disseminated skin lesions. With the isolation of Staphylococcus aureus, clindamycin was initiated, and the diagnosis was TSS due to epidermolytic lesions since the onset of the condition. Cutaneous recovery measures were initiated with silver sulfadiazine, followed by silver hydrofiber with skin recovery in 8 days. After 10 days of skin recovery, the patient was discharged from the ICU to the ward with maintenance of the proposed treatment. Conclusion: In this case, the use of hydrofiber showed satisfactory performance; however, robust studies are needed to confirm such efficacy. (AU)

Objetivo: El síndrome de shock tóxico (SST) es una afección multisistémica grave causada por Staphylococcus aureuso Streptococcus pyogenes, y el tratamiento inicial y continuo de las lesiones cutáneas es esencial para controlar la infección. Este informe tuvo como objetivo describir los cuidado de la piel en este síndrome. Reporte del caso:Paciente masculino con absceso en la cadera que desarrolló fiebre e hipotensión y fue tranferido a la Unidad de Cuidados Intensivos (UCI). Se diagnosticó shock séptico, probablemente focalizado en la cadera, por lo que fue inmediatamente abordado quirúrgicamente para tratamiento local de la infección. Presentó insuficiencia renal además de disfunción multisistémica (hepática y cardiaca), inestabilidad hemodinámica y lesiones cutáneas diseminadas. Con el aislamiento de Staphylococcus aureus, se inició clindamicina y el diagnóstico fue SST, ya que presentaba lesiones epidermolíticas desde el inicio del cuadro. Se iniciaron medidas de recuperación cutánea con sulfadiazina de plata y, posteriormente, se optó por hidrofibra con plata, con restauración del epitelio en 8 días. Después de 10 días de piel restaurada, el paciente fue dado de alta de la UCI a planta con mantenimiento del tratamiento propuesto. Conclusión: Alcen este caso, el uso de hidrofibra obtuvo un desempeño satisfactorio, sin embargo, aún se necesitan estudios robustos para probar tal eficacia. (AU)

Shock séptico: complicación atípica de duplicación del tracto alimentario / Septic shock: an atypical complication of alimentary tract duplication

Las duplicaciones del tracto alimentario son un conjunto heterogéneo de anomalías congénitas del tubo digestivo. Su forma de presentación es variada, y pueden desarrollar distintas complicaciones libradas a su evolución natural. La infección es una complicación poco frecuente, pero que no puede desconocerse por la gravedad que implica. Se presenta el caso de una paciente de 2 años de edad, previamente sana, con una complicación atípica de una duplicación del tracto alimentario: un shock séptico. Consultó inicialmente por distensión y dolor abdominal asociado a una masa abdominal palpable. Los estudios imagenológicos evidenciaron una formación líquida parcialmente tabicada en el hemiabdomen derecho. Durante la internación, se presentó una infección intratumoral, que evolucionó al shock séptico. Respondió favorablemente al tratamiento médico del shock, y se realizó la exéresis quirúrgica posteriormente. La anatomía patológica confirmó la duplicación del tracto alimentario.

Alimentary tract duplications are heterogenous congenital anomalies of the digestive tract. Their form of presentation is varied, and they may lead to different complications, depending on their natural course. Infection is a rare complication, but it cannot be ignored because of its severity. Here we describe the case of an otherwise healthy 2-year-old girl with an atypical complication of alimentary tract duplication: septic shock. She initially consulted due to abdominal distension and pain associated with a palpable abdominal mass. The imaging studies showed a partial fluid septation in the right side of the abdomen. During hospitalization, an intratumoral infection developed, which progressed to septic shock. The patient responded favorably to medical treatment for shock, and surgical resection was subsequently performed. The pathology report confirmed the presence of alimentary tract duplication.

Significado biológico y utilidad clínica del lactato en la sepsis / Biological significance and clinical utility of lactate in sepsis

La sepsis es un problema global de salud y la progresión hacia el shock séptico se asocia con un incremento marcado de la morbimortalidad. En este escenario, el aumento del lactato plasmático demostró ser un indicador de gravedad y un predictor de mortalidad, y suele interpretarse casi exclusivamente como marcador de baja perfusión tisular. Sin embargo, últimamente se produjo un cambio de paradigma en la exégesis del metabolismo y propiedades biológicas del lactato. En efecto, la adaptación metabólica al estrés, aun con adecuado aporte de oxígeno, puede justificar la elevación del lactato circulante. Asimismo, otras consecuencias fisiopatológicas de la sepsis, como la disfunción mitocondrial, se asocian con el desarrollo de hiperlactatemia sin que necesariamente se acompañen de baja perfusión tisular. Interpretar el origen y la función del lactato puede resultar de suma utilidad clínica en la sepsis, especialmente cuando sus niveles circulantes fundamentan las medidas de reanimación.

Sepsis is a global health problem; progression to septic shock is associated with a marked increase in morbidity and mortality. In this setting, increased plasma lactate levels demonstrated to be an indicator of severity and a predictor of mortality, and are usually interpreted almost exclusively as a marker of low tissue perfusion. However, a recent paradigm shift has occurred in the exegesis of lactate metabolism and its biological properties. Indeed, metabolic adaptation to stress, even with an adequate oxygen supply, may account for high circulating lactate levels. Likewise, other pathophysiological consequences of sepsis, such as mitochondrial dysfunction, are associated with the development of hyperlactatemia, which is not necessarily accompanied by low tissue perfusion. Interpreting the origin and function of lactate may be of great clinical utility in sepsis, especially when circulating lactate levels are the basis for resuscitative measures.

Desfechos Hospitalares do Infarto do Miocárdio com Supradesnivelamento do Segmento ST em Pacientes Positivos para COVID-19 que Passaram por Intervenção Percutânea Primária / In-Hospital Outcomes of ST-Segment Elevation Myocardial Infarction in COVID-19 Positive Patients Undergoing Primary Percutaneous Intervention

Resumo Fundamento A infecção concomitante por coronavírus 2019 (COVID-19) e o infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST) estão associados ao aumento de desfechos adversos hospitalares. Objetivos O estudo teve como objetivo avaliar as diferenças angiográficas, de procedimentos, laboratoriais e prognósticas em pacientes positivos e negativos para COVID-19 com IAMCSST submetidos à intervenção coronária percutânea primária (ICP). Métodos Realizamos um estudo observacional retrospectivo e unicêntrico entre novembro de 2020 e agosto de 2022 em um hospital de nível terciário. De acordo com o seu estado, os pacientes foram divididos em dois grupos (positivo ou negativo para COVID-19). Todos os pacientes foram internados por IAMCSST confirmado e foram tratados com ICP primária. Os desfechos hospitalares e angiográficos foram comparados entre os dois grupos. P-valores bilaterais <0,05 foram aceitos como estatisticamente significativos. Resultados Dos 494 pacientes com IAMCSST inscritos nesse estudo, 42 foram identificados como positivos para COVID-19 (8,5%) e 452, como negativos. Os pacientes que testaram positivos para COVID-19 tiveram um tempo isquêmico total maior do que os pacientes que testaram negativos para COVID-19 (p = 0,006). Além disso, esses pacientes apresetaram um aumento na trombose de stent (7,1% vs. 1,7%, p = 0,002), no tempo de internação (4 dias vs. 3 dias, p = 0,018), no choque cardiogênico (14,2% vs. 5,5%, p = 0,023) e na mortalidade hospitalar total e cardíaca (p <0,001 e p = 0,032, respectivamente). Conclusões Pacientes com IAMCSST com infecções concomitantes por COVID-19 foram associados ao aumento de eventos cardíacos adversos maiores. Mais estudos são necessários para compreender os mecanismos exatos dos desfechos adversos nesses pacientes.

Abstract Background Concomitant coronavirus 2019 (COVID-19) infection and ST-segment elevation myocardial infarction (STEMI) are associated with increased adverse in-hospital outcomes. Objectives This study aimded to evaluate the angiographic, procedural, laboratory, and prognostic differences in COVID-19-positive and negative patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Methods A single-center, retrospective, observational study was conducted between November 2020 and August 2022 in a tertiary-level hospital. According to their status, patients were divided into two groups (COVID-19 positive and negative). All patients were admitted due to confirmed STEMI and treated with primary PCI. In-hospital and angiographic outcomes were compared between the two groups. Two-sided p-values < 0.05 were accepted as statistically significant. Results Of the 494 STEMI patients enrolled in this study, 42 were identified as having a positive dagnosis for COVID-19 (8.5%), while 452 were negative. The patients who tested positive for COVID-19 had a longer total ischemic time than did those who tested negative for COVID-19 (p=0.006). Moreover, these patients presented an increase in stent thrombosis (7.1% vs. 1.7%, p=0.002), length of hospitalization (4 days vs. 3 days, p= 0.018), cardiogenic shock (14.2% vs. 5.5 %, p= 0.023), and in-hospital total and cardiac mortality (p<0.001 and p=0.032, respectively). Conclusions Patients with STEMI with concomitant COVID-19 infections were associated with increased major adverse cardiac events. Further studies are needed to understand the exact mechanisms of adverse outcomes in these patients.

Uso de la tomografía corporal total en pacientes con heridas de arma de fuego y hemodinámicamente inestables: ¿Rompiendo paradigmas de atención inicial? / Whole-body computed tomography in hemodynamically unstable patients with gunshot wounds: A paradigm shift in trauma management?

Introducción. El objetivo del estudio fue analizar el impacto del uso de la tomografía corporal total en la evaluación de los pacientes con trauma penetrante por proyectil de arma de fuego y hemodinámicamente inestables atendidos en un centro de referencia de trauma. Métodos. Se realizó un estudio analítico, retrospectivo, con base en un subanálisis del registro de la Sociedad Panamericana de Trauma ­ Fundación Valle del Lili. Se incluyeron los pacientes con trauma penetrante por proyectil de arma de fuego atendidos entre 2018 y 2021. Se excluyeron los pacientes con trauma craneoencefálico severo, trauma leve y en condición in extremis. Resultados. Doscientos pacientes cumplieron los criterios de elegibilidad, 115 fueron estudiados con tomografía corporal total y se compararon con 85 controles. La mortalidad intrahospitalaria en el grupo de tomografía fue de 4/115 (3,5 %) vs 10/85 (12 %) en el grupo control. En el análisis multivariado se identificó que la tomografía no tenía asociación significativa con la mortalidad (aOR=0,46; IC95% 0,10-1,94). El grupo de tomografía tuvo una reducción relativa del 39 % en la frecuencia de cirugías mayores, con un efecto asociado en la disminución de la necesidad de cirugía (aOR=0,47; IC95% 0,22-0,98). Conclusiones. La tomografía corporal total fue empleada en el abordaje inicial de los pacientes con trauma penetrante por proyectil de arma de fuego y hemodinámicamente inestables. Su uso no se asoció con una mayor mortalidad, pero sí con una menor frecuencia de cirugías mayores.

Introduction. This study aims to assess the impact of whole-body computed tomography (WBCT) in the evaluation of patients with penetrating gunshot wounds (GSW) who are hemodynamically unstable and treated at a trauma referral center. Methods. An analytical, retrospective study was conducted based on a subanalysis of the Panamerican Trauma Society-FVL registry. Patients with GSW treated between 2018 and 2021 were included. Patients with severe cranioencephalic trauma, minor trauma, and those in extremis were excluded. Patients with and without WBCT were compared. The primary outcome was in-hospital mortality, and the secondary outcome was the frequency of major surgeries (thoracotomy, sternotomy, cervicotomy, and/or laparotomy) during initial care. Results. Two hundred eligible patients were included, with 115 undergoing WBCT and compared to 85 controls. In-hospital mortality in the WBCT group was 4/115 (3.5%) compared to 10/85 (12%) in the control group. Multivariate analysis showed that WBCT was not significantly associated to mortality (aOR: 0.46; 95% CI 0.10-1.94). The WBCT group had a relative reduction of 39% in the frequency of major surgeries, with an associated effect on reducing the need for surgery (aOR: 0.47; 95% CI 0.22-0.98). Conclusions. Whole-body computed tomography was employed in the initial management of patients with penetrating firearm projectile injuries and hemodynamic instability. The use of WBCT was not associated with mortality but rather with a reduction in the frequency of major surgery.

Insuficiencia cardíaca secundaria a mordedura de serpiente. La visión del intensivista: Reporte de caso / Heart failure secondary to a snake bite. The intensivist's vision: Case Report

RESUMEN Antecedentes: El accidente ofídico es una enfermedad desatendida que afecta a los países tropicales. América Latina es la segunda región después de África, con mayor número de casos a nivel mundial. Su curso clínico incluye lesiones locales hasta afectaciones sistémicas como lesiones renales, hematológicas y neurológicas. Las complicaciones cardiacas son raras, especialmente en pacientes que no tienen factores de riesgo cardiovascular. Hay reportes de infarto agudo de miocardio, pero existe poca información sobre la insuficiencia cardíaca debida a Bothrops spp. Reporte de caso: Presentamos el caso de un hombre de 25 años sin factores de riesgo cardiovascular que fue admitido en la unidad de cuidados intensivos y desarrolló insuficiencia cardíaca con choque cardiogénico y fallo multiorgánico secundario a una mordedura de serpiente. Conclusiones: Aunque el curso clínico característico de un accidente ofídico bothrópico y sus manifestaciones sistémicas están principalmente relacionadas con anomalías de la coagulación, hay complicaciones cardiovasculares dentro de su presentación clínica que, aunque raras, si no se detectan prontamente y no se manejan adecuadamente, están asociadas con alta morbilidad y mortalidad.

ABSTRACT Background: Ophidic accident is a neglected disease that affects tropical countries. Latin America is the second region after Africa, with the most cases worldwide. Local lesions accompany its clinical course up to systemic affectations such as renal, hematological, and neurological lesions. Cardiac complications are rare, especially in patients who do not have cardiovascular risk factors. There are reports of acute myocardial infarction, but there is little information about heart failure due to Bothrops spp. Case report: We present the case of a 25-year-old man without cardiovascular risk factors who was admitted to the intensive care unit and developed heart failure with cardiogenic shock and multi-organ failure secondary to a snake bite. Conclusions: Although the characteristic clinical course of a bothropic ophidian accident and its systemic manifestations are mainly related to coagulation abnormalities, there are cardiovascular complications within its clinical presentation that, although rare, if not detected promptly and not adequately managed, are associated with high morbidity and mortality.

Megacolon tóxico: A propósito de un caso / Toxic Megacolon. Case Report

RESUMEN El megacolon tóxico es una enfermedad mortal, que se presenta, con mayor frecuencia, como una complicación de la inflamación intestinal, infecciones e isquemia intestinal. Se caracteriza por la presencia de diarrea sanguinolenta, distensión abdominal, signos de toxicidad sistémica y, en estudios de imagen, se observa dilatación colónica segmentaria. Para el diagnóstico, según los criterios de Jalan, se tiene en cuenta la dilatación colónica más de 6 cm, tres de los siguientes: fiebre, taquicardia, leucocitosis o anemia, y cualquiera de los siguientes criterios: hipotensión, hipovolemia, trastorno electrolítico y estado mental alterado. En este artículo, se presenta el caso de una paciente mujer que ingresa por cuadro de dolor abdominal y diarrea crónica con estudio de imagen, en la que se visualiza dilatación de todo el marco colónico. Se realizan los estudios correspondientes y se diagnostica megacolon tóxico por colitis ulcerativa, por lo que recibe tratamiento médico con evolución favorable. Es dado de alta y reingresa por shock séptico, se realizan estudios y se identifica infección por Clostridium difficile. Se inicia tratamiento antibiótico, pero presenta evolución desfavorable, lo que ocasionó el fallecimiento de la paciente. El presente caso representa la alta mortalidad de esta enfermedad.

ABSTRACT Toxic megacolon is a fatal disease, most commonly occurring as a complication of inflammatory bowel disease, infections, and intestinal ischemia. It is characterized by the presence of bloody diarrhea, abdominal distension, signs of systemic toxicity, and segmental colonic dilation is observed in imaging studies. For the diagnosis, according to the Jalan criteria, colonic dilation of more than 6 cm is taken into account, three of the following: fever, tachycardia, leukocytosis or anemia, and any of the following criteria: hypotension, hypovolemia, electrolyte disorder and altered mental status. This article presents the case of a female patient who was admitted with abdominal pain and chronic diarrhea with an imaging study showing dilation of the entire colonic framework. The corresponding studies were carried out which indicated that she had a toxic megacolon due to colitis. ulcerative, receives medical treatment with favorable evolution, is discharged and readmitted for septic shock, studies are performed and Clostridium difficile infection is identified, antibiotic treatment is started but the evolution is unfavorable, which caused the death of the patient. The present case represents the high mortality of this disease.

Molecular mechanism of ATF6 regulating the reproduction related gene HSPA1L / 基础医学与临床

Objective To explore the effect of endoplasmic reticulum stress activating transcription factor 6(ATF6)on the expression of reproduction related gene heat shock protein family A member 1 like(HSPA1L)and preliminari-ly clarify its regulatory molecular mechanism.Methods The ATF6 over-expression plasmid was transfected into HEK-293T cells and the over-expression efficiency was verified by RT-qPCR and Western blot.The transcriptome sequen-cing information of testis tissue of male ATF6 knockout mice was used to screen five reproduction related genes down-stream of ATF6.The dual luciferase reporter assay selected the downstream genes with high promoter activity and de-tected the effect of over-expression of ATF6 on the promoter activity of downstream genes.The possible binding sites of ATF6 and downstream gene promoters were predicted by gene-regulation.RT-qPCR and Western blot were used to detect the effect of over-expression of ATF6 on downstream gene expression in HEK-293T cells.Whether ATF6 binds to downstream gene promoters was determined by electrophoretic mobility shift assay(EMSA).Results The expres-sion of ATF6 mRNA(P＜0.001)and protein(P＜0.001 and P＜0.05)in HEK-293T cells was significantly increased after transfection.HSPA1L(P＜0.001 and P＜0.05),a reproductive related gene downstream of ATF6 was screened by transcriptome sequencing and dual luciferase reporter assay.ATF6 promoted the truncated promoter activity of HSPA1L(P＜0.001).After over-expression of ATF6,the expression of HSPA1L was significantly increased(P＜0.001).The differences were statistically significant.ATF6 protein could bind to the aagtcgtcac DNA sequence of HSPA1L promoter.Conclusions ATF6,a key molecule of endoplasmic reticulum stress,regulates the expression of reproduction related gene HSPA1L by binding to the promoter of HSPA1L.This result will lay a foundation for further research on the prevention or treatment of endoplasmic reticulum stress(ERS)related male infertility.

C-X3-C motif chemokine ligand 1/C-X3-C motif chemokine receptor 1 pathway in the recovery of memory function in hemorrhagic shock/resuscitation rats / 解剖学报

Objective To investigate the effect of microglia activation regulated by C-X3-C motif chemokine ligand 1(CX3CL1)-C-X3-C motif chemokine receptor 1(CX3CR1)pathway on memory function in hemorrhagic shock/resuscitation rats.Methods The experiment was divided into two parts.In the first part,the rats were randomly divided into sham group,model-0.5 hour group,model-1.5 hour group,model-3 hour group,10 rats in each group.There were differences in the time of hemorrhagic shock among each group.In the second part,rats were randomly divided into control group and CX3CL1 group,10 rats in each group.The rats in CX3CL1 group were treated with CX3CL1 protein factor(intraventricular injection),and the rats in control group were treated with saline.All rats were trained in Morris water maze experiments before model construction,and tests of Morris water maze experiments were carried out after 4 days of model construction.After completion,the whole brains were taken for HE staining and immunohistochemical staining.Cerebrospinal fluid was taken for detection of inflammatory cytokines,and hippocampus tissues were taken for Real-time PCR detection and Western blotting detection.Results Compared with the sham group,the escape latency of rats in model group increased,the number of platform crossings and the resident time in the third quadrant decreased.The neuronal state was impaired in HE staining in model group.In addition,compared with the sham group,the expression of ionized calcium binding adaptor molecule-1(Iba1)in the brain of the rats in model group increased,the contents of tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 in the cerebrospinal fluid increased,and the M1-type microglia markers CD16,TNF-α,IL-1β and inducible nitric oxide synthase(iNOS)mRNA content increased.At the same time,compared with the sham group,the expressions of CX3CL1 and CX3CR1 in the brain of model group decreased,and the expressions of phosphorylated nuclear factor-κB(p-NF-κB)and nucleotide binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)increased.However,compared with the control group,rats in CX3CL1 group had reduced escape latency,increased platform crossing times and quadrantⅢresident time,and recovered neuronal states.In addition,the expression of Iba1 in the brain of CX3CL1 group decreased,the contents of TNF-α and IL-6 in the cerebrospinal fluid decreased,the mRNA contents of M1-type microglia markers like CD16,TNF-α,IL-1β and iNOS decreased,and the mRNA contents of markers of M2-type microglia glial like CD206,transforming growth factor-β(TGF-β),arginase-1(Arg1),Chitinase 3-like protein 1(Ym 1)increased.Conclusion CX3CL1 can help inhibit the excessive activation of microglia,induce the polarization of microglia to M2 type,inhibit the polarization of M1 type,reduce the release of inflammatory cytokines,and alleviate the memory function damage induced by hemorrhagic shock/resuscitation.

Analysis of clinical characteristics and risk factors of shock in patients with acute dichlorvos poisoning / 中华急诊医学杂志

Objective:The aim of this study was to investigate the clinical characteristics and analyze the risk factors of patients with acute dichlorvos poisoning combined with shock.Methods:The clinical data of patients with acute dichlorvos poisoning admitted to the Peking University Third Hospital and the Fifth Medical Center of the PLA General Hospital between January 2019 and September 2020 were retrospectively analyzed, and demographic data, poisoning, clinical manifestations, laboratory tests, therapeutic measures and clinical outcomes were collected to establish a clinical database. The patients were divided into two groups: the shock group and the non-shock group, and the clinical data were compared between the two groups to analyze the clinical characteristics and prognosis of shock in acute dichlorvos poisoning, and the risk factors of shock in acute dichlorvos poisoning were analyzed by logistic regression.Results:A total of 134 patients who met the criteria for acute dichlorvos poisoning were included in this study; the incidence of shock within 24 hours of admission was 39.6% (53/134), and 11 patients (8.21%) died in hospital; the in-hospital morbidity and mortality rate of patients in the shock group was higher than that in the non-shock group (20.8% vs. 0.0%, P<0.001). Symptoms of sphincter relaxation, coma, hypothermia, and organ function damage were more common in the shock group than in the non-shock group; and shock patients had longer hospitalization, ICU stay, and invasive ventilator use. Binary logistic regression analysis showed that the presence of sphincter relaxation manifestations ( OR=10.888, 95% CI: 1.677-70.684, P=0.012) was an independent risk factor for comorbid shock in patients with acute dichlorvos poisoning, and the use of cholinesterase reanimators ( OR=0.246, 95% CI: 0.072-0.846, P=0.026) was a protective factor for combined shock in patients with acute dichlorvos poisoning. Conclusions:The incidence of shock in patients with acute dichlorvos poisoning is high and affects the clinical prognosis, and the presence of sphincter relaxation and the absence of cholinesterase reenergizers are independent risk factors for combined shock in patients with acute dichlorvos poisoning.

An exploratory randomized controlled study on early application of Shenfu injection to prevent septic cardiomyopathy / 中华急诊医学杂志

Objective:To observe the clinical effect of Shenfu injection in preventing septic cardiomyopathy (SIC) in septic patients.Methods:From June 2022 to January 2023, patients with sepsis or septic shock who did not develop SIC were randomly divided into treatment group and control group according to the ratio of 1:1. In the treatment group, Shenfu injection (50 mL) was pumped intravenously once every 12 hours for 5 days. In the control group, 50 mL of normal saline was pumped intravenously once every 12 hours, and the course of treatment was 5 days. The primary end point was the incidence of SIC in the first 5 days. The secondary end points were the application time of vasoactive drugs, fluid balance in the previous week, hospitalization time in ICU, total ventilation time and 28-day mortality.Results:112 patients were randomly divided into two groups. Seven patients in the treatment group were excluded twice, and finally 49 patients were included in the analysis, while six patients in the control group were excluded twice and 50 patients included in the analysis. The total incidence of SIC in the treatment group within 5 days was significantly lower than that in the control group (42.9% vs. 64.0%, P = 0.035). Among them, the left ventricular systolic dysfunction in the treatment group was significantly lower than that in the control group (24.5% vs 52.0%, P=0.005), and there was no significant difference in the incidence of left ventricular diastolic dysfunction between the two groups. The incidence of right ventricular dysfunction in the control group was 28.0%, which was significantly higher than 10.2% in the treatment group ( P = 0.025). The duration of using vasoconstrictors in the treatment group was 75(48, 97) hours, which was significantly lower than 97(66, 28) hours in the control group ( P = 0.039). The duration of inotropic drugs use in the treatment group was 32(18, 49) h, which was also significantly shorter than 44(25, 61) h in the control group ( P=0.046). The fluid balance of the control group in the first week was (1 260±850) mL, which was significantly higher than (450±520) mL in the treatment group ( P=0.008). There was no statistical difference in ICU stay, total ventilation time and 28-day mortality between the two groups (all P > 0.05). Conclusion:Early application of Shenfu injection can significantly reduce the incidence of SIC, accompanied by less use of vasoactive drugs and positive fluid balance, which has a good clinical application prospect.

The value of the ratio of heparin binding protein to albumin in evaluating the state of shock syndrome in Kawasaki disease / 中华急诊医学杂志

Objective:To investigate the value of the ratio of heparin binding protein (HBP) to albumin (ALB) in diagnosis and predict the severity of Kawasaki disease shock syndrome (KDSS).Methods:This study was a retrospective study. Pediatric patients with Kawasaki disease (KD) admitted to the Children's Intensive Care Unit and department of Pediatric Emergency Center of Hunan Children's Hospital from January 2019 to May 2022 were enrolled. The HBP/ALB ratio was calculated according to HBP and serum ALB. The children were divided into three groups (low, medium, and high ratio groups) according to the median and upper and lower quartiles of the HBP/ALB ratio. The differences of each index among the three groups were compared. The receiver operating characteristic curves were drawn to evaluate the clinical value of the HBP/ALB ratio in diagnosis of KDSS and the severity of the disease.Results:A total of 111 cases were included in this study, including 28 cases in the low ratio group, 56 cases in the medium ratio group, and 27 cases in the high ratio group. There were 24 cases with coronary artery damage, 87 cases without coronary artery damage, 27 cases with abnormal ECG findings, and 17 children with KDSS (including 5 cases in the medium ratio group, and 12 cases in the high ratio group). The incidence of KDSS, coronary involvement, and abnormal electrocardiogram proportions in the high ratio group were significantly higher than those in the other two groups. Compared with low and medium ratio groups, the levels of cardiac troponin I, N-terminal pro-brain natriuretic peptide, lactate, stroke output variation, trends in thoracic fluid content, white blood cell count, C-reactive protein, procalcitonin, and D-dimer levels were higher in the high ratio group, while ALB and blood sodium levels were lower in the high ratio group (all P<0.05). There was no significant difference in above indicators between the low and medium ratio groups (all P>0.05). The HBP/ALB ratio had a higher area under the curve, sensitivity, and specificity (0.942, 0.882, and 0.883, respectively) in predicting KDSS compared to HBP alone (0.776, 0.842, and 0.670, respectively). Conclusion:The HBP/ALB ratio could reflect the severity of children with KD and has certain clinical value for prognostic evaluation.

Effect of Shenfu injection on acute lung injury in hemorrhagic shock rats / 临床麻醉学杂志

Objective To observe the effect of Shenfu injection on lung injury caused by hemor-rhagic shock(HS)in rats and explore the related potential mechanism.Methods Thirty-six SPF healthy male SD rats,aged 16-17 weeks,weighing 400-600 g,were randomly divided into three groups:sham op-eration group(group SH),HS group(group HS),and Shenfu injection group(group SF),12 rats in each group.In group SH,only the right femoral vein and femoral artery were separated after anesthesia,and ve-nous catheterization was not performed.HS model was established in groups SF and HS.In group HS,liquid resuscitation was performed through an intravenous catheter,and the resuscitation fluid consisted of the auto-blood lost and the compound sodium chloride injection equivalent to 1.5 times the blood loss and 10 ml/kg normal saline.In group SF,the resuscitation fluid consisted of the lost autoblood and the compound sodium chloride injection equivalent to 1.5 times the blood loss and Shenfu injection 10 ml/kg.The whole perfusion time was about 60 minutes.Six rats in the three groups were randomly anesthetized 24 and 48 hours after op-eration.The wet/dry weight ratio(W/D)of lung tissues was detected.The concentrations of interleukin-6(IL-6),IL-17,IL-10,and transforming growth factor-β(TGF-β)were detected by ELISA,the mRNA ex-pression of retinoic acid-related orphan nuclear receptor γt(RORγt),transcription factor forkhead box pro-tein 3(Foxp3),and hypoxia-inducible factor-1α(HIF-1α)in lung tissues were detected by PCR.The pro-tein contents of RORγt,Foxp3,HIF-1α,aquaporin 1(AQP1),and AQP5 in lung tissue were detected by Western blot.Pathological changesunder HE staining light microscope and lung injury scores were observed.Results Compared with 24 hours after operation,W/D,the concentrations of IL-6 and IL-17,mRNA ex-pression and protein content of RORγt and HIF-1α,and lung injury score were significantly decreased(P＜0.05),the concentrations of IL-10,and TGF-β,Foxp3 mRNA expression and protein content,and AQP1 protein content were significantly increased in group SF 48 hours after operation(P＜0.05).Compared with group SH,W/D,the concentrations of IL-6,IL-17,IL-10,and TGF-β,mRNA expression and protein content of RORγt,Foxp 3,and HIF-1α,and lung injury score were significantly increased(P＜0.05),AQP1 and AQP5 protein contents were significantly decreased in groups HS and SF 24 and 48 hours after operation(P＜0.05),and alveolar structure was damaged under light microscope and alveolar interstitium was filled with a large amount of edematous fluid,during which a large number of inflammatory cells infiltra-ted.Compared with group HS,W/D,the concentrations of IL-6 and IL-17,mRNA expression and protein content of RORγt and HIF-1α,and lung injury score were significantly decreased(P＜0.05),the concen-trations of IL-10 and TGF-β,Foxp3 mRNA expression and protein content,AQP1 and AQP5 protein con-tents were significantly increased in group SF 24 and 48 hours after surgery(P＜0.05),and the alveolar structure was improved under light microscope,and edema was reduced,and the number of inflammatory cells was reduced.Conclusion Shenfu injection can regulate the balance between pro-inflammatory factors IL-6 and IL-17,and anti-inflammatory factors IL-10 and TGF-β,increase the protein content of AQP1 and AQP5 in lung tissue,and decrease the W/D and injury score in lung tissue,thus alleviating lung injury in HS rats.The mechanism may be related to the regulation of HIF-1α-RORγt/Foxp3 balance.

Correlation Analysis between Serum PAD2 Expression Level and APACHE Ⅱ Scores in Patients with Septic Shock / 现代检验医学杂志

Objective To explore the correlation between the expression level of serum peptidylarginine deiminase type 2(PAD2)and acute physiology and chronic health evaluationⅡ(APACHE Ⅱ)scores in patients with septic shock.Methods A total of 103 patients with septic shock admitted to the First People's Hospital of Neijiang from June 2020 to June 22 were regarded as the study group.According to the severity of the condition,the APACHE Ⅱ scores were used to classify study group into mild group(n=39),moderate group(n=51)and severe group(n=13).In addition,103 healthy individuals who underwent physical examination in the hospital during the same period,whose general information matched the study group patients,were selected as the control group.Serum PAD2 expression level in patients with septic shock was determined by enzyme-linked immunosorbent assay.Spearman method was applied to analyze the correlation between serum PAD2 expression level and APACHE Ⅱ scores in patients with septic shock.Logistic regression was applied to analyze the factors affecting the severity of patients with septic shock.The diagnostic value of serum PAD2 in moderate and severe septic shock was evaluated using receiver operating characteristic(ROC)curve analysis.Results The differences in blood creatinine levels(137.52±9.01μmol/L vs 112.22±8.67μmol/L)and platelet counts(74.58±5.19 vs 86.02±5.34)×109/L between study group and control group were statistically significant(t=20.535,15.591,all P<0.05).The expression level of PAD2 in the study group(42.47±6.62 ng/ml)was higher than that in the control group(38.59±5.31 ng/ml),with significant difference(t=4.815,P<0.05).The expression level of serum PAD2 and APACHE Ⅱ scores in patients with septic shock gradually increased with the severity of the condition(F=3.777,176.582,all P<0.05).The expression level of serum PAD2 in patients with septic shock was positively correlated with APACHE Ⅱ scores(r=0.859,P<0.05).Serum creatinine(OR=1.927),PAD2(OR=1.803)and APACHE Ⅱscores(OR=1.657)were risk factors for moderate and severe septic shock(P<0.05),while platelet count(OR=0.781)was a protective factor(P<0.05).The area under the curve(AUC)of serum PAD2 in the diagnosis of moderate and severe septic shock was 0.880,and the sensitivity and specificity were 75.73%(95%CI:0.701～0.826)and 90.29%(95%CI:0.851～0.935),respectively,indicating it had high diagnostic value for moderate and severe septic shock.Conclusion The expression level of serum PAD2 was positively correlated with APACHE Ⅱ scores,and may have a good diagnostic value for moderate and severe septic shock.

Physical factors promote osteogenic differentiation of stem cells / 中国组织工程研究

BACKGROUND:In response to the limitations of traditional repair methods for bone defects,stem cells are widely used in the research of regenerative medicine.Chemical factors are the current research hotspots,but recent studies confirm that the application of physical factors to regulate stem cell differentiation at home and abroad has been intensifying,and physical factors combined with biological scaffolds in bone tissue engineering provide a new idea and method for solving the difficult problem of bone defect repair,with good development prospects. OBJECTIVE:To summarize the molecular mechanisms of physical factors such as electromagnetic fields and ultrasound on osteogenic differentiation of stem cells as well as the regulation of signaling pathways and the feasibility of their application in bone tissue engineering. METHODS:A computerized search of the CNKI and PubMed for the last 20 years was conducted.In the title and abstract,we used"stem cell,bone defect,osteogenic differentiation,electromagnetic fields,ultrasound,shock wave,low-level laser therapy,mechanical force,bone tissue engineering"in Chinese and"stem cell,osteoporosis,osteogenic differentiation,electromagnetic fields,ultrasound,bone tissue engineering"in English as search terms.A total of 94 relevant articles were included for review. RESULTS AND CONCLUSION:(1)As a non-invasive,non-contact adjuvant therapy,physical factors have a significant impact on bone tissue engineering,and have a positive effect on regulating osteogenic differentiation of stem cells,promoting cell proliferation and viability in bone engineering scaffolds.(2)In addition to activating signaling pathways and osteogenic gene transcription,physical factors can also improve vascularization,increase the volume,area and thickness of bone formed in the stent,promote osseointegration,and improve the success rate of bone scaffolds in regenerating healthy bone tissue.(3)However,the use of physical factors for bone tissue engineering uses different experimental conditions,such as scaffold type,cell type,and intervention conditions,and cannot be directly compared to determine the best parameter settings.There is also a lack of consistency in the effectiveness of these different interventions in promoting fracture healing in clinical use.Therefore,it is necessary to further determine the optimal parameters of physical factors for bone tissue engineering in the future.(4)In general,as an ideal adjuvant therapy,physical factors have great potential in combining with various biomaterials and applying them in bone tissue engineering.

Visual analysis of extracorporeal shock wave therapy for pain / 中国组织工程研究

BACKGROUND:Extracorporeal shock wave therapy,as its potential benefits for various musculoskeletal diseases,has received widespread attention.Increasingly studies have demonstrated that it has excellent effects such as pain relief and functional recovery.However,bibliometric analysis in the domain of extracorporeal shock wave therapy for pain is relatively lacking. OBJECTIVE:To visually analyze the studies related to extracorporeal shock wave therapy for pain and to sort out the knowledge structure and explore its research status as well as hot trends in this field at home and abroad. METHODS:The publications related to extracorporeal shock wave therapy for pain from 2002 to 2022 in Web of Science Core Collection database and CNKI database were searched.Visual analysis using Citespace software was performed to produce the diagrams and interpret their meanings. RESULTS AND CONCLUSION:A total of 2 101 studies were included.The number of documents issued showed a fluctuating upward trend and the United States and China had certain advantages in the number of documents issued.The issuing institutions are mainly universities and hospitals and the issuing authors mostly belonged to independent teams.The exchange between issuing institutions and authors needed to be strengthened and the degree of cross-institutional and cross-regional cooperation was low.Keyword visual analysis indicated that extracorporeal shock wave therapy has been widely used in musculoskeletal diseases and further studies should focus on multidisciplinary in-depth study and observation of the clinical efficacy of combined therapy.The studies on the topic of extracorporeal shock wave therapy treating pain mainly focus on musculoskeletal diseases,including plantar fasciitis,scapulohumeral periarthritis,and tennis elbow.In recent years,combined treatment with ultrasound-guided injection therapy,traditional Chinese treatment techniques and expansion of new fields become research trends and hotspots of concern.

Use of vasoactive agents in children with septic shock-similarities and differences with adults / 中国小儿急救医学

As one of the important causes of death in critically ill patients，septic shock has always been the focus of research in the field of critical care medicine.Correct and rational use of vasoactive drug is an important treatment for septic shock.The hemodynamic changes of septic shock in children and adults are different，which lead to the different use of vasoactive drugs.This review summarized the similarities and differences of the application of vasoactive drugs between children and adults with septic shock，thus could provide a reference for clinical practice.