Trimethylamine N-oxide and kidney diseases: what do we know? / N-óxido de trimetilamina e doenças renais: o que sabemos?

Abstract In the human gut, there is a metabolically active microbiome whose metabolic products reach various organs and are used in the physiological activities of the body. When dysbiosis of intestinal microbial homeostasis occurs, pathogenic metabolites may increase and one of them is trimethyl amine-N-oxide (TMAO). TMAO is thought to have a role in the pathogenesis of insulin resistance, diabetes, hyperlipidemia, atherosclerotic heart diseases, and cerebrovascular events. TMAO level is also associated with renal inflammation, fibrosis, acute kidney injury, diabetic kidney disease, and chronic kidney disease. In this review, the effect of TMAO on various kidney diseases is discussed.

Resumo No intestino humano, existe um microbioma metabolicamente ativo cujos produtos metabólicos alcançam diversos órgãos e são utilizados nas atividades fisiológicas do corpo. Quando ocorre disbiose da homeostase microbiana intestinal, os metabólitos patogênicos podem aumentar, e um deles é o N-óxido de trimetilamina (TMAO). Acredita-se que o TMAO tenha um papel na patogênese da resistência à insulina, diabetes, hiperlipidemia, doenças cardíacas ateroscleróticas e eventos cerebrovasculares. O nível de TMAO também está associado à inflamação renal, fibrose, lesão renal aguda, doença renal diabética e doença renal crônica. Nesta revisão, discute-se o efeito do TMAO em diversas doenças renais.

Divertículo de Meckel complicado. Experiencia de 15 años en un hospital interzonal / Complicated Meckel's diverticulum. Fifteen years of experiencein an interzonal hospital in the Province of Buenos Aires

Introducción: el divertículo de Meckel es la anomalía congénita más frecuente del tracto gastrointestinal. Puede presentarse con hemorragia, obstrucción intestinal o diverticulitis, complicaciones que disminuyen con la edad, por lo que en el adulto el diagnóstico suele ser incidental. El tratamiento de las complicaciones es quirúrgico, mediante diverticulectomía o resección segmentaria del intestino delgado, dependiendo de sus características morfológicas. Objetivo: analizar nuestra experiencia en el manejo del divertículo de Meckel complicado en un período de 15 años. Diseño: estudio descriptivo, observacional, transversal, retrospectivo. Material y métodos: se revisaron las historias clínicas de los pacientes operados por divertículo de Meckel complicado en el Servicio de Cirugía General del Hospital San Roque durante el periodo 2007-2022. Se registraron datos demográficos, presentación clínica, diagnóstico preoperatorio, tratamiento quirúrgico, complicaciones postoperatorias y hallazgos histopatológicos. Resultados: se incluyeron 25 pacientes, 21 (84%) hombres, 3 menores de 18 años. La presentación clínica fue un síndrome de fosa iliaca derecha en el 80% de los casos, obstrucción intestinal en el 16% y hemorragia en el 4%. En solo 2 casos se realizó el diagnóstico preoperatorio, confirmado mediante tomografía computada. Se realizó diverticulectomía en el 68% de los pacientes y resección segmentaria el 32%. El abordaje fue laparotómico en el 64%, principalmente en el periodo inicial y laparoscópico en el 36%. Hubo una complicación IIIb de Clavien-Dindo en un paciente pediátrico tratado con drenaje percutáneo. En un solo paciente (4%), que se presentó con hemorragia digestiva masiva, se encontró epitelio de tipo gástrico y páncreas ectópico en el divertículo. Conclusiones: En nuestra experiencia el divertículo de Meckel complicado se presentó predominantemente en hombres. La complicación más frecuente en el adulto fue la diverticulitis. El diagnóstico preoperatorio fue infrecuente y realizado por tomografía computada. La diverticulectomía es suficiente en la mayoría de los casos. Actualmente, la laparoscopia es una herramienta segura, rentable y eficiente que permite el diagnóstico y tratamiento oportunos de esta entidad. (AU)

Introduction: Meckel's diverticulum is the most common congenital malformation of the gastrointestinal tract. It can present with bleeding, intesti-nal obstruction or diverticulitis, complications that decrease with age, so in adults the diagnosis is usually incidental. Treatment of complications is surgical, through diverticulectomy or segmental resection of the small intestine, depending on its morphological characteristics. Objective: to analyze our experience in the management of complicated Meckel's diverticulum over a period of 15 years. Design: descriptive, observational, cross-sectional, retrospective study. Materials and methods: the medical records of patients operated on for complicated Meckel's diverticulum in the General Surgery Service of the San Roque Hospital during the period 2007-2022 were reviewed. Demo-graphic data, clinical presentation, preoperative diagnosis, surgical treatment, postoperative complications, and histopathological findings were recorded. Results: twenty-five patients were included, 21 (84%) men, 3 under 18 years of age. The clinical presentation was a right iliac fossa syndrome in 80% of cases, intestinal obstruction in 16% and hemorrhage in 4%. In only 2 cases was the preoperative diagnosis made, confirmed by computed tomography. Diverticulectomy was performed in 68% of patients and segmental resection in 32%. The approach was by laparotomy in 64%, mainly in the initial period, and by laparoscopy in 36%. There was a Clavien-Dindo IIIb complication in a pediatric patient treated with percutaneous drain-age. In only one patient (4%), who presented with massive gastrointestinal bleeding, gastric-type epithelium and ectopic pancreas were found in the diverticulum. Conclusions: In our experience, complicated Meckel's diverticulum occurred predominantly in men. The most frequent complication in adults was diverticulitis. Preoperative diagnosis was infrequent and was made by computed tomography. Diverticulectomy is sufficient in most cases. Currently, laparoscopy is a safe, profitable and efficient tool that allows for the timely diagnosis and treatment of this entity. (AU)

Fístula enterocutánea: un enfoque desde las generalidades y el estado nutricional / Enterocutaneous fistula: An approach based on generalities and nutritional status

Introducción. Una fístula es una conexión anormal entre dos superficies epitelizadas. Cerca del 80 % de las fístulas entero-cutáneas son de origen iatrogénico secundarias a cirugía, y un menor porcentaje se relacionan con traumatismos, malignidad, enfermedad inflamatoria intestinal o isquemia. La morbilidad y las complicaciones asociadas pueden ser significativas, como la desnutrición, en la que intervienen múltiples factores. Métodos. Se realizó una búsqueda de la literatura en las bases de datos de PubMed, Google Scholar y SciELO, utilizando las palabras claves descritas y se seleccionaron los artículos más relevantes de los últimos años. Resultados. La clasificación de las fístulas se basa en su anatomía, su gasto o secreción diaria y su localización. Existe una tríada clásica de las complicaciones: sepsis, desnutrición y anomalías electrolíticas. El control del gasto de la fístula, el drenaje adecuado de las colecciones y la terapia antibiótica son claves en el manejo precoz de estos pacientes. Los estudios recientes hacen hincapié en que la sepsis asociada con la desnutrición son las principales causas de mortalidad. Conclusiones. Esta condición representa una de las complicaciones de más difícil y prolongado tratamiento en cirugía abdominal y colorrectal, y se relaciona con importantes tasas de morbilidad, mortalidad y altos costos para el sistema de salud. Es necesario un tratamiento multidisciplinario basado en la reanimación con líquidos, el control de la sepsis, el soporte nutricional y el cuidado de la herida, entre otros factores.

Introduction. A fistula is an abnormal connection between two epithelialized surfaces. About 80% of enterocutaneous fistulas are of iatrogenic origin secondary to surgery, and a smaller percentage are related to trauma, malignancy, inflammatory bowel disease or ischemia. The associated morbidity and complications can be significant, such as malnutrition, in which multiple factors intervene. Methods. A literature search was carried out in the PubMed, Google Scholar and SciELO databases using the keywords described and the most relevant articles from recent years were selected. Results. The classification of fistulas is based on their anatomy, their daily secretion output, and their location. There is a classic triad of complications: sepsis, malnutrition and electrolyte abnormalities. Control of fistula output, adequate drainage of the collections and antibiotic therapy are key to the early management of these patients. Recent studies emphasize that sepsis associated with malnutrition are the main causes of mortality. Conclusions. This condition represents one of the most difficult and prolonged complications to treat in abdominal and colorectal surgery, and is related to significant rates of morbidity, mortality and high costs for the health system. Multidisciplinary treatment based on fluid resuscitation, sepsis control, nutritional support, and wound care, among other factors, is necessary.

Osificación heterotópica mesentérica como causa de obstrucción intestinal en un paciente con abdomen séptico / Mesenteric Heterotopic Ossification as a Cause of Intestinal Obstruction in a Patient with a Septic Abdomen

Presentación del caso. Se trata de un masculino de 49 años, con historia de un trauma abdominal cerrado con un objeto contuso sin alteraciones hemodinámicas. La ecografía focalizada de traumatismos resultó positiva a líquido libre en la cavidad abdominal en tres ventanas. Intervención terapéutica. Fue sometido a múltiples laparotomías exploratorias con lavados de cavidad abdominal posterior a presentar un cuadro de abdomen séptico Björk 4, quien después de 38 días de estancia intrahospitalaria presentó una fístula enteroatmosférica que causaba un déficit nutricional. En una intervención quirúrgica se realizó el cierre de la fístula enteroatmosférica, con el hallazgo de tejido óseo trabecular en cavidad abdominal, correspondiente a osificación heterotópica intraabdominal de formación reciente. Evolución clínica. Luego de la anastomosis del intestino delgado presentó signos de obstrucción intestinal, a causa de esto, se realizó una nueva laparotomía exploratoria, en la que se encontró tejido óseo adherido al mesenterio del intestino delgado que generó una obstrucción completa, se extirpó el material óseo y se logra restablecer el flujo intestinal liberando la obstrucción en el intestino delgado

Case presentation. A 49-year-old male, with a history of blunt abdominal trauma with a blunt object without hemodynamic alterations. The focused trauma ultrasound was positive for free fluid in the abdominal cavity in three windows. Treatment.The patient underwent multiple exploratory laparotomies with peritoneal lavage after presenting a septic abdomen (Björk 4), who after 38 days of intrahospital stay presented an enteroatmospheric fistula that caused a large nutritional deficit. In a surgical intervention, the enteroatmospheric fistula was closed, with the finding of trabecular bone tissue in the abdominal cavity, corresponding to intra-abdominal heterotopic ossification of recent formation. Outcome. After the small intestine anastomosis, he presented signs of intestinal obstruction, because of this, a new exploratory laparotomy was performed, in which bone tissue was found adhered to the mesentery of the small intestine that generated a complete obstruction. The bone material was removed and the intestinal flow was reestablished, freeing the obstruction in the small intestine

Perforación colónica por endoprótesis biliar impactada / Colonic perforation due to impacted biliary stent

Introducción. La colocación de endoprótesis biliares es cada día más frecuente por ser actualmente una de las mejores opciones para el tratamiento de patologías de la vía biliar. La migración de las endoprótesis es una de las complicaciones que puede ocurrir en hasta un 10,8 % de los pacientes, pero en muy raras ocasiones llegan a causar una perforación intestinal. Caso clínico. Se trata de una paciente de 61 años, a quien cinco años atrás se le realizó una colangiopancreatografía retrógrada endoscópica por coledocolitiasis. Consultó por presentar dolor abdominal, y al examen físico se encontraron abdomen agudo y plastrón en fosa ilíaca izquierda a la palpación. La tomografía computarizada informó un cuerpo extraño a nivel del colon descendente, con perforación del mismo. Se realizó laparotomía exploratoria y colostomía por perforación del colon sigmoides secundaria a prótesis biliar migrada. Resultados. La paciente evolucionó favorablemente y a los seis meses se realizó el cierre de la colostomía, sin complicaciones. Conclusión. Los pacientes a quienes se les colocan prótesis biliares requieren un seguimiento adecuado para evitar complicaciones que, aunque raras, pueden ocurrir, como la migración intestinal con perforación. El tratamiento de dichas complicaciones se hace por vía endoscópica, laparoscópica o laparotomía en caso de complicación severa.

Introduction. Endoscopic placement of biliary stents is becoming more common every day, as it is currently one of the best options for the treatment of bile duct pathologies. One of the complications that can occur is the migration of the endoprostheses in up to 10.8% of patients, which in very rare cases can cause intestinal perforation. Clinical case. This is a 61-year-old female patient, who underwent endoscopic retrograde cholangiopancreatography five years ago for choledocholithiasis. She consulted due to abdominal pain, with a physical examination that upon palpation documented an acute abdomen and a palpable plastron in the left iliac fossa. The computed tomography revealed a foreign body at the level of the descending colon, with perforation. Exploratory laparotomy and colostomy were performed due to perforation of the sigmoid colon secondary to migrated biliary prosthesis. Results. The patient progressed favorably and six months later the colostomy was closed without complications. Conclusions. Patients who receive biliary stents require adequate follow-up to avoid complications that, although rare, may occur, such as intestinal migration with intestinal perforation. The treatment of these complications can be endoscopic, laparoscopic or laparotomy in case of severe complication.

Ângulo de fase como preditor de massa muscular em pacientes com doença inflamatória intestinal / Phase angle as a predictor of muscle mass in patients with inflammatory bowel disease

ABSTRACT Malnutrition/sarcopenia is frequent in patients with inflammatory bowel diseases (IBD), and results in muscle catabolism, impacting treatment response, postoperative complications, and quality of life. Objective: This study aims to assess whether the phase angle (PhA) is a parameter for predicting reduced muscle mass in patients with IBD. Methods: Adult patients with IBD were included in this cross-sectional study. For the estimation of muscle mass and the calculation of the PhA, we used bioelectrical impedance analysis (BIA). Crohn's disease (CD) and ulcerative colitis (UC) activity scores were defined using the Harvey-Bradshaw index and partial Mayo score, respectively. The area under the ROC curve was calculated to identify the PhA cut-off point for reduced muscle mass. Results: The sample consisted of 145 patients, with 39 (26.9%) with IBD in the active phase. There was a correlation of the PhA with skeletal muscle mass (SMM) (rs 0.35, P<0.001) and with the skeletal muscle mass index (SMI) (rs 0.427, P<0.001), and the associations remained in the most active form (moderate or severe) of IBD. The ROC curve analysis indicated that the cut-offs points of the PhA ≤5.042 for female and PhA ≤6.079 for male can be used to predict muscle mass reduction. Conclusion: The PhA can be considered a predictor of muscle mass reduction in IBD patients, and we can use it for screening and monitoring the evolution of malnutrition.

RESUMO A desnutrição/sarcopenia é frequente em pacientes com doenças inflamatórias intestinais (DII), resultando em catabolismo muscular, com impacto nas respostas aos tratamentos, complicações cirúrgicas e na qualidade de vida. Objetivo: Este estudo tem como objetivo, avaliar se o ângulo de fase (AF) é um parâmetro para a predição de redução de massa muscular em pacientes com DII. Métodos: Pacientes adultos com DII foram incluídos neste estudo transversal. A estimativa da massa muscular e o cálculo do AF foram realizados a partir do exame de bioimpedância elétrica (BIA). As atividades da doença de Crohn e retocolite ulcerativa foram definidas pelo índice Harvey-Bradshaw e escore parcial de Mayo, respectivamente. A área de curva ROC foi calculada para identificar o ponto de corte do AF para a massa muscular reduzida. Resultados: A amostra foi composta por 145 pacientes, sendo 39 (26.9%) com DII em fase ativa. Houve correlação do AF com massa muscular esquelética (MME) (rs 0.35, P<0.001) e com o índice de massa muscular esquelética (IMME) (rs 0.427, P<0.001), mantendo-se as associações na forma mais ativa (moderada ou grave) da DII. A análise da curva ROC indicou que os pontos de corte de AF ≤5.042 para mulheres e ≤6.079 para homens podem ser usados para prever a redução da massa muscular. Conclusão: O AF pode ser considerado um preditor de redução de massa muscular nos pacientes com DII e ser utilizado para triagem e acompanhamento da evolução da desnutrição.

Avaliação da lactoferrina e da calprotectina como marcadores de inflamação intestinal na pancreatite crônica / Evaluating lactoferrin and calprotectin as markers of intestinal inflammation inchronic pancreatitis

ABSTRACT Background: The treatment of chronic pancreatitis does not consistently solve intestinal abnormalities, and despite the implementation of various therapeutic measures, patients often continue to experience persistent diarrhea. Therefore, it is imperative to recognize that diarrhea may stem from factors beyond pancreatic insufficiency, and intestinal inflammation emerges as a potential contributing factor. Objective: The aim of this study was to assess fecal lactoferrin and calprotectin levels as indicators of intestinal inflammation in patients with chronic pancreatitis experiencing persistent diarrhea. Methods: In this study, 23 male patients with chronic pancreatitis primarily attributed to alcohol consumption and presenting with diarrhea (classified as Bristol stool scale type 6 or 7), underwent a comprehensive evaluation of their clinical and nutritional status. Fecal lactoferrin and calprotectin levels were mea­sured utilizing immunoassay techniques. Results: The average age of the participants was 54.8 years, 43.5% had diabetes, and 73.9% were smokers. Despite receiving enzyme replacement therapy and refraining from alcohol for over 4 years, all participants exhibited persistent diarrhea, accompanied by elevated calprotectin and lactoferrin levels indicative of ongoing intestinal inflammation. Conclusion: The findings of this study underscore that intestinal inflammation, as evidenced by elevated fecal biomarkers calprotectin and lactoferrin, may contribute to explaining the persistence of diarrhea in patients with chronic pancreatitis.

RESUMO Contexto: O tratamento da pancreatite crônica não resolve de forma consistente as anomalias intestinais e, apesar da implementação de várias medidas terapêuticas, os pacientes muitas vezes continuam a apresentar diarreia persistente. Portanto, é imperativo reconhecer que a diarreia pode resultar de fatores além da insuficiência pancreática, e a inflamação intestinal surge como um potencial fator contribuinte. Objetivo: O objetivo deste estudo foi avaliar os níveis fecais de lactoferrina e calprotectina como indicadores de inflamação intestinal em pacientes com pancreatite crônica com diarreia persistente. Métodos: Neste estudo, 23 pacientes do sexo masculino com pancreatite crônica atribuída principalmente ao consumo de álcool e apresentando diarreia (classificada na escala de fezes de Bristol tipo 6 ou 7), foram submetidos a uma avaliação abrangente de seu estado clínico e nutricional. Os níveis fecais de lactoferrina e calprotectina foram medidos utilizando técnicas de imunoensaio. Resultados: A idade média dos participantes foi de 54,8 anos, 43,5% tinham diabetes e 73,9% eram fumantes. Apesar de receber terapia de reposição enzimática e abster-se de álcool por mais de 4 anos, todos os participantes apresentaram diarreia persistente, acompanhada por níveis elevados de calprotectina e lactoferrina, indicativos de inflamação intestinal contínua. Conclusão: Os achados deste estudo ressaltam que a inflamação intestinal, evidenciada pelos biomarcadores fecais elevados calprotectina e lactoferrina, pode contribuir para explicar a persistência da diarreia em pacientes com pancreatite crônica.

Uma pesquisa de manejo médico e neuropsiquiátrico em uma coorte brasileira de pacientes com doença inflamatória intestinal (DII) / A medical and neuropsychiatric management survey in a brazilian cohort of patients with inflammatory bowel disease (ibd)

ABSTRACT Inflammatory bowel disease (IBD) can be accompanied by several neurological disorders. Since 2004, we started a Brazilian cohort to assess neuropsychiatric complications in IBD patients. Changes in therapeutic strategy and differences in the prevalence and relevance of neuropsychiatric disorders have been reported in the literature. We conducted a short patient-reported survey about the medical management of IBD (with a special focus on neuropsychiatric management) and its complications. During the enrollment period (9/1/2021 to 8/31/2022), 279 patients with IBD answered the survey (128 patients with ulcerative colitis and 151 with Crohn's disease). This is the first medical management survey aimed to verify the level of perception of IBD patients about their neuropsychiatric conditions. We found a high prevalence of neurologic (59%), psychiatric (32%), and neuropsychiatric co-morbidities (69%). There is a marked discrepancy between the findings of neurological disorders reported in our studies over the first 10 years of the cohort in comparison with the current perception/knowledge among the patients registered in the present management survey. Patients tend to have a better understanding of central rather than peripheral nerve conditions.

RESUMO A doença inflamatória intestinal (DII) pode ser acompanhada por vários distúrbios neurológicos. Desde 2004, iniciamos uma coorte brasileira para avaliar complicações neuropsiquiátricas em pacientes com DII. Mudanças na estratégia terapêutica e diferenças na prevalência e relevância dos transtornos neuropsiquiátricos têm sido relatadas na literatura. Realizamos uma breve pesquisa relatada pelos pacientes sobre o manejo médico da DII (com foco especial no manejo neuropsiquiátrico) e suas complicações. Durante o período de 01/09/2021 a 31/08/2022, 279 pacientes com DII responderam à pesquisa (128 pacientes com retocolite ulcerativa e 151 com doença de Crohn). Esta é a primeira pesquisa de gestão médica que visa verificar o nível de percepção dos pacientes com DII acerca de suas condições neuropsiquiátricas. Encontramos uma alta prevalência de comorbidades neurológicas (59%), psiquiátricas (32%) e neuropsiquiátricas (69%). Há uma discrepância marcante entre os achados de distúrbios neurológicos relatados em nossos estudos durante os primeiros 10 anos da coorte em comparação com a percepção/conhecimento atual entre os pacientes da presente pesquisa de manejo. Os pacientes tendem a ter uma melhor compreensão das condições que afetam o sistema nervoso central do que as que afetam o sistema nervoso periférico.

Taxas de hospitalização, uso de biológicos e cirurgias em doenças inflamatórias intestinais: uma análise comparativa entre os sistemas público e privado de saúde em centro de referência da América Latina / Hospitalization, use of biologics and surgery rates in inflammatory bowel diseases: a single-centre comparative analysis between public and private healthcare systems in a tertiary unit from latin america

ABSTRACT Background: Inflammatory bowel diseases (IBD) have rising incidence and prevalence rates globally. In IBD, there are scarce stu­dies comparing differences between patients according to socioeconomic status. Our aim was to comparatively evaluate hospitalizations, use of biologics and rates of surgery in patients with IBD between public and private healthcare systems. Methods: Single-center retrospective cohort study in patients with IBD from a tertiary referral unit from Latin America, between 2015 and 2021. CD and UC patients were classified into two subgroups: public and private systems. Demographic characteristics, hospitalizations, need for surgery and biologics were compared. Results: A total of 500 patients were included, 322 with CD and 178 with UC. CD-related hospitalizations were frequently observed in both healthcare systems (76.28% in private and 67.46% in public). More than half of the patients had been submitted to one or more CD-related abdominal surgery, with no significant difference between the subgroups. Although there was no difference in the rates of use of biological therapy in CD subgroups, infliximab was more used in the public setting (57.69% vs 43.97%). There was no difference in UC-related hospitalizations between the subgroups (public 30.69% and private 37.66%) as well as the rates of colectomy (public: 16.83%, private: 19.48%). Biologics were prescribed almost twice as often in private as compared to public (45.45 vs 22.77%). Conclusion: There were no differences in the rates of hospitalization and abdominal surgery between the systems. In patients with UC, there was greater use of biological therapy in the private healthcare setting.

RESUMO Contexto: As doenças inflamatórias intestinais (DII) têm taxas crescentes de incidência e prevalência em todo o mundo. Na DII, são escassos os estudos comparando as diferenças entre os pacientes de acordo com o nível socioeconômico. Objetivo: Nosso objetivo foi avaliar comparativamente as hospitalizações, o uso de biológicos e as taxas de cirurgia em pacientes com DII entre os sistemas público e privado de saúde. Métodos: Estudo de coorte retrospectivo unicêntrico em pacientes com DII de uma unidade terciária de referência da América Latina, entre 2015 e 2021. Os pacientes com DC (doença de Crohn) e retocolite ulcerativa foram classificados em dois subgrupos: sistema público e privado. Características demográficas, hospitalizações, necessidade de cirurgia e biológicos foram comparadas. Resultados: Foram inclusos 500 pacientes, sendo 322 com DC e 178 com retocolite ulcerativa. Internações por DC foram frequentes em ambos os sistemas de saúde (76,28% na rede privada e 67,46% na rede pública). Mais da metade dos pacientes havia sido submetida a uma ou mais cirurgias abdominais relacionadas à DC, sem diferença significativa entre os subgrupos. Embora não tenha havido diferença nas taxas de uso de terapia biológica nos subgrupos de DC, o infliximabe foi mais utilizado no ambiente público (57,69% vs 43,97%). Não houve diferença nas internações relacionadas a retocolite ulcerativa entre os subgrupos (público 30,69% e privado 37,66%) e nas taxas de colectomia (público: 16,83%, privado: 19,48%). Os biológicos foram prescritos quase duas vezes mais no privado do que no público (45,45 vs 22,77%). Conclusão: Não houve diferença nas taxas de internação hospitalar e de cirurgia abdominal entre os sistemas. Nos pacientes com retocolite ulcerativa, houve maior utilização da terapia biológica no setor privado de saúde.

First known case of human bertiellosis in a child in Paraná, Brazil / Primeiro caso conhecido de bertielose humana em uma criança no Paraná, Brasil

ABSTRACT Objective: To describe the first known case of human Bertiellosis in Paraná (Brazil). Case description: A 6-year-old male residing in the Brazilian state of Paraná was suffering from intermittent nonspecific abdominal pain and abdominal distension, associated with expulsion of live tapeworms in his feces for 7 months. He had a history of interaction with monkeys on an island. His first feces analysis was inconclusive, with an initial hypothesis of an atypical Taenia. However, after additional research, the parasitologist identified pregnant proglottids of Bertiella sp. The patient was initially treated with an unknown dosage of albendazole and nitazoxanide, as it was believed he had been infected with Taenia sp. Since the symptoms persisted, praziquantel 10 mg/kg was prescribed without further proglottids elimination. Comments: Human Bertiellosis is a rare zoonosis, with less than one hundred cases reported. However, it is a cause of chronic abdominal pain and should be kept as a differential diagnosis, especially in cases reporting recurrent tapeworm expulsion in feces and refractory treatment with albendazole.

RESUMO Objetivo: Descrever o primeiro caso conhecido de bertielose humana no Paraná, Brasil. Descrição do caso: Criança de seis anos do sexo masculino, residente no Paraná, Brasil, apresentava dor abdominal inespecífica intermitente e distensão abdominal, associadas à expulsão de helmintos vivos em suas fezes havia sete meses. Tinha um histórico de interação com macacos em uma ilha. Sua primeira análise de fezes foi inconclusiva, com hipótese inicial de uma Taenia atípica. No entanto, após pesquisas adicionais, o parasitologista identificou proglótides gravídicas de Bertiella sp. O paciente foi inicialmente tratado com uma dosagem desconhecida de albendazol e nitazoxanida, pois se acreditava que havia sido infectado por Taenia sp. Diante da persistência dos sintomas, foi prescrito praziquantel 10 mg/kg, sem mais eliminação de proglótides. Comentários: A bertielose humana é uma zoonose rara, com menos de cem casos relatados. No entanto, é uma causa de dor abdominal crônica e deve ser mantida como diagnóstico diferencial, principalmente nos casos que relatam expulsão recorrente de helmintos nas fezes e que são refratários ao tratamento com albendazol.

Dual x-ray absorptiometry monitoring in pediatric short bowel syndrome: an integrative review / Monitorização por absortometria com duplo raio X na síndrome do intestino curto pediátrica: uma revisão integrativa

ABSTRACT Objective: To analyze the bone health of pediatric patients with short bowel syndrome intestinal failure (SBS-IF). Data source: An integrative literature review was performed using the data published in the MEDLINE-PubMed and Scientific Electronic Library Online (SciELO) databases between January 2010 and April 2021, and through a manual search of the reference lists of relevant studies. Studies were included if they assessed bone mineral density by the Dual X-Ray Absorptiometry (DXA) technique, incorporated pediatric patients (up to 20 years of age) with SBS under parenteral nutrition (PN) and were written in English. Eleven primary sources met the inclusion criteria for this study. Data synthesis: Pediatric patients with SBS-IF under long-term parenteral nutrition experienced frequent changes in bone metabolism, leading to osteoporotic fractures and growth failure. These patients have deficiencies in multiple nutrients, such as calcium, magnesium, phosphorus, and vitamin D. Consequently, there are variations in the secretion and regulation of the parathyroid hormone. In addition, the pharmacotechnical limitations related to calcium and phosphorus in the PN solution, use of glucocorticoids, and difficulty performing physical activity are risk factors for the development of metabolic bone disease in pediatric patients with SBS-IF. Conclusions: Low bone mineral density was associated with a high risk of developing osteoporosis, fractures, and growth deficiency in pediatric patients with SBS-IF on PN therapy in the long term.

Objetivo: Analisar a saúde óssea de pacientes pediátricos com síndrome do intestino curto — falência intestinal (SIC-FI). Fontes de dados: Revisão integrativa da literatura usando os dados publicados nas bases de dados Medical Literature Analysis and Retrieval System Online/ United States National Library of Medicine (MEDLINE/PubMed) e Scientific Electronic Library Online (SciELO) entre janeiro de 2010 e abril de 2021 e por meio de busca manual nas listas de referências de estudos relevantes. Foram incluídos estudos em inglês que avaliaram a densidade mineral óssea pela técnica de absorciometria de raio X duplo (DXA), incluíram pacientes pediátricos (até 20 anos de idade) com SIC sob terpia nutricional parenteral. Onze fontes primárias preencheram os critérios de inclusão para este estudo. Síntese dos dados: A pesquisa revelou que pacientes pediátricos com SIC-FI sob nutrição parenteral (NP) de longo prazo tiveram alterações frequentes no metabolismo ósseo, levando a fraturas osteoporóticas e falha de crescimento. Esses pacientes apresentam deficiências de múltiplos nutrientes, como cálcio, magnésio, fósforo e vitamina D. Consequentemente, houve variações na secreção e regulação do hormônio da paratireoide. Além disso, as limitações farmacotécnicas relacionadas ao cálcio e fósforo na solução de NP, o uso de glicocorticoides e dificuldade para realizar atividade física são fatores de risco para o desenvolvimento de doença óssea metabólica em pacientes pediátricos com SIC-FI. Conclusões: A baixa densidade mineral óssea foi associada a um alto risco de desenvolver osteoporose, fraturas e deficiência de crescimento em pacientes pediátricos com SIC-FI sob terapia nutricional parenteral em longo prazo.

Isquemia mesentérica aguda: un desafío de la medicina. Reporte de un caso

La isquemia intestinal aguda es una emergencia vascular provocada por fenómenos oclusivos y no oclusivos de la circulación mesentérica arterial y venosa, de difícil diagnóstico y pronóstico ominoso. Su incidencia va en aumento paulatino con el decurso de los años, asociada fundamentalmente al envejecimiento de la población. La tasa de mortalidad es elevada a pesar de los avances en el campo de la imagenología. Suele diagnosticarse de forma tardía, cuando está establecido el daño isquémico intestinal de carácter irreversible. El elemento imprescindible e indispensable lo constituye el tiempo que trascurre hasta la cirugía, por lo que su diagnóstico sigue siendo un reto clínico. El tratamiento exige medidas médicas intensivas, al igual que cirugía de revascularización y resección del intestino necrosado. Por desdicha, el examen físico y los hallazgos de laboratorio no son sensibles ni específicos para su diagnóstico. Teniendo en cuenta estos elementos, se presenta el caso de una paciente de 38 años con clínica difusa de vómitos, diarrea y dolor abdominal progresivo, que requirió intervención quirúrgica de urgencia con diagnóstico transoperatorio de isquemia mesentérica aguda. Durante su estancia hospitalaria se relaparotomizó en dos ocasiones, mantuvo soporte ventilatorio e inotrópico por fallo multiorgánico en la Unidad de Cuidados Intensivos, mostrando una adecuada evolución posquirúrgica. El objetivo de esta presentación es enfatizar en la clínica como elemento fundamental para abordar de forma correcta esta entidad en un medio hospitalario de limitados recursos diagnósticos imagenológicos, al abordar conceptos teóricos recientes y facilitar una adecuada actuación en la toma de decisiones.

Acute intestinal ischemia is a vascular emergency caused by occlusive and non-occlusive phenomena of the mesenteric arterial and venous circulation of difficult diagnosis and ominous prognosis. Its incidence is gradually increasing over the years, mainly associated with the ageing of the population. The mortality rate is high despite advances in the field of imaging. It is usually diagnosed late, when irreversible ischemic intestinal damage is established. The essential and indispensable element is the time that elapses until surgery, so its diagnosis continues to be a clinical challenge. Treatment requires intensive medical measures, as well as revascularization surgery and resection of the necrotic intestine. Unfortunately, physical examination and laboratory findings are neither sensitive nor specific for its diagnosis. Taking these elements into account, the authors present the case of a 38-year-old female patient with diffuse symptoms of vomiting, diarrhea and progressive abdominal pain that required emergency surgery with intraoperative diagnosis of acute mesenteric ischemia. During her hospital stay, she underwent re-laparotomy twice, maintained ventilatory and inotropic support due to multi-organ failure in the Intensive Care Unit, showing an adequate post-surgical evolution. The objective of this presentation is to emphasize in the clinic as a fundamental element to correctly address this entity in a hospital environment with limited imaging diagnostic resources by addressing recent theoretical concepts and facilitating adequate action in decision-making.

Mechanism of Bushen Yijing Method in Treatment of Oligoasthenozoospermia Based on Intestinal Microbiota / 中国实验方剂学杂志

Oligoasthenozoospermia is the main cause of male infertility， with complex and diverse causes. Currently， there are still some unclear causes of oligoasthenozoospermia in clinical practice， known as idiopathic oligoasthenozoospermia. With the development of high-throughput sequencing technology， it has been found that intestinal microbiota disorder may be an important promoting factor for the onset of oligoasthenozoospermia. Traditional Chinese medicine believes that "deficiency of kidney essence" is the core pathogenesis of oligoasthenozoospermia. In clinical practice， the method of tonifying the kidney and strengthening the essence has a significant therapeutic effect on oligoasthenozoospermia， but its mechanism of action has not been fully elucidated. Based on the basic theories of traditional Chinese medicine and molecular biology research， it has been found that there is a similarity between "kidney essence" and intestinal microbiota. During the onset of oligoasthenozoospermia， the disorder of intestinal microbiota has similarities with the pathogenesis of "deficiency of kidney essence" in traditional Chinese medicine. Moreover， traditional Chinese medicine for tonifying the kidney and strengthening the essence can regulate the disorder of intestinal microbiota， which may be one of the effective mechanisms for the treatment of oligoasthenozoospermia with the Bushen Yijing method. Based on this， this article explored the mechanism of Bushen Yijing method of traditional Chinese medicine in treating oligoasthenozoospermia from the perspective of intestinal microbiota， so as to provide new ideas for the treatment of oligoasthenozoospermia with traditional Chinese medicine.

Pathogenesis of Diabetes from Theory of Spleen Deficiency Causing Diabetes Based on Intestinal Innate Immunity / 中国实验方剂学杂志

In western medicine， the small intestine anatomically belongs to the digestive system and is also an important immune organ of the body. The innate immune system of the small intestine consists of a tissue barrier， innate immune cells， and innate immune molecules. The dysfunction of any part can cause metabolic disorders and eventually lead to diabetes. In the pathogenesis of diabetes， traditional Chinese medicine （TCM） has the theory of ''spleen deficiency causing diabetes''， which points out that the impaired spleen function results in inadequate transformation， impaired essence spread， and turbidity by essence accumulation， which is the core pathological link of blood glucose metabolism disorder in diabetes. In terms of the relationship between the small intestine and the spleen， the theory of TCM holds that the small intestine is located in the abdomen and the abdomen is dominated by the spleen. The digestion， absorption， and endocrine functions of the small intestine are also similar to the functions of spleen in governing movement and transformation and spreading essence by virtue of spleen Qi. Therefore， the anatomical and physiological functions of the small intestine in western medicine are closely related to the spleen in TCM. At the same time， the spleen is closely related to the innate immune function of the small intestine in TCM. The spleen participates in the generation and distribution of defense Qi， and the process of defense Qi playing the external function is similar to the process of the activation of the innate immune response. The spleen is also an important organ involved in fluid metabolism， which can cooperate with the lung and kidney to timely remove turbid fluid from the body. It can also work with the stomach as the hub of Qi ascending and descending and regulate the physiological activities of "clear Yang" and "turbid Yin"， so as to ensure the homeostasis of the internal environment of the body， which is the basis for maintaining the normal function of the innate immunity of the small intestine. Therefore， taking "spleen deficiency causing diabetes" as a bridge， the theory of TCM and western medicine were combined to explain the relationship between small intestinal innate immunity imbalance and the pathogenesis of diabetes from the perspective of TCM， which is helpful to understand the pathogenesis of diabetes in a deeper level and also provide a new perspective and new way for the prevention and treatment of this disease with TCM.

Mechanism of Qingfei Huatan Zhuyu Decoction in Treatment of COPD Based on "Lung and Intestinal Co-treatment" / 中国实验方剂学杂志

ObjectiveTo observe the effect of Qingfei Huatan Zhuyu decoction on the lung and intestinal function of rats with chronic obstructive pulmonary diseases （COPD） and explore the deep-seated mechanism of its embodiment of lung and intestinal co-treatment. MethodA total of 60 Wistar rats were randomly divided into six groups， with 10 rats in each group， and the groups were control group， model group， acute syrup group （10 g·kg-1·d-1）， and low， medium， and high-dose groups （10， 15， 20 g·kg-1·d-1） of Qingfei Huatan Zhuyu decoction. The COPD rat model was established by lipopolysaccharide tracheal drip combined with the smoke inhalation method， and the acute syrup group and the Qingfei Huatan Zhuyu decoction group were administered by gavage with corresponding dose concentrations respectively， while the rest groups were controlled by saline gavage， and the lung function and blood gas indexes of rats were monitored after the last administration. The histopathological changes in the lung and intestine were observed microscopically. The expression of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （IgA） in colon tissue were measured by enzyme-linked immunosorbent assay （ELISA）. The biochemical indexes such as serum diamine oxidase （DAO）， D-lactic acid， and malondialdehyde （MDA） were measured. Immunohistochemistry was used to detect the expression of tight junction protein （Occludin） in rat colon tissue. The expression of F4/80 positive alveolar macrophages in rat lung tissue， and the expression of α-actin （α-SMA） and colonic atresia small band protein-1 （ZO-1） were determined by immunofluorescence. The protein expression of p-NF-κB p65， NF-κB p65， p-p38 MAPK， and p-p38 MAPK and the expression of Occludin and ZO-1 in colon tissue were detected in rat lung tissue by Western blot. ResultCompared with the normal group， the model group had pulmonary dysfunction， reduced forced vital capacity （FVC）， arterial partial oxygen pressure （PaO2）， arterial oxygen saturation （SaO2）， and dynamic lung compliance （Cdyn） （P<0.01）， and the pathological changes in the lung and intestine were obvious. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were increased （P<0.05，P<0.01）， and the protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue was increased. The expression of F4/80 positive macrophages in lung tissue was enhanced. The expression of IgA， Occludin， and ZO-1 in colon tissue decreased （P<0.05，P<0.01）. Compared with the model group， the pulmonary function of the rats in the acute syrup group and groups of Qingfei Huatan Zhuyu decoction was significantly improved， and the FVC， PaO2， SaO2， and Cdyn were increased （P<0.05， P<0.01）. The pathological changes in the lung and intestine were significant. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were decreased （P<0.05，P<0.01）， and the expressions of F4/80 positive macrophages in lung tissue were decreased （P<0.01）. The protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue decreased （P<0.01）， and the expression of IgA， Occludin， and ZO-1 in colon tissue increased （P<0.01）. ConclusionQingfei Huatan Zhuyu decoction can effectively reduce the symptoms of COPD rats， and its mechanism of action is related to inhibiting the inflammatory response of lung tissue and improving the barrier function of the intestinal mucosa.

Improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis and its mechanism / 中国药房

OBJECTIVE To investigate the improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis （UC） and its mechanism. METHODS UC rat models were established， and 70 rats with successful modeling were randomly divided into model group， limonin low-， medium-， and high-dose groups （12.5， 25， 50 mg/kg）， and sulfasalazine group （positive control group，500 mg/kg）， with 14 rats in each group. Another 14 rats were selected as the control group. After modeling， each group was given the corresponding drug or equal amount of normal saline， once a day， for 2 weeks. Twenty-four hours after the last administration， the general condition of rats was observed and the body weight was measured， and colon tissue was collected for colonic mucosal damage index （CMDI） scoring； the levels of interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） in colon tissue were detected； the pathological changes of colon tissue were observed； the protein expressions of Claudin-1， Occludin， ZO-1， high mobility group protein B1 （HMGB1） and receptor for advanced glycation end products （RAGE） in colon tissue were detected； fecal 16S rRNA sequencing was used to detect the relative abundance of zhangxiaxia5287@163.com intestinal microbiota in rats. RESULTS Compared with the control group， the rats in the model group were in poor mental state， with darker fur， irritable mood， disordered arrangement of colon glands， inflammatory cell infiltration， cell necrosis and edema； CMDI score， the levels of IL-1β， IL-6 and TNF-α， protein expressions of HMGB1 and RAGE in colon tissue， the relative abundance of Proteobacteria and Bacteroidetes were significantly increased （P＜0.05）； body weight， the protein expressions of Claudin-1， Occludin and ZO-1 in colon tissue， the relative abundance of Firmicutes in the intestine were significantly decreased （P＜0.05）. Compared with the model group， general situation and pathological damage of colonic tissue in limonin groups were improved， the levels of the above indicators were significantly reversed （P＜0.05）， and in a dose-dependent manner （P＜0.05）； there was no significant difference in various indexes between sulfasalazine group and limonin high-dose group （P＞0.05）. CONCLUSIONS Limonin can improve intestinal injury and intestinal flora disturbance in UC model rats， the mechanism of which may be associated with the down-regulation of HMGB1/RAGE signaling pathway.

Effect of Intestinal Microecology on Diabetic Kidney Disease Based on Yin-Yang Theory / 中国实验方剂学杂志

Diabetic kidney disease （DKD） is the main cause of end-stage renal disease. Its high prevalence， mortality rate， and medical cost bring a heavy economic burden to society and families， and DKD has become one of the most important public health problems. Intestinal microecology is the most important and complex micro-ecosystem in the human body， which is involved in important life activities such as material and energy metabolism， immune system regulation， and signal transduction， thereby maintaining the dynamic balance of the human internal environment. The dynamic balance between the intestinal microecology and the body is essentially a Yin-Yang balance. Once this balance is broken， intestinal microbiota imbalance， intestinal mucosal barrier damage， immune dysfunction， and reduction of metabolite short-chain fatty acids （SCFAs） will occur， which play an important role in the progression of DKD. From the perspective of the Yin-Yang theory of traditional Chinese medicine （TCM）， the imbalance of intestinal microecology in DKD is equivalent to the excessive or insufficient constraint of Yin and Yang， or Yin deficiency affecting Yang， or Yang deficiency affecting Yin， or waning and waxing of Yin and Yang. For different pathogenesis changes， "Yin disease treated through Yang"， "treating Yin for Yang"， or "treating Yang for Yin" methods are adopted to regulate intestinal microbiota， inhibit immune inflammation， protect intestinal mucosal barrier， and increase SCFAs through TCM， thereby reconciling Yin and Yang to achieve the condition where "Yin is at peace and Yang is compact". Based on the Yin-Yang theory， this paper intended to interpret the scientific connotation of TCM in the treatment of DKD with intestinal microecology as the target and TCM in the treatment of DKD by regulating intestinal microecology as the breakthrough point to provide a novel insight for the occurrence and development of DKD and the mechanism of TCM.

Chinese Medicine in Treatment of Ulcerative Colitis by Regulating Intestinal Flora： A Review / 中国实验方剂学杂志

Ulcerative colitis （UC） is a chronic， non-specific inflammatory bowel disease. The pathogenesis of this disease is complex and is attributed to multiple factors. Intestinal mucosal barrier damage is the basic pathological change of UC， and intestinal flora disorder is one of the important characteristics of UC. Intestinal flora plays a key role in the pathological process of UC by regulating intestinal mucosal immunity and inflammatory response to repair the damaged intestinal mucosal barrier. At present， western medicine has the advantages of rapid action onset and significant short-term efficacy， but the curative effect of long-term use is not good， accompanied by many adverse reactions， causing great physical and mental pain to patients. Therefore， it is urgent to explore new treatment methods with definite long-term efficacy and mild adverse reactions. A large number of studies have shown that Chinese medicine can regulate intestinal flora through multiple targets in an all-around way， restore the homeostasis of the flora， and repair the damaged intestinal mucosal barrier， thereby inhibiting the progression of UC. Numerous studies have shown that the active components， monomers， and compounds of Chinese medicine can effectively antagonize UC by regulating the intestinal flora to improve the intestinal mucosal immunity， reduce the inflammatory response of the intestinal mucosa， and restore the normal physiological function of the intestinal mucosal barrier， providing a new strategy for UC prevention and treatment. Although there are some studies of the regulation of intestinal flora by Chinese medicine to prevent and treat UC， those studies have the shortcomings of systematic and comprehensive inadequacy. Therefore， based on the research status of UC， intestinal flora， and Chinese medicine treatment， this study reviewed the relationship between intestinal flora and UC and clarified the key role of intestinal flora in the occurrence and development of UC. At the same time， this paper comprehensively summarized the Chinese medicine that targeted the regulation of intestinal flora for the treatment of UC in the past five years to provide new strategies and ideas for UC treatment.

Transporter-mediated Nano-delivery System in Promoting Oral Absorption of Drugs：A Review / 中国实验方剂学杂志

Oral administration is the most convenient way of drug delivery， but due to the existence of intestinal barrier， the oral bioavailability of drugs is generally low， especially for drugs with low water solubility， poor permeability and macromolecules. For decades， researchers have demonstrated that nano-delivery system is one of the most effective strategies to solve this problem， but nano-delivery systems have shown limited improvement in the oral bioavailability of drugs. Therefore， researchers have proposed to use transporter-mediated nano-delivery systems to promote the oral absorption of drugs. The intestinal tract were highly expressed as a transporter for ingesting various nutrients（such as glucose， oligopeptides and bile acids）， which was an excellent target of oral drug delivery system. Its substrate were modified on the nano-delivery system， and the loaded drugs could cross the intestinal barrier and enter the systemic circulation more efficiently through the targeting effect of transporters. At present， more and more evidences supported the potential of transporters in the field of oral drug delivery system. Therefore， this paper reviewed the research on intestinal transporters-mediated nano-delivery system to promote oral absorption of drugs， including the distribution of intestinal transporters， three strategies of transporter substrate modification， the transport properties of different types of transporters and their effects of mediating the nano-delivery system for promoting the oral absorption of drugs or treating diseases， with the aim of providing an important theoretical reference for the development of intestinal targeted nano-delivery systems.