Urinary excretion of gluten immunoreactive peptides as an indicator of gastrointestinal function after fasting and dietary provocation in healthy volunteers.

Introduction: Understanding intestinal permeability is paramount for elucidating gastrointestinal health and pathology. The size and nature of the molecule traversing the intestinal barrier offer crucial insights into various acute and chronic diseases, as well as the evolution of some conditions. This study aims to assess the urinary excretion kinetics of gluten immunogenic peptides (u-GIP), a unique class of dietary peptides detectable in urine, in volunteers under controlled dietary conditions. This evaluation should be compared to established probes like lactulose, a non-digestible disaccharide indicative of paracellular permeability, and mannitol, reflecting transcellular permeability. Methods: Fifteen participants underwent simultaneous ingestion of standardized doses of gluten (10 g), lactulose (10 g), and mannitol (1 g) under fasting conditions for at least 8 hours pre-ingestion and during 6 hours post-ingestion period. Urine samples were collected over specified time intervals. Excretion patterns were analyzed, and correlations between the lactulose-to-mannitol ratio (LMR) and u-GIP parameters were assessed. Results: The majority of u-GIP were detected within the first 12 hours post-ingestion. Analysis of the variability in cumulative excretion across two sample collection ranges demonstrated that lactulose and u-GIP exhibited similar onset and excretion dynamics, although GIP reached its maximum peak earlier than either lactulose or mannitol. Additionally, a moderate correlation was observed between the LMR and u-GIP parameters within the longest urine collection interval, indicating potential shared characteristics among permeability pathways. These findings suggest that extending urine collection beyond 6 hours may enhance data reliability. Discussion: This study sheds light on the temporal dynamics of u-GIP in comparison to lactulose and mannitol, established probes for assessing intestinal permeability. The resemblance between u-GIP and lactulose excretion patterns aligns with the anticipated paracellular permeability pathway. The capacity to detect antigenic food protein fragments in urine opens novel avenues for studying protein metabolism and monitoring pathologies related to the digestive and intestinal systems.

The effect of rifaximin and lactulose treatments to chronic hepatic encephalopathy rats: An [18F]PBR146 in-vivo neuroinflammation imaging study.

INTRODUCTION: Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of liver diseases characterized by neuroinflammation. The efficacies of nonabsorbable rifaximin (RIF) and lactulose (LAC) have been well documented in the treatment of HE. [18F]PBR146 is a translocator protein (TSPO) radiotracer used for in vivo neuroinflammation imaging. This study investigated anti-neuroinflammation effect of RIF or/and LAC in chronic HE rats by [18F]PBR146 micro-PET/CT. METHODS: Bile duct ligation (BDL) operation induced chronic HE models, and this study included Sham+normal saline (NS), BDL+NS, BDL+RIF, BDL+LAC, and BDL+RIF+LAC groups. Behavioral assessment was performed to analyze the motor function, and fecal samples were collected after successfully established the chronic HE model (more than 28 days post-surgery). In addition, fecal samples collection and micro-PET/CT scans were performed sequentially. And we also collected the blood plasma, liver, intestinal, and brain samples after sacrificing the rats for further biochemical and pathological analyses. RESULTS: The RIF- and/or LAC-treated BDL rats showed similar behavioral results with Sham+NS group, while the treatment could not reverse the biliary obstruction resulting in sustained liver injury. The RIF or/and LAC treatments can inhibit IFN-γ and IL-10 productions. The global brain uptake values of [18F]PBR146 in BDL+NS group was significantly higher than other groups (p < .0001). The brain regions analysis showed that the basal ganglia, hippocampus, and cingulate cortex had radiotracer uptake differences among groups (all p < .05), which were consistent with the brain immunohistochemistry results. Sham+NS group was mainly enriched in Christensenella, Coprobacillus, and Pseudoflavonifractor. BDL+NS group was mainly enriched in Barnesiella, Alloprevotella, Enterococcus, and Enterorhabdus. BDL+RIF+LAC group was enriched in Parabacteroides, Bacteroides, Allobaculum, Bifidobacterium, and Parasutterella. CONCLUSIONS: RIF or/and LAC had anti-neuroinflammation in BDL-induced chronic HE rats with gut microbiota alterations. The [18F]PBR146 could be used for monitoring RIF or/and LAC treatment efficacy of chronic HE rats.

Hepatic veno-occlusive disease complicated with extreme hyperammonaemia (920 µmol/L) treated with defibrotide, lactulose, rifampin and haemodialysis.

Hepatic veno-occlusive disease (VOD)/sinusoidal obstructive syndrome (SOS) is a severe complication that can occur following haematopoietic stem cell transplant (HSCT) with high-intensity conditioning chemotherapy regimens. Severe VOD/SOS, often characterised by multiorgan failure, is associated with a high mortality rate. This case report details the complex clinical course of a male patient in his mid-20s, recently diagnosed with B cell acute lymphoblastic leukaemia, who underwent allogeneic HSCT. Based on the 2023 European Society for Blood and Marrow Transplantation (EBMT) criteria, the patient developed very severe VOD/SOS, prompting immediate treatment with defibrotide. Unexpectedly, he developed profound hyperammonaemia exceeding 900 µmol/L, leading to encephalopathy and cerebral oedema. Despite aggressive interventions including defibrotide, lactulose, rifampin and haemodialysis, the patient passed away due to cerebral oedema and pulseless electrical activity arrest. We theorise the hyperammonaemia is disproportionate to his hepatic dysfunction and is possibly secondary to an acquired defect of the urea synthesis consistent with idiopathic hyperammonaemia, a rare complication in patients receiving intense conditioning chemotherapy.

NFSI mediated C3-ether oxidation of glycals for the synthesis of hex-3-enuloses.

Hex-3-enuloses constitute a vital carbohydrate synthetic intermediate that provide access to wide range of chiral molecules through diverse derivatizations. Herein we report synthesis of these fascinating scaffolds by oxidation of C3-ether protections on glycals in presence of N-fluorobenzenesulfonimide (NFSI) under Cu(I) catalysed conditions. Benzyl, methyl and silyl ethers have been efficiently oxidized to the carbonyl group. The oxidation has been found to be highly regioselective where an array of protecting groups were tolerant to the reaction conditions. Pyranosyl glycals from various commercially available sugars have been studied in this work to evaluate the broad substrate scope.

Colonoscopic laxative instillation for the fecal-loaded colon: a case series

Context: Postoperative, critically ill, and elderly patients often have fecal loading or impaction. In a few such patients, disimpaction of fecalomas and colon cleansing are difficult. Bowel obstruction, megacolon, lower gastrointestinal bleeding, and gut perforation are complications that may ensue. Oral laxatives or enemas may only be partially effective. Surgical intervention may be needed for salvage or to treat complications. Series and Design: Fourteen hospitalized cases with defecation disorder due to fecal loading of the colon were enrolled for retrospective analysis. Colonoscopic instillation of mannitol and/or lactulose was undertaken as an intervention when the use of oral laxatives was either ineffective or unfeasible, and enema had yielded poor results. Results: Ten patients had satisfactory outcomes for fecal clearance, whereas four patients with poor or incomplete responses underwent repeat interventions or surgery. No significant complications were encountered due to this therapy. Conclusion: Colonoscopic instillation of mannitol or lactulose in fecal-loaded critically ill patients results in a safe and satisfactory fecal clearance. (AU)

The impact of small intestinal bacterial overgrowth on the growth of children and adolescents / Impacto do sobrecrescimento bacteriano no intestino delgado sobre o peso e a estatura de crianças e adolescentes

ABSTRACT Objective: To evaluate the association between small intestinal bacterial overgrowth (SIBO) and weight and height impairment in children and adolescents with gastroenterology diseases. Methods: Observational and retrospective study. All 162 patients aged less than 19 years old who underwent breath test in search of SIBO between 2011 and 2016 were studied. Breath test was collected after the intake of 10 grams of lactulose. The concentration of hydrogen and methane was measured for 180 minutes after the beginning of the test by 12i QuinTronMicroLyzer device. Results: SIBO was identified in 51 (31.5%) patients. There was no difference between the age of those with (mean=8.7y.o; 25th and 75th percentile: 4.6 and 11.3) and without (mean=7.9y.o 25th and 75th percentile: 4.8 and 12.2) SIBO (p=0.910). There was no association between gender and SIBO (male 26.3% vs. female 36.3%, p=1.00). A lower median of height-for-age Z score (mean=-1.32; 25th and 75th percentile: -2.12 and -0.08 vs. mean=-0.59; 25th and 75th percentile: -1.57 and 0.22; p=0.04) was demonstrated in children with SIBO when compared with children without it. There was no difference between the BMI-for-age Z score of patients with (mean=-0.48) and without SIBO (mean=-0.06) (p=0.106). The BMI of patients with SIBO (median=15.39) was lower than of those without it (median=16.06); however, the statistical analysis was not significant (p=0.052). The weight-for-age Z score was lower in patients with SIBO (mean=-0.96) than in those without SIBO (mean=-0.22) (p=0.02) Conclusions: Children and adolescents with SBIO associated with diseases of the gastrointestinal tract have lower weight and height values.

RESUMO Objetivo: Avaliar a existência de associação entre sobrecrescimento bacteriano no intestino delgado (SBID) e comprometimento de peso e estatura em crianças e adolescentes com doenças do aparelho digestivo. Métodos: Estudo observacional e retrospectivo em ambulatório de gastroenterologia pediátrica. Foram incluídos todos os 162 pacientes com idade inferior a 19 anos que realizaram teste respiratório para pesquisa de SBID entre 2011 e 2016. O teste respiratório foi realizado após ingestão de dez gramas de lactulose. Foram determinadas as concentrações de hidrogênio e metano em aparelho 12i QuinTron MicroLyzer até 180 minutos após o início do teste respiratório. Resultados: SBID foi caracterizado em 51 (31,5%) dos 162 pacientes. Não houve diferença na idade das crianças com (mediana=8,7 anos; percentil 25-75: 4,6-11,3) e sem (mediana=7,9 anos; percentil 25-75: 4,8-12,2) SBID (p=0,910). Não se observou associação entre SBID e sexo (masculino 27,4% e feminino 36,6%; p=0,283). O escore Z da estatura-idade nos pacientes com SBID (mediana=-1,32; percentil 25-75: -2,12—0,08) foi menor (p=0,040) do que naqueles sem SBID (mediana=-0,59; percentil 25-75: -1,57-0,22). Na comparação do escore Z de índice de massa corpórea-idade não foi observada diferença entre os grupos com (média=-0,489±1,528) e sem (média=-0,067±1,532) SBID (p=0,106). Nos pacientes com menos de 10 anos de idade, o escore Z de peso-idade foi menor nos pacientes com SBID (média=-0,968±1,359) do que nos sem SBID (média=-0,223±1,584) (p=0,026). Conclusões: Crianças e adolescentes com SBID associado a doenças do trato gastrintestinal apresentam menores valores de peso e estatura.

Effect of polyethylene glycol versus lactulose on abdominal pain in children occult constipation: a randomized controlled study: un estudio controlado aleatorio / Efecto del polietilenglicol versus lactulosa sobre el dolor abdominal en el estreñimiento oculto en niños

Introduction and aim: Functional abdominal pain (FAP) is one of the major gastrointestinal complaints in childhood. Studies have reported occult constipation (OC) as one of the leading causes of abdominal pain. Recent researches have proposed laxatives as potent therapeutic targets for abdominal pain in patients with OC. However, no study has compared effect of poly ethylene glycol (PEG) and lactulose on occult constipation. Materials and methods: 51 patients aged 4 to 18 years with abdominal pain who had OC (defined as fecal impaction in abdominal X ray) were studied. Demographic and clinical data including age, sex, body weight, height, abdominal pain duration, abdominal pain rate and fecal odor were registered. They were randomly assigned to receive PEG (1gr/kg) or Lactulose (1cc/kg) for at least two weeks. All patients were reevaluated by pain measurement scale after at least two weeks of treatment. Results: It is indicated that the efficacy of PEG for reducing abdominal pain in OC was 48% while it was 37% for Lactulose. This study indicated that this efficacy is not affected significantly by sex and fecal odor, however this efficacy is influenced by age, body weight, abdominal pain duration and abdominal pain rate for both PEG and Lactulose. Conclusion: It could be concluded that PEG is a more efficient drug for treating abdominal pain in occult constipation than Lactulose and its optimum effect can be achieved in elder patients with more severe abdominal pain.

Introducción y objetivo: El dolor abdominal funcional (FAP) es una de las principales molestias gastrointestinales en la infancia. Los estudios han informado que el estreñimiento oculto (OC) es una de las principales causas de dolor abdominal. Investigaciones recientes han propuesto laxantes como objetivos terapéuticos potentes para el dolor abdominal en pacientes con OC. Sin embargo, ningún estudio ha comparado el efecto del polietilenglicol (PEG) y la lactulosa sobre el estreñimiento oculto. Materiales y métodos: Se estudiaron 51 pacientes de 4 a 18 años con dolor abdominal que tenían OC (definida como impactación fecal en rayos X abdominales). Se registraron datos demográficos y clínicos que incluyen edad, sexo, peso corporal, altura, duración del dolor abdominal, tasa de dolor abdominal y olor fecal. Fueron asignados aleatoriamente para recibir PEG (1 gr/kg) o lactulosa (1 cc/kg) durante al menos dos semanas. Todos los pacientes fueron reevaluados por la escala de medición del dolor después de al menos dos semanas de tratamiento. Resultados: Se indica que la eficacia de PEG para reducir el dolor abdominal en OC fue del 48% mientras que fue del 37% para la lactulosa. Este estudio indicó que esta eficacia no se ve afectada significativamente por el sexo y el olor fecal, sin embargo, esta eficacia está influenciada por la edad, el peso corporal, la duración del dolor abdominal y la tasa de dolor abdominal tanto para PEG como para lactulosa. Conclusión: Se podría concluir que el PEG es un fármaco más eficaz para tratar el dolor abdominal en el estreñimiento oculto que la lactulosa y que su efecto óptimo se puede lograr en pacientes mayores con dolor abdominal más severo.Palabras clave: dolor abdominal, estreñimiento oculto, polietilenglicol, lactulosa.

Caracterização fisico-química de produto curado seco de carne ovina elaborado com lactulose como prebiótico / Physicochemical characterization of dry-cured lamb with lactulose as prebiotic

O objetivo desse trabalho foi acompanhar as alterações nas características físico-químicas de produto curado dessecado de carne ovina adicionado de lactulose ao longo de sua elaboração (0, 7, 21 e 30 dias). Foram necessários 30 dias para que os produtos perdessem cerca de 40% de peso. A umidade foi afetada (P<0,05) apenas pelo tempo de processamento, atingindo valores finais de 47,60%. Em relação ao pH, houve efeito significativo (p<0,05) nos tempos e nos tratamentos analisados ao longo do processo. A presença de lactulose não afetou na produção de ácido lático e nem na Atividade de água. Foi possível desenvolver e caracterizar um produto de carne ovina adicionado de Prebiótico com as mesmas características em relação tratamento controle atendendo a legislação Brasileira.

Double blinded randomized clinical trial to assess the effectiveness of several preparations for colonoscopy / Ensaio clínico randomizado duplo cego para avaliar a eficácia de várias preparações para colonoscopia

ABSTRACT Introduction: Colonoscopy is the screening gold standard to investigate several conditions in the colon. The excellence of preparation is a determining factor for a quality colonoscopy. Objective: Compare the quality of colon preparations for colonoscopy with different kinds of laxative medications in a public hospital of Belo Horizonte, Brazil. Method: A prospective double blind randomized clinical trial was conducted from June 2016 to March 2017. A total of 117 Patients were randomised in four groups to receive a type of preparation (Sodium picosulfate, Mannitol, Lactitol, Lactulose). The patients answered a questionnaire and peripheral blood samples were collected before and after the preparation.The quality of the cleansing was accessed according to the Boston Bowel Preparation Scale. Results: 99.1% of patients have taken the recommended dose and 79.5% reported a good tolerability. Endoscopists performed complete colonoscopy in 89.7%, with an polipectomy rate of 47%. The total effectiveness rate of the solutions were 88%. There were no statistically significant differences between groups (p = 0.271). Regarding the laboratory parameters, differences were seen in the pre- and post-test values of sodium, chlorine and creatinine but without exceeding reference values. Conclusion: The four preparations were effective for colon cleansing, with good acceptance, differing only as for costs.

RESUMO Introdução: a colonoscopia é o padrão ouro de triagem para pesquisa de várias doenças colônicas. A excelência de preparação é um fator determinante para uma colonoscopia de qualidade. Objetivo: Comparar a qualidade das preparações do cólon para colonoscopia com diferentes tipos de medicamentos laxantes em um hospital público de Belo Horizonte, Brasil. Método: Foi realizado um ensaio clínico randomizado duplo cego prospectivo de junho de 2016 a março de 2017. Um total de 117 pacientes foi randomizado em quatro grupos para receber um tipo de preparação (picossulfato sódico, manitol, lacticol, lactulose). Os pacientes responderam a um questionário e amostras de sangue periférico foram coletadas antes e depois da preparação. A qualidade da limpeza foi acessada de acordo com a Boston Bowel Preparation Scale. Resultados: 99,1% dos pacientes tomaram a dose recomendada e 79,5% relataram boa tolerabilidade. Os endoscopistas realizaram colonoscopia completa em 89,7%, com taxa de polipectomia de 47%. A taxa de eficácia total das soluções foi de 88%. Não houve diferenças estatisticamente significantes entre os grupos (p = 0,271). Em relação aos parâmetros laboratoriais, foram observadas diferenças nos valores pré e pós-teste de sódio, cloro e creatinina, mas sem exceder os valores de referência. Conclusão: As quatro preparações foram eficazes para limpeza do cólon, com boa aceitação, diferindo apenas quanto aos custos.

Intestinal fructose malabsorption is associated with increased lactulose fermentation in the intestinal lumen / Má absorção intestinal de frutose associa-se com maior fermentação de lactulose na luz intestinal

Abstract Objective: To study fructose malabsorption in children and adolescents with abdominal pain associated with functional gastrointestinal disorders. As an additional objective, the association between intestinal fructose malabsorption and food intake, including the estimated fructose consumption, weight, height, and lactulose fermentability were also studied. Methods: The study included 31 patients with abdominal pain (11 with functional dyspepsia, 10 with irritable bowel syndrome, and 10 with functional abdominal pain). The hydrogen breath test was used to investigate fructose malabsorption and lactulose fermentation in the intestinal lumen. Food consumption was assessed by food registry. Weight and height were measured. Results: Fructose malabsorption was characterized in 21 (67.7%) patients (nine with irritable bowel syndrome, seven with functional abdominal pain, and five with functional dyspepsia). Intolerance after fructose administration was observed in six (28.6%) of the 21 patients with fructose malabsorption. Fructose malabsorption was associated with higher (p < 0.05) hydrogen production after lactulose ingestion, higher (p < 0.05) energy and carbohydrate consumption, and higher (p < 0.05) body mass index z-score value for age. Median estimates of daily fructose intake by patients with and without fructose malabsorption were, respectively, 16.1 and 10.5 g/day (p = 0.087). Conclusion: Fructose malabsorption is associated with increased lactulose fermentability in the intestinal lumen. Body mass index was higher in patients with fructose malabsorption.

Resumo Objetivo: Pesquisar a má absorção de frutose em crianças e adolescentes com dor abdominal associada com distúrbios funcionais gastrintestinais. Como objetivo adicional, estudou-se a relação entre a má absorção intestinal de frutose e a ingestão alimentar, inclusive a estimativa de consumo de frutose, o peso e a estatura dos pacientes e a capacidade de fermentação de lactulose. Métodos: Foram incluídos 31 pacientes com dor abdominal (11 com dispepsia funcional, 10 com síndrome do intestino irritável e 10 com dor abdominal funcional). O teste de hidrogênio no ar expirado foi usado para pesquisar a má absorção de frutose e a fermentação de lactulose na luz intestinal. O consumo alimentar foi avaliado por registro alimentar. Foram mensurados também o peso e a estatura dos pacientes. Resultados: Má absorção de frutose foi caracterizada em 21 (67,7%) pacientes (nove com síndrome do intestino irritável, sete com dor abdominal funcional e cinco com dispepsia funcional). Intolerância após administração de frutose foi observada em seis (28,6%) dos 21 pacientes com má absorção de frutose. Má absorção de frutose associou-se com maior produção de hidrogênio após ingestão de lactulose (p < 0,05), maior consumo de energia e carboidratos (p < 0,05) e maior valor de escore z de IMC para a idade (p < 0,05). As medianas da estimativa de ingestão diária de frutose pelos pacientes com e sem má absorção de frutose foram, respectivamente, 16,1 e 10,5 g/dia (p = 0,087). Conclusão: Má absorção de frutose associa-se com maior capacidade de fermentação de lactulose na luz intestinal. O índice de massa corporal foi maior nos pacientes com má absorção de frutose.

El impacto del tratamiento de la encefalopatía hepática mínima en el pronóstico a largo plazo / The impact of minimal hepatic encephalopathy treatment in long-term prognosis

La encefalopatía hepática mínima (EHm) afecta del 30% al 50% de los pacientes cirróticos. Su detección es esencial por su relación con la encefalopatía hepática clínica, la alteración de la habilidad para conducir, el mayor riesgo de caídas, la alteración de la calidad de vida, la progresión más acelerada de la cirrosis y la supervivencia. A pesar de la información fidedigna de su relevancia clínica, pronóstica y social, la detección de EHm no está generalizada en la práctica clínica. El espectro de la encefalopatía hepática engloba diversas alteraciones de las funciones cerebrales, por lo que se requiere realizar más de un test para su diagnóstico. Además, las alteraciones iniciales difieren de un paciente a otro. Esto ha dificultado el desarrollo de una estrategia diagnóstica universal. Como resultado, no disponemos de datos suficientes para generar recomendaciones basadas en la evidencia del impacto del tratamiento de la EHm en la calidad de vida y la supervivencia, así como de su rentabilidad. Por lo tanto, las guías clínicas actuales sugieren que se evalúe la EHm cuando se afecta la calidad de vida de los pacientes, ya que no se conocen las consecuencias del tamizaje. Las terapias reductoras de amonio se consideran la piedra angular del tratamiento de la EHm. Los disacáridos no absorbibles, la rifaximina y, más recientemente, los probióticos, han mostrado efectos beneficiosos. Se necesitan más ensayos controlados con placebo para evaluar la eficacia, seguridad y rentabilidad de los regímenes de tratamiento disponibles para evaluar el impacto del tratamiento de la EHm en el pronóstico a largo plazo de estos pacientes.

Minimal hepatic encephalopathy (MHE) affects up to 30-50% of cirrhotic patients. The detection of MHE is essential because of its relationship with overt hepatic encephalopathy, impairment of motor vehicle driving abilities, higher risk of falls, quality of life impairment, faster cirrhosis progression and survival. Despite the robust evidence regarding its clinical, prognostic and social relevance, MHE testing is not widespread in routine clinical care. Hepatic encephalopathy spectrum covers various alterations in complex brain functions, requiring more than one test to be quantified. In addition, initial disturbances differ from one patient to another. All this has made it difficult to develop a universal diagnostic strategy. As a consequence, there is a lack of available robust data in the literature to generate evidence-based recommendations related to the impact of MHE treatment on quality of life and survival of these patients, as well as on cost-effectiveness. Therefore, current clinical guidelines suggest MHE testing only when patients have problems with their quality of life, since consequences of the screening procedure are still unclear. Ammonia lowering therapies have been considered the cornerstone of MHE treatment. Beneficial effects of non-absorbable disaccharides (lactulose or lactitol), rifaximin and more recently, probiotics have been reported. Further placebo-controlled trials are needed to assess the efficacy, safety, and cost-effectiveness of available treatment regimes to evaluate the impact of MHE treatment on the long-term prognosis of these patients.

Minimal Hepatic Encephalopathy in Cirrhosis- How Long to Treat?

Abstract: Introduction. Minimal hepatic encephalopathy (MHE) can reverse after short-term treatment. However, relapse rate of MHE after stopping treatment has not been studied so far. We aimed to evaluate long-term (9 months) efficacy of a short-term (3 months) treatment of MHE with lactulose/rifaximin, for maintenance of remission from MHE. Material and methods. In this prospective study, consecutive patients with cirrhosis and MHE were treated with lactulose/rifaximin for 3 months. After treatment, they were followed up for 6 months. Psychometric testing for diagnosis of MHE was performed at baseline, 3 months and 9 months. Results. Of the 527 patients screened, 351 were found eligible and tested for MHE. Out of these, 112 (31.9%) patients had MHE (mean age 55.3 years; 75% males). They were randomized to receive Rifaximin (n = 57; 1,200 mg/day) or Lactulose (n = 55; 30-120 mL/day) for three months. At 3 months, 73.7% (42/57) patients in Rifaximin group experienced MHE reversal compared to 69.1% (38/55) in Lactulose group (p = 0.677). Six months after stopping treatment, 47.6% (20/42) in rifaximin group and 42.1% (16/38) patients in lactulose group experienced MHE relapse (p = 0.274). The overt hepatic encephalopathy development rate (7.1% vs. 7.9%) and mortality rate (0.23% vs. 0%) were similar in both groups. The Child-Turcotte-Pugh score and model for end stage liver disease (MELD) scores of patients who had MHE relapse were higher compared to those who didn’t. On multivariate regression analysis, MELD score was an independent predictor of MHE relapse. Conclusion. Of the patients who became MHE negative after short-term (3 months) treatment with rifaximin/lactulose, almost 50% had a relapse of MHE at 6 months follow-up.

Eficacia y seguridad de rifaximina alfa en pacientes con encefalopatia hepatica refractaria al uso de lactulosa / Efficacy and safety of rifaximin alfa in patients with hepatic encephalopathy refractory to the use of lactulose

INTRODUCCIÓN: Antecedentes: El presente dictamen responde a la solicitud de evaluación del uso del petitorio de Rifaximina alfa en pacientes con encefalopatia hepática refractaria al uso de lactulosa. Aspectos Generales: Se estima que aproximadamente 5.5 millones de personas en los Estados Unidos sufren de cirrosis hepática, una causa de movilidad y mortalidad tanto en este país como en el mundo. La encefalopatia hepática o encefalopatía portosistemica constituye una complicación de la cirrosis hepática y falla de la función neuropsiquiátrica asociada con falla en la función hepática. A pesar que la condición es frecuentemente diagnosticada aún no existe un claro entendimiento de la patogénesis. Sin embargo, se estipula que se puede deber a un incremiento en las concentraciones de amoniaco en vista que el higado ya no es capaz de eliminar las toxinas de la sangre causando así toxicidad en el cerebro. Puede presentarse como episodios agudos o crónicamente a largo plazo. Tecnología Sanitaria de Interés: La Rifaximina alfa es un agente antimicrobiano con un amplio espectro de acción sobre Bacterias Gram-positivas y Gram- negativas, tanto aerobias como anaerobais. La característica de Rifaximina alfa es su forma polimorfa alfa y su escasa absorción en el tracto gastrointestinal (inferior a 1%), lo cual favorece la concentración del fármaco en el intestino y sobre todo, en las heces en forma activa. METODOLOGÍA: Estrategia de Búsqueda: Se llevó a cabo una búsqueda sistemática de la literatura con respecto a la eficacia y seguridad de Rifaximina alfa para el tratamiento de pacientes con encefalopatía hepática con resistencia (falla) al tratamiento estándar con lactulosa. La búsqueda se inicio revisando la información sobre el uso del medicamento de acuerdo con entidades reguladoras com la Food and Drug Administration (FDA), la European Medicines Agency (EMA) y la Dirección General de Medicamentos y Drogas (DIGEMID). Posteriomente se buscaron Guías de Práctica Clínica a través de los metabuscadores: Translating Research into Practice (TRIPDATABASE), National Library of Medicine (Pubmed-Medline), The National Guuideline of Clearinghouse, y Health Systems Evidence. Finalmente. se realizó una búsqueda dentro de la información generada por grupos internacionales que realizan revisiones sistemáticas, evaluación de tecnologías sanitarias y guías de práctica clínica. RESULTADOS: Sinopsis de la Evidencia: En la presente sinopsis se describe la evidencia disponible que sustenta la eficacia y seguridad de Rifaximina alfa para el tratamiento de pacientes con encefalopatia hgepática refractarios al tratamiento estándar con lactulosa. CONCLUSIONES: A la fecha, no se ha evaluado la eficacia y seguridad de Rifazimina alfa como monoterapia ni en pacientes refractarios a lactulosa, por lo que la evidencia encontrada responde la pregunta PICO de manera indirecta. Actualmente no existe alternativa de tratamiento a lactulosa en el Petitorio Farmacológico de EsSalud, por lo que es necesario contar con una alternativa de tratamiento para así evitar el deterioro de la calidad de vida del paciente, dadas las limitaciones en las funciones cognitiva y psicomotriz a la que la enfermedad conlleva. El Instituto de Evaluacioón de Tecnologías en Salud e Investigación-IETSI, aprueba el uso de Rifaximina alfa en pacientes con encefalopatía hepática refractaria al uso de lactulosa. El presente Dicatamen Preliminar tiene una vigencia de dos años a partir de su fecha de publicación.

Efficacy of lactulose in the prophylaxis of hepatic encephalopathy in cirrhotic patients presenting gastrointestinal bleeding / Eficácia da lactulose na profilaxia de encefalopatia hepática em pacientes cirróticos apresentando hemorragia digestiva

SUMMARY Introduction: Hepatic encephalopathy (HE) is a bad prognostic factor in patients with liver cirrhosis and its incidence is associated with several triggering factors being the most prevalent gastrointestinal bleeding. Lactulose, despite its questionable efficacy in the literature, is considered a first line treatment in patients with HE. Objective: To evaluate the effectiveness of lactulose in preventing HE in cirrhotic patients with gastrointestinal bleeding. Method: A systematic review of the literature using the Medline scientific database. Only randomized controlled clinical trials evaluating the efficacy of lactulose for HE prophylaxis in cirrhotic patients with gastrointestinal bleeding were included. Results: The incidence of HE in the intervention group was 7%, while the control group was 26% (p=0.01). There was no significant difference in the incidence of mortality in the group treated with lactulose compared to the group that was not treated (p=0.48). Conclusion: Administering lactulose to cirrhotic patients with upper gastrointestinal bleeding reduces the incidence of hepatic encephalopathy.

RSUMO Introdução: encefalopatia hepática (EH) é fator de mau prognóstico no paciente com cirrose hepática e sua incidência está associada a vários fatores desencadeantes, sendo a hemorragia digestiva o mais prevalente. A lactulose, apesar de apresentar eficácia discutível na literatura, é considerada tratamento de primeira linha em pacientes com EH. Objetivo: avaliar a eficácia da lactulose na prevenção de EH em pacientes cirróticos apresentando hemorragia digestiva. Método: realizou-se revisão sistemática da literatura pela base de dados Medline. Foram incluídos apenas ensaios clínicos controlados e randomizados que avaliaram a eficácia da lactulose na profilaxia de EH em pacientes cirróticos com hemorragia digestiva. Resultados: a incidência de EH no grupo intervenção foi de 7% enquanto no grupo controle foi de 26% (p=0,01). Não houve diferença significante na incidência de mortalidade entre o grupo que recebeu lactulose e o que não recebeu (p=0,48). Conclusão: a administração de lactulose em pacientes cirróticos apresentando hemorragia digestiva alta diminui a incidência de encefalopatia hepática.

Dermatite associada à incontinência: estudo de coorte em pacientes críticos / Dermatitis asociada con incontinencia: estudio de cohorte en pacientes críticos / Incontinence-associated dermatitis: a cohort study in critically ill patients

RESUMO Objetivos Estimar incidência, determinar fatores de risco e propor modelo de predição de risco para desenvolvimento de dermatite associada a incontinência em pacientes adultos críticos. Método Trata-se de um estudo de coorte concorrente realizado com 157 pacientes críticos. A coleta de dados foi conduzida diariamente entre fevereiro e julho de 2015 em hospital público e de ensino de Belo Horizonte, MG. Os dados foram lançados em banco de dados, submetidos a análise descritiva de sobrevida e multivariada. Resultados Obteve-se uma incidência global de 20,4%. Foram encontrados 19 fatores de risco que apresentaram associação significativa com o problema. As variáveis encontradas no modelo de predição de risco foram: sexo masculino, trauma, uso de hipnótico/sedativos, lactulona, suporte nutricional, fezes pastosas e queixa de ardência (local). Conclusão Os resultados mostraram que a dermatite é um achado clínico comum em pacientes adultos críticos e merece atenção especial para maior qualidade da assistência de enfermagem.

RESUMEN Objetivos Estimar incidencia, determinar factores de riesgo y proponer modelo de predicción de riesgo para el desarrollo de la dermatitis asociada a la incontinencia en pacientes adultos críticos. Método Se trata de un estudio de cohorte concurrente de 157 pacientes críticamente enfermos. La recolección de datos se realizó diariamente entre febrero y julio de 2015, en un hospital público y de enseñanza de Belo Horizonte-MG. Los datos se introdujeron en la base de datos, sometidos a análisis descriptivo, de supervivencia y multivariada. Resultados Se obtuvo una incidencia global del 20,4%. Se encontraron 19 factores de riesgo asociados significativamente con el problema. Las variables identificadas en el modelo de predicción de riesgo fueron: sexo masculino, trauma, uso de hipnóticos/sedantes, lactulona, soporte nutricional, heces sueltas y queja de ardor (local). Conclusión Los resultados mostraron que la dermatitis es un hallazgo clínico frecuente en pacientes adultos críticos y merece una atención especial para una mayor calidad de los cuidados de enfermería.

ABSTRACT Objectives Estimate incidence, determine risk factors and propose a prediction model for the development of incontinence- associated dermatitis critically ill adult patients. Method Concurrent cohort study with 157 critically ill patients. Data collection was daily performed between February and July 2015, at a public teaching hospital of Belo Horizonte, Minas Gerais. Data was entered in a database and subjected to descriptive, survival and multivariate analysis. Results An overall incidence of 20.4% was obtained. Nineteen (19) risk factors significantly associated with the disorder were found. The variables identified in the risk prediction model were male, trauma, use of hypnotics/sedatives, lactulose, nutritional support, loose stools and complaints of burning. Conclusion The results showed that dermatitis is a common clinical finding in critically ill adult patients and requires special attention from the nursing staff.

Intestinal permeability in leukemic patients prior to chemotherapy

Objective: The objective of this study was to evaluate the intestinal barrier function in leukemia patients before the start of the chemotherapy with an intestinal permeability test using lactulose and mannitol as markers. Methods: The study enrolled 20 patients diagnosed with leukemia (acute and chronic). Ten healthy volunteers were also submitted to the test as a control group. Results: The median lactulose/mannitol ratio was 0.019 for the Leukemia Patient Group, whereas in healthy controls the median was 0.009 (p-value = 0.244). The median lactulose/mannitol ratio in acute leukemia patients was 0.034 giving a p-value of 0.069 when compared to healthy controls. This same comparison was made between acute myeloid leukemia patients and healthy controls with a p-value of 0.149. There was no significant difference in the intestinal permeability between acute and chronic leukemia patients (p-value = 0.098). Conclusion: The intestinal barrier function measured using the intestinal permeability test was similar in leukemic patients overall and healthy controls, but a tendency toward a different pattern was found in the intestinal barrier function of acute leukemia patients...

Efeito da lactulose sobre os teores séricos de ureia, creatinina, cálcio e fósforo em cães não azotêmicos / Effect of lactulose on serum urea, creatinine, calcium and phosphorus in non-azothemic dogs

The present study evaluated serum levels of urea, creatinine, calcium and phosphorus in non-azothemic dogs by continued use of lactulose orally. Serum levels of urea, creatinine, calcium and phosphorus were determined in Beagle dogs, clinically healthy and without biochemical changes (non-azothemic), undergoing oral treatment with lactulose (n = 6), for a period of 30 days. The prebiotic showed no significant lowering effect on serum urea and creatinine, but the values of calcium and phosphorus, as well as their relation, were modified with reduced serum phosphorus levels in animals treated with lactulose compared to controls, with a significant difference...

Double-blind prospective randomized study comparing polyethylene glycol to lactulose for bowel preparation in colonoscopy / Estudo prospectivo randomizado duplo-cego comparando polietilenoglicol com lactulose para preparo de colon em colonoscopia

Background: Colonoscopy is the most frequent exam used to evaluate colonic mucosa, allowing the diagnosis and treatment of many diseases. The appropriate bowel preparation is indispensable for the realization of colonoscopy. Therefore, it is necessary the use of laxative medications, preferentially by oral administration. Aim: To compare two medications used in bowel preparation in adult patients going to ambulatory colonoscopy and to analyze the patients' profile. Methods: A double-blind prospective study with 200 patients, randomized in two groups: one that received polyethilene glycol and another that received lactulose. The patients answered to questionnaires to data compilation, as tolerance, symptoms and complications related to preparation. Besides, it was also evaluated the prepare efficacy related to the presence of fecal residue. Results: Intestinal habit alterations and abdominal pain were the main reasons to realize the exams and hypertension was the most prevalent comorbidity. Ten percent of the ones who received lactulose didn't get to finish the preparation and 50% considered the taste "bad, but tolerable". The most common subjective symptom after the medication was nausea, especially after lactulose. During the exam, most of the patients who used lactulose had a "light discomfort" and the ones who used polyethilene glycol considered the discomfort as "tolerable". The quality of the preparation was good in 75%, undependable of the medication that was used. Conclusion : Polyethilene glycol was more tolerable when compared to lactulose, without difference on the quality of the preparation. .

Racional - A colonoscopia é o exame mais utilizado atualmente para avaliação da mucosa colônica, permitindo diagnóstico e tratamento de diversas doenças. O preparo de cólon adequado é imprescindível para a realização do exame. Para tanto, é necessária a utilização de laxantes, cuja via preferencial de preparo é a oral. Objetivo - Comparar duas soluções para preparo de cólon nos pacientes adultos a serem submetidos à colonoscopia em regime ambulatorial e o perfil destes pacientes. Métodos - Estudo prospectivo duplo-cego com 200 pacientes distribuídos aleatoriamente em dois grupos: um que recebeu dose padrão de polietilenoglicol e o outro que recebeu dose padrão de lactulose. Os pacientes responderam a questionários para compilação de dados, como tolerância, sintomas e complicações relacionadas ao preparo. Além disso, foi avaliada também a eficácia do preparo com relação à presença de resíduos fecais. Resultados - Alteração do hábito intestinal e dor abdominal foram os principais motivos para o exame, sendo que hipertensão a comorbidade mais prevalente. Dez por cento dos que receberam lactulona não conseguiram completar o preparo e 50% consideraram o gosto do preparo "ruim, mas tolerável". O sintoma subjetivo mais comum após o preparo foi náusea, principalmente após a lactulona. Durante o exame, a maioria dos usuários da lactulona teve desconforto "leve", sendo que os que usaram polietilenoglicol consideraram o desconforto como "tolerável". A qualidade do preparo foi boa em 75%, independentemente do preparo utilizado. Conclusão - O polietilenoglicol apresentou melhor tolerância quando comparado à lactulona, não havendo diferença na qualidade do preparo. .