Role of Mitochondria in Inflammatory Bowel Diseases: A Systematic Review.

Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria are involved in a much higher number of cellular processes. Mitochondria are the home of key metabolic pathways like the tricarboxylic acid cycle and ß-oxidation of fatty acids, as well as biosynthetic pathways of key products like nucleotides and amino acids, the control of the redox balance of the cell and detoxifying the cell from H2S and NH3. This plethora of critical functions within the cell is the reason mitochondrial function is involved in several complex disorders (apart from pure mitochondrial disorders), among them inflammatory bowel diseases (IBD). IBD are a group of chronic, inflammatory disorders of the gut, mainly composed of ulcerative colitis and Crohn's disease. In this review, we present the current knowledge regarding the impact of mitochondrial dysfunction in the context of IBD. The role of mitochondria in both intestinal mucosa and immune cell populations are discussed, as well as the role of mitochondrial function in mechanisms like mucosal repair, the microbiota- and brain-gut axes and the development of colitis-associated colorectal cancer.

Long-Term Outcomes of Intravenous Ustekinumab Maintenance Treatment in Patients With Loss of Response to Subcutaneous Dosing.

BACKGROUND: Ustekinumab (UST) is commonly used to treat Crohn's disease and ulcerative colitis. However, some patients may experience diminishing response or require increased dosage. Intravenous (IV) UST maintenance is explored as a solution. OBJECTIVES: We sought to evaluate IV UST maintenance effectiveness and safety in inflammatory bowel disease patients with partial or lost subcutaneous UST response. METHODS: This was a multicenter retrospective study of inflammatory bowel disease patients on IV UST maintenance. Clinical response and remission at weeks 12 and 52, defined as Harvey-Bradshaw Index ≤4 for Crohn's disease or partial Mayo score ≤2 for ulcerative colitis. Objective markers reduction (fecal calprotectin, C-reactive protein), UST trough levels pre- and post-IV maintenance, and adverse events were assessed. RESULTS: A total of 59 patients were included. Clinical remission at weeks 12 and 52 achieved by 47.5% and 64.3% respectively. 96.6% continued IV UST at follow-up. UST serum levels quadrupled. No adverse events reported. CONCLUSIONS: IV UST maintenance effectively sustained remission in most patients at 52 weeks.

When patients lose response to subcutaneous ustekinumab, strategies include reinduction, interval shortening, and less explored intravenous maintenance. Its high rescue rate and safety profile make it a valuable option for managing active inflammatory bowel disease.

Causality assessment methods in drug induced liver injury: strengths and weaknesses.

Diagnosis of drug-induced liver injury (DILI) remains a challenge and eagerly awaits the development of reliable hepatotoxicity biomarkers. Several methods have been developed in order to facilitate hepatotoxicity causality assessments. These methods can be divided into three categories: (1) expert judgement, (2) probabilistic approaches, and (3) algorithms or scales. The last category is further divided into general and liver-specific scales. The Council for International Organizations of Medical Sciences (CIOMS) scale, also referred to as the Roussel Uclaf Causality Assessment Method (RUCAM), although cumbersome and difficult to apply by physicians not acquainted with DILI, is used by many expert hepatologists, researchers, and regulatory authorities to assess the probability of suspected causal agents. However, several limitations of this scale have been brought to light, indicating that a number of adjustments are needed. This review is a detailed timely criticism to alert the readers of the limitations and give insight into what would be needed to improve the scale. Instructions on how to approach DILI diagnosis in practice are provided, using CIOMS as an aid to emphasize the topics to be addressed when assessing DILI cases. Amendments of the CIOMS scale in the form of applying authoritative evidence-based criteria, a simplified scoring system and appropriate weighting given to individual parameters based on statistical evaluations with large databases will provide wider applicability in the clinical setting.

[Safety of conservative treatment of gastric perforation due to fish bone ingestion]. / Seguridad del tratamiento conservador de la perforación gástrica por espinas de pescado.

Intake of foreign bodies is the second most frequent indication for urgent upper gastrointestinal endoscopy. Once in the stomach, foreign bodies are usually spontaneously eliminated. However, a small percentage of large or sharp objects become stuck in the gastrointestinal mucosa. Fish bones represent a substantial number of ingested foreign bodies. We present two cases of fish bone intake producing gastric perforation satisfactorily resolved with endoscopy. Perforation is considered an absolute spcontraindication for upper and lower gastrointestinal endoscopy. Cases such as those reported herein indicate that the decision to perform endoscopic treatment should always be individualized since punctiform perforations - especially if associated with a parietal and peritoneal inflammatory reaction that helps to close the perforation spontaneously - can be treated non-surgically.

Assessment of drug-induced hepatotoxicity in clinical practice: a challenge for gastroenterologists.

Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be fine-tuned as further information is collected.

Hepatitis aguda en una paciente con gripe A: ¿casualidad o causalidad? / Acute hepatitis in a woman with influenza A virus: Cause or coincidence?

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Hepatotoxicidad por productos de herboristería / Hepatotoxicity by herbal products

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Seguridad del tratamiento conservador de la perforación gástrica por espinas de pescado / Safety of conservative treatment of gastric perforation due to fish bone ingestion

La ingesta de cuerpos extraños representa la segunda indicación en frecuencia para la realización de una endoscopia digestiva alta urgente. Una vez que pasan al estómago suelen expulsarse de forma espontánea, si bien un porcentaje bajo de éstos queda enclavado en la mucosa gastrointestinal por ser afilados o de gran tamaño.Las espinas de pescado son un importante número de los cuerpos extraños ingeridos.Se presentan 2 casos en que la ingesta de una espina de pescado produjo una perforación gástrica que se resolvió satisfactoriamente de forma endoscópica.La perforación se considera una contraindicación absoluta para realizar endoscopias, tanto altas como bajas, si bien casos como éstos enseñan a individualizar siempre la decisión de realizar tratamientos endoscópicos, ya que perforaciones puntiformes, sobre todo si se asocian a reacción inflamatoria parietal y peritoneal que ayude a cerrar la perforación de forma espontánea, pueden tratarse sin recurrir a cirugía(AU)

Intake of foreign bodies is the second most frequent indication for urgent upper gastrointestinal endoscopy. Once in the stomach, foreign bodies are usually spontaneously eliminated. However, a small percentage of large or sharp objects become stuck in the gastrointestinal mucosa.Fish bones represent a substantial number of ingested foreign bodies. We present two cases of fish bone intake producing gastric perforation satisfactorily resolved with endoscopy.Perforation is considered an absolute spcontraindication for upper and lower gastrointestinal endoscopy. Cases such as those reported herein indicate that the decision to perform endoscopic treatment should always be individualized since punctiform perforations – especially if associated with a parietal and peritoneal inflammatory reaction that helps to close the perforation spontaneously – can be treated non-surgically(AU)