Drug-induced Liver Injury in Latin America: 10-year Experience of the Latin American DILI (LATINDILI) Network.

BACKGROUND & AIMS: Latin America is a region of great interest for studying the clinical presentation of idiosyncratic drug-induced liver injury (DILI). A comprehensive analysis of patients enrolled into the LATINDILI Network over a decade is presented. METHODS: Demographics, clinical presentation, histological findings and outcome of prospectively recruited DILI cases in the LATINDILI Network were analyzed. Suspected culprit drugs were classified according to the Anatomical Therapeutic Chemical classification. Causality was assessed using the Roussel Uclaf Causality Assessment Method (RUCAM) scale. RESULTS: Overall, 468 idiosyncratic DILI cases were analyzed (62% women; mean age, 49 years). Hepatocellular injury predominated (62%); jaundice was present in 60% of patients, and 42% were hospitalized. Of the cases, 4.1% had a fatal outcome, and 24 patients (12%) developed chronic DILI. The most common drug classes were systemic anti-infectives (31%), musculoskeletal agents (12%), antineoplastic and immunomodulating agents (11%), and herbal and dietary supplements (9%). Notably, none of the patients with DILI due to antibacterials or immunosuppressants had a fatal outcome. In fact, Hy's law showed to have drug-specific predictive value, with anti-tuberculosis drugs, nimesulide, and herbal and dietary supplements associated with the worst outcome, whereas DILI caused by amoxicillin-clavulanate, nitrofurantoin, and diclofenac, which fulfilled Hy's law, did not have a fatal outcome. CONCLUSION: Features of DILI in Latin America are comparable to other prospective registries. However, the pattern of drugs responsible for DILI differs. An increasing incidence of herbal and dietary supplements, with high mortality rate, and likewise, nimesulide and nitrofurantoin, was noted. Thus, public health policies should raise awareness of the potential adverse effects of these compounds.

OXR1 maintains the retromer to delay brain aging under dietary restriction.

Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd/OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids. Loss of mtd/OXR1 destabilized the retromer, causing improper protein trafficking and endolysosomal defects. Overexpression of retromer genes or pharmacological restabilization with R55 rescued lifespan and neurodegeneration in mtd-deficient flies and endolysosomal defects in fibroblasts from patients with lethal loss-of-function of OXR1 variants. Multi-omic analyses in flies and humans showed that decreased Mtd/OXR1 is associated with aging and neurological diseases. mtd/OXR1 overexpression rescued age-related visual decline and tauopathy in a fly model. Hence, OXR1 plays a conserved role in preserving retromer function and is critical for neuronal health and longevity.

Pancreatitis aguda como manifestación atípica de chikungunya. Reporte de un caso / Acute pancreatitis as an chikungunya atypical manifestation. A case report

La fiebre chikungunya es una enfermedad tropical transmitida a los humanos mediante la picadura del mosquito Aedes aegypti y Aedes albopictus. Se manifiesta por fiebre alta, cefalea, mialgias y artralgias. Generalmente tiene un comportamiento benigno; sin embargo, se han reportado casos con manifestaciones atípicas y mortales. Es una virosis emergente del siglo XXI que en el Ecuador se convirtió en una epidemia en el año 2014. Reportamos un caso de una paciente de sexo femenino, 52 años de edad, residente en Quito (Ecuador) que presenta dolor abdominal, dolor torácico, artralgias, mialgias y alza térmica. Fue tratada por pancreatitis aguda de origen a determinar; no obstante, por los antecedentes epidemiológicos y el cuadro sintomático sugerente, se solicitó IgM (inmunoglobulina M) para chikungunya que fue positiva. Se la trató mediante hidratación y analgésicos; tuvo una adecuada respuesta sintomática.

Chikungunya fever is a tropical disease transmitted to humans by the mosquito bite Aedes aegypti and Aedes albopictus. It is characterized clinically by causing high fever, headache, myalgias and arthralgias; usually has a benign behavior, but cases with atypical manifestations that produce mortality are reported. It is an emerging virus in the 21st century. We report a case of a 52-year-old female patient living in Quito, Ecuador, with abdominal pain, chest pain, arthralgia, myalgias and fever. It was treated by acute pancreatitis of origin to determine, however by epidemiological antecedents and suggestive clinical, we decided to request IgM for chikungunya which was positive. The patient received treatment with hydration and analgesia, with adequate clinical response