Clinical and Preclinical Targeting of Oncogenic Pathways in PDAC: Targeted Therapeutic Approaches for the Deadliest Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. It is commonly diagnosed in advanced stages and therapeutic interventions are typically constrained to systemic chemotherapy, which yields only modest clinical outcomes. In this review, we examine recent developments in targeted therapy tailored to address distinct molecular pathway alteration required for PDAC. Our review delineates the principal signaling pathways and molecular mechanisms implicated in the initiation and progression of PDAC. Subsequently, we provide an overview of prevailing guidelines, ongoing investigations, and prospective research trajectories related to targeted therapeutic interventions, drawing insights from randomized clinical trials and other pertinent studies. This review focus on a comprehensive examination of preclinical and clinical data substantiating the efficacy of these therapeutic modalities, emphasizing the potential of combinatorial regimens and novel therapies to enhance the quality of life for individuals afflicted with PDAC. Lastly, the review delves into the contemporary application and ongoing research endeavors concerning targeted therapy for PDAC. This synthesis serves to bridge the molecular elucidation of PDAC with its clinical implications, the evolution of innovative therapeutic strategies, and the changing landscape of treatment approaches.

Exploring the chemical space of orally bioavailable PROTACs.

A principal challenge in the discovery of proteolysis targeting chimeras (PROTACs) as oral medications is their bioavailability. To facilitate drug design, it is therefore essential to identify the chemical space where orally bioavailable PROTACs are more likely to be situated. To this aim, we extracted structure-bioavailability insights from published data using traditional 2D descriptors, thereby shedding light on their potential and limitations as drug design tools. Subsequently, we describe cutting-edge experimental, computational and hybrid design strategies based on 3D descriptors, which show promise for enhancing the probability of discovering PROTACs with high oral bioavailability.

Andean soil-derived lignocellulolytic bacterial consortium as a source of novel taxa and putative plastic-active enzymes.

An easy and straightforward way to engineer microbial environmental communities is by setting up liquid enrichment cultures containing a specific substrate as the sole source of carbon. Here, we analyzed twenty single-contig high-quality metagenome-assembled genomes (MAGs) retrieved from a microbial consortium (T6) that was selected by the dilution-to-stimulation approach using Andean soil as inoculum and lignocellulose as a selection pressure. Based on genomic metrics (e.g., average nucleotide and amino acid identities) and phylogenomic analyses, 15 out of 20 MAGs were found to represent novel bacterial species, with one of those (MAG_26) belonging to a novel genus closely related to Caenibius spp. (Sphingomonadaceae). Following the rules and requirements of the SeqCode, we propose the name Andeanibacterium colombiense gen. nov., sp. nov. for this taxon. A subsequent functional annotation of all MAGs revealed that MAG_7 (Pseudobacter hemicellulosilyticus sp. nov.) contains 20, 19 and 16 predicted genes from carbohydrate-active enzymes families GH43, GH2 and GH92, respectively. Its lignocellulolytic gene profile resembles that of MAG_2 (the most abundant member) and MAG_3858, both of which belong to the Sphingobacteriaceae family. Using a database that contains experimentally verified plastic-active enzymes (PAZymes), twenty-seven putative bacterial polyethylene terephthalate (PET)-active enzymes (i.e., alpha/beta-fold hydrolases) were detected in all MAGs. A maximum of five putative PETases were found in MAG_3858, and two PETases were found to be encoded by A. colombiense. In conclusion, we demonstrate that lignocellulose-enriched liquid cultures coupled with genome-resolved metagenomics are suitable approaches to unveil the hidden bacterial diversity and its polymer-degrading potential in Andean soil ecosystems.

Engineering microbiomes to transform plastics.

The design and study of active microbial consortia able to degrade plastics represent an exciting area of research toward the development of bio-based alternatives to efficiently transform plastic waste. This forum article discusses concepts and mechanisms to inform emerging strategies for engineering microbiomes to transform plastics under controlled settings.

Acute complications in open/miss primary and revision thoracolumbar spine surgery: a descriptive study of the most common complications and treatment of choice.

PURPOSE: Main question The aim of this study is to describe and analyze the frequency of acute perioperative (intraoperatively and 30 days after) complications of open/MISS thoracolumbar spine surgery. Secondary questions A) Describe the treatment of choice for every kind of complication mentioned. B) Perform a bibliographic search and compare the complications described and their frequency with those studied in the manuscript. METHODS: A retrospective cohort of 816 patients undergoing spinal surgery over a two year period was analyzed. Acute complications of 59 patients are described whether those with a greater number of levels required longer periods of hospitalization. RESULTS: The frequency of acute complications was 7.2%. The most common was infection (2.7%), followed by dural tear (1.7%), and screw malpositioning (1%), which is consistent with the current literature. No statistically significant results were observed when comparing the mean length of hospital stay among patients operated on a greater number of levels compared to the rest (P: 0.344; 95% CI: -3.88-10.93). CONCLUSIONS: The subsidiary patient of spinal surgery is getting older and has more comorbidities, and therefore, has a higher risk of complications. Although there are models predicting the risk of complications, they are not used in routine clinical practice. It would be necessary to unify the main criteria and establish guidelines for risk detection and therapeutic algorithms based on new high-quality studies.

Size Exclusion Chromatography-Mass Photometry: A New Method for Adeno-Associated Virus Product Characterization.

Over the past decade, adeno-associated viruses (AAVs) have attained significant prominence in gene therapy and genome editing applications, necessitating the development of robust and precise methodologies to ensure the quality and purity of AAV products. Existing AAV characterization techniques have proven effective for the analysis of pure and homogeneous AAV samples. However, there is still a demand for a rapid and low-sample-consumption method suitable for the characterization of lower purity or heterogeneous AAV samples commonly encountered in AAV products. Addressing this challenge, we propose the SEC-MP method, which combines size exclusion chromatography (SEC) with mass photometry (MP). In this novel approach, SEC effectively separates monomeric AAV particles from impurities, while the UV detector determines the virus particle concentration. MP complements this process by estimating the fraction of fully packaged AAVs in the total population of AAV particles. This combined methodology enables accurate determination of the titer of effective, fully packaged AAVs in samples containing aggregates, incorrectly packaged AAVs with incomplete genomes, protein or DNA fragments, and other impurities. Our experimental results demonstrate that SEC-MP provides valuable guidance for sample quality control and subsequent applications in the field of AAV research.

Group I Alkoxides and Amylates as Highly Efficient Silicon-Nitrogen Heterodehydrocoupling Precatalysts for the Synthesis of Aminosilanes.

Group I alkoxides are highly active precatalysts in the heterodehydrocoupling of silanes and amines to afford aminosilane products. The broadly soluble and commercially available KOt Amyl was utilized as the benchmark precatalyst for this transformation. Challenging substrates such as anilines were found to readily couple primary, secondary, and tertiary silanes in high conversions (>90 %) after only 2 h at 40 °C. Traditionally challenging silanes such as Ph3 SiH were also easily coupled to simple primary and secondary amines under mild conditions, with reactivity that rivals many rare earth and transition-metal catalysts for this transformation. Preliminary evidence suggests the formation of hypercoordinated intermediates, but radicals were detected under catalytic conditions, indicating a mechanism that is rare for Si-N bond formation.

A random forest approach to explore how situational variables affect perceived exertion of elite youth soccer players.

The aim of this study was to explore how situational variables affect youth soccer players' perceived exertion (RPE) after official matches. Thirty-five elite youth male players (14.33 ± 0.86 years; 173.49 ± 6.16 cm; 63.44 ± 5.98 kg) who belonged to two different teams of a professional club participated in this study. Data collection was conducted during two seasons (2016-2017, 2017-2018) and included 60 official matches (30 official matches per team). Ten minutes after each match players rated their RPE and using a modified Borg CR-10 scale. A Random Forest Regression was used to quantify the importance of match-related situational variables in RPE. Afterwards, a linear mixed model analysis was applied to identify the variability in RPE among the situational variables. The game-playing time, the player status (starter or substitute) and the player identity were the strongest predictors of RPE. Moreover, the match outcome and the final scoreline showed significant effects on both starter and substitute players but the main effect of the quality of the opponent was only identified in starter players (p < 0.05). These results allow practitioners to know how situational variables interact and modulate RPE after official matches and help them to prescribe and adapt the players' training content and load before and after matches.

Commercially available organolithium compounds as effective, simple precatalysts for silicon-nitrogen heterodehydrocoupling.

A family of commercially available organolithium compounds were found to effectively catalyze the heterodehydrocoupling of silanes and amines under ambient conditions. Ubiquitous nBuLi (1) was utilized as the benchmark catalyst, where an array of primary, secondary, and tertiary arylsilanes were coupled to electron-donating amines, affording aminosilanes in high conversions with short reaction times. Preliminary mechanistic analysis is consistent with a nucleophilic-type system that involves the formation of a hypervalent silicon intermediate. This work underscores the accessibility of Si-N heterodehydrocoupling, with organolithium reagents emerging as some of the most straightforward and cost-effective precatalysts for this transformation.

Chamelogk: A Chromatographic Chameleonicity Quantifier to Design Orally Bioavailable Beyond-Rule-of-5 Drugs.

New chemical modalities in drug discovery include molecules belonging to the bRo5 chemical space. Because of their complex and flexible structure, bRo5 compounds often suffer from a poor solubility/permeability profile. Chameleonicity describes the capacity of a molecule to adapt to the environment through conformational changes; the design of molecular chameleons is a medicinal chemistry strategy simultaneously optimizing solubility and permeability. A default method to quantify chameleonicity in early drug discovery is still missing. Here we introduce Chamelogk, an automated, fast, and cheap chromatographic descriptor of chameleonicity. Moreover, we report measurements for 55 Ro5 and bRo5 compounds and validate our method with literature data. Then, selected case studies (macrocycles, nonmacrocyclic compounds, and PROTACs) are used to illustrate the application of Chamelogk in combination with lipophilicity (BRlogD) and polarity (Δ log kwIAM) descriptors. Overall, we show how Chamelogk deserves being included in property-based drug discovery strategies to design oral bioavailable bRo5 compounds.

Feature Extraction of a Non-Stationary Seismic-Acoustic Signal Using a High-Resolution Dyadic Spectrogram.

Using a novel mathematical tool called the Te-gram, researchers analyzed the energy distribution of frequency components in the scale-frequency plane. Through this analysis, a frequency band of approximately 12 Hz is identified, which can be isolated without distorting its constituent frequencies. This band, along with others, remained inseparable through conventional time-frequency analysis methods. The Te-gram successfully addresses this knowledge gap, providing multi-sensitivity in the frequency domain and effectively attenuating cross-term energy. The Daubechies 45 wavelet function was employed due to its exceptional 150 dB attenuation in the rejection band. The validation process encompassed three stages: pre-, during-, and post-seismic activity. The utilized signal corresponds to the 19 September 2017 earthquake, occurring between the states of Morelos and Puebla, Mexico. The results showcased the impressive ability of the Te-gram to surpass expectations in terms of sensitivity and energy distribution within the frequency domain. The Te-gram outperformed the procedures documented in the existing literature. On the other hand, the results show a frequency band between 0.7 Hz and 1.75 Hz, which is named the planet Earth noise.

Running demands and tactical individual actions of wingers appear to depend on the playing formations within an amateur football team.

We examine the differences in running performance demands and tactical individual actions for male amateur football wingers in four tactical formations: 4-2-3-1, 4-4-2, 3-5-2 and 3-4-2-1 during an entire season. Running demands were assessed in terms of: total distance run; distance traveled at 3 different speed ranges (Jogging, Running, and Sprinting); and number of accelerations registered in two different magnitude bands (Medium and High) while tactical individual actions were assessed through 3269 team match observations. 3-5-2 formation entails the highest running demands, exhibiting significant disparities in Jogging when compared to 4-2-3-1 and 3-5-2, in Sprinting when comparing 4-2-3-1 with both the 3-5-2 and the 3-4-2-1 formations. Moreover, the wingers in the 3-5-2 formation demonstrate the lowest scores in various tactical individual actions, including Shots: 3-5-2 vs. 3-4-2-1; Goal Area Shots: 3-5-2 vs. 3-4-2-1; and Dribbles: 3-5-2 vs. 3-4-2-1. Finally, wingers registered the highest levels of defensive tactical individual actions in 4-4-2 and 3-5-2. Findings suggest it would be of benefit for coaches to focus on formulating specific training plans to address the specific demands placed on wingers playing in these amateur matches and running performance demands and tactical individual actions should be considered together with tactical formation.

Nesting Behavior, Phenology, and Bionomics of the High Andean Leaf-Cutter Bee Megachile (Cressoniella) amparo.

Megachile amparo (González, Revista Colombiana De Entomología 32(1):93-96, 2006) is the only high Andean leaf-cutter bee reported in Colombia and is possibly endemic to the Colombian Andes. Although it is frequently observed, even in urban areas, its biology and ecology remain unknown. The present study aimed to describe detailed aspects of its bionomy. Trap-nests were installed on the Campus of the Nueva Granada University (Cajicá, Colombia) from June/2018 to March/2020. The trap-nests were wooden blocks (25 × 15 × 14 cm) with 30 cavities of Ø = 1 cm and different lengths (50 mm, 75 mm, and 100 mm) lined with waxed paper straws. During the observations, an increasing number of trap-nests were installed, increasing from 250 to 720 cavities. The trap-nests were monitored three times a week, recording both the date the start and end building by female. Most of the nest were maintained in the field to estimate the sex ratio, cell survival, and total development time under natural conditions. Thirty-two nests were removed at different times of the observation period to establish number of cells per nest, and cells built per female per day. We incubated 20 cells from different nests at 18 °C, 22 °C, 26 °C, and 32 °C to estimate the base temperature, thermal constant k (developmental time in degree days), and cell survival. Young cells of different positions were dissected and weighed to characterize food provision and brood cells. Computerized tomography-CT scans were performed in 30 brood cells to determine if diapause occurred during prepupal stage. Females nested 7- and 10-cm-long cavities and the number of cells per nest varied with cavity length. The brood cells had a length of 1.23 ± 0.12 cm and a diameter of 0.92 ± 0.05 cm. The female spends 1.17 ± 0.29 days to build a brood cell. Food provision varied according to the position of the brood cell in the nest. The adults of M. amparo present a marked seasonality being more active during dry months. Base temperature and thermal constant k were different for males and females. The sex ratio is female biased (1.9:1), and cell survival in the field was 89% with no cleptoparasites or predators recorded.

Patients with Chronic Spinal Cord Injury and a Long Period of Evolution Exhibit an Altered Cytokine Production by CD4 and CD8 T Cell Populations.

Spinal cord injury (SCI) is a disabling neurological condition coursing with serious multisystem affections and morbidities. Changes in immune cell compartments have been consistently reported in previous works, representing a critical point of study for understanding the pathophysiology and progression of SCI from acute to chronic stages. Some relevant variations in circulating T cells have been noticed in patients with chronic SCI, although the number, distribution, and function of these populations remain to be fully elucidated. Likewise, the characterization of specific T cell subpopulations and their related cytokine production can aid in understanding the immunopathological role of T cells in SCI progression. In this sense, the objective of the present study was to analyze and quantify the total number of different cytokine-producers T cells in the serum of patients with chronic SCI (n = 105) in comparison to healthy controls (n = 38) by polychromatic flow cytometry. Having this goal, we studied CD4 and CD8 lymphocytes as well as naïve, effector, and effector/central memory subpopulations. SCI patients were classified according to the duration of the lesion in chronic SCI with a short period of evolution (SCI-SP) (comprised between 1 and 5 years since initial injury), early chronic phase (SCI-ECP) (between 5 and 15 years since initial injury) and late-chronic phase (SCI-LCP) (>15 years since initial injury). Our results show that patients with chronic SCI exhibited an altered immune profile of cytokine-producer T cells, including CD4/CD8 naïve, effector, and memory subpopulations in comparison to HC. In particular, IL-10 and IL-9 production seems to be importantly altered, especially in patients with SCI-LCP, whereas changes in IL-17, TNF-α, and IFN-γ T cell populations have also been reported in this and other chronic SCI groups. In conclusion, our study demonstrates an altered profile of cytokine-producer T cells in patients with chronic SCI, with marked changes throughout the course of the disease. In more detail, we have observed significant variations in cytokine production by circulating naive, effector, and effector/central memory CD4 and CD8 T cells. Future studies should be directed to explore the possible clinical consequences of these changes or develop additional translational approaches in these groups of patients.

Abnormal Characterization and Distribution of Circulating Regulatory T Cells in Patients with Chronic Spinal Cord Injury According to the Period of Evolution.

Spinal cord injury (SCI) is a progressive and complex neurological disorder accompanied by multiple systemic challenges. Peripheral immune dysfunction is a major event occurring after SCI, especially in its chronic phase. Previous works have demonstrated significant changes in different circulating immune compartments, including in T cells. However, the precise characterization of these cells remains to be fully unraveled, particularly when considering important variants such as the time since the initial injury. In the present work, we aimed to study the level of circulating regulatory T cells (Tregs) in SCI patients depending on the duration of evolution. For this purpose, we studied and characterized peripheral Tregs from 105 patients with chronic SCI using flow cytometry, with patients classified into three major groups depending on the time since initial injury: short period chronic (SCI-SP, <5 years since initial injury); early chronic (SCI-ECP, from 5-15 years post-injury) and late chronic SCI (SCI-LCP, more than 15 years post-injury. Our results show that both the SCI-ECP and SCI-LCP groups appeared to present increased proportions of CD4+ CD25+/low Foxp3+ Tregs in comparison to healthy subjects, whereas a decreased number of these cells expressing CCR5 was observed in SCI-SP, SCI-ECP, and SCI-LCP patients. Furthermore, an increased number of CD4+ CD25+/high/low Foxp3 with negative expression of CD45RA and CCR7 was observed in SCI-LCP patients when compared to the SCI-ECP group. Taken together, these results deepen our understanding of the immune dysfunction reported in chronic SCI patients and how the time since initial injury may drive this dysregulation.

Macrocycles in Drug Discovery─Learning from the Past for the Future.

We have analyzed FDA-approved macrocyclic drugs, clinical candidates, and the recent literature to understand how macrocycles are used in drug discovery. Current drugs are mainly used in infectious disease and oncology, while oncology is the major indication for the clinical candidates and in the literature Most macrocyclic drugs bind to targets that have difficult to drug binding sites. Natural products have provided 80-90% of the drugs and clinical candidates, whereas macrocycles in ChEMBL have less complex structures. Macrocycles usually reside in the beyond the Rule of 5 chemical space, but 30-40% of the drugs and clinical candidates are orally bioavailable. Simple bi-descriptor models, i.e., HBD ≤ 7 in combination with either MW < 1000 Da or cLogP > 2.5, distinguished orals from parenterals and can be used as filters in design. We propose that recent breakthroughs in conformational analysis and inspiration from natural products will further improve the de novo design of macrocycles.

Transcranial magnetic stimulation-evoked electroencephalography responses as biomarkers for epilepsy: A review of study design and outcomes.

Transcranial magnetic stimulation (TMS) with electroencephalography (EEG), that is TMS-EEG, may assist in managing epilepsy. We systematically reviewed the quality of reporting and findings in TMS-EEG studies on people with epilepsy and healthy controls, and on healthy individuals taking anti-seizure medication. We searched the Cochrane Library, Embase, PubMed and Web of Science databases for original TMS-EEG studies comparing people with epilepsy and healthy controls, and healthy subjects before and after taking anti-seizure medication. Studies should involve quantitative analyses of TMS-evoked EEG responses. We evaluated the reporting of study population characteristics and TMS-EEG protocols (TMS sessions and equipment, TMS trials and EEG protocol), assessed the variation between protocols, and recorded the main TMS-EEG findings. We identified 20 articles reporting 14 unique study populations and TMS methodologies. The median reporting rate for the group of people with epilepsy parameters was 3.5/7 studies and for the TMS parameters was 13/14 studies. TMS protocols varied between studies. Fifteen out of 28 anti-seizure medication trials in total were evaluated with time-domain analyses of single-pulse TMS-EEG data. Anti-seizure medication significantly increased N45, and decreased N100 and P180 component amplitudes but in marginal numbers (N45: 8/15, N100: 7/15, P180: 6/15). Eight articles compared people with epilepsy and controls using different analyses, thus limiting comparability. The reporting quality and methodological uniformity between studies evaluating TMS-EEG as an epilepsy biomarker is poor. The inconsistent findings question the validity of TMS-EEG as an epilepsy biomarker. To demonstrate TMS-EEG clinical applicability, methodology and reporting standards are required.

Functioning of a tripartite lignocellulolytic microbial consortium cultivated under two shaking conditions: a metatranscriptomic study.

BACKGROUND: In a previous study, shaking speed was found to be an important factor affecting the population dynamics and lignocellulose-degrading activities of a synthetic lignocellulolytic microbial consortium composed of the bacteria Sphingobacterium paramultivorum w15, Citrobacter freundii so4, and the fungus Coniochaeta sp. 2T2.1. Here, the gene expression profiles of each strain in this consortium were examined after growth at two shaking speeds (180 and 60 rpm) at three time points (1, 5 and 13 days). RESULTS: The results indicated that, at 60 rpm, C. freundii so4 switched, to a large extent, from aerobic to flexible (aerobic/microaerophilic/anaerobic) metabolism, resulting in continued slow growth till late stage. In addition, Coniochaeta sp. 2T2.1 tended to occur to a larger extent in the hyphal form, with genes encoding adhesion proteins being highly expressed. Much like at 180 rpm, at 60 rpm, S. paramultivorum w15 and Coniochaeta sp. 2T2.1 were key players in hemicellulose degradation processes, as evidenced from the respective CAZy-specific transcripts. Coniochaeta sp. 2T2.1 exhibited expression of genes encoding arabinoxylan-degrading enzymes (i.e., of CAZy groups GH10, GH11, CE1, CE5 and GH43), whereas, at 180 rpm, some of these genes were suppressed at early stages of growth. Moreover, C. freundii so4 stably expressed genes that were predicted to encode proteins with (1) ß-xylosidase/ß-glucosidase and (2) peptidoglycan/chitinase activities, (3) stress response- and detoxification-related proteins. Finally, S. paramultivorum w15 showed involvement in vitamin B2 generation in the early stages across the two shaking speeds, while this role was taken over by C. freundii so4 at late stage at 60 rpm. CONCLUSIONS: We provide evidence that S. paramultivorum w15 is involved in the degradation of mainly hemicellulose and in vitamin B2 production, and C. freundii so4 in the degradation of oligosaccharides or sugar dimers, next to detoxification processes. Coniochaeta sp. 2T2.1 was held to be strongly involved in cellulose and xylan (at early stages), next to lignin modification processes (at later stages). The synergism and alternative functional roles presented in this study enhance the eco-enzymological understanding of the degradation of lignocellulose in this tripartite microbial consortium.

Characterization of patients diagnosed with autoimmune hepatitis in a fourth level hospital from Cali, 2014-2020

Introduction: Autoimmune hepatitis (AIH) is a chronic inflammatory disease of the liver, rarely identified by clinicians to the point of being detected in late stages. It is rare, although there is a lack of epidemiological data. Early diagnosis has implications for the outcomes and development of advanced liver disease. This study describes sociodemographic, clinical, and laboratory characteristics, treatments received and their response and outcomes of interest in adult patients diagnosed with AIH treated at a university hospital in Cali, Colombia. Materials and methods: This observational historical cohort study included patients over 18 years of age of both sexes diagnosed with definitive AIH treated in the emergency services, outpatient clinic, intensive care, and hospitalization at the Fundación Valle del Lili University Hospital between January 2014 and December 2020. Results: 81 patients met the inclusion criteria; 86% were women. The median age was 49 (30-61), and autoimmune disease was comorbidity in 28.4%. Regarding pharmacological treatment, prednisolone and azathioprine were the most frequently used for induction and maintenance. The regimen of prednisolone or prednisolone with azathioprine was used in 79%. Four patients underwent liver transplantation, with no acute liver failure cases. There was only one case of mortality not related to AIH during follow-up. Conclusion: Patients with definitive AIH are mostly middle-aged adults and women, as found in the literature, with a low percentage of cirrhosis and, in earlier stages, low mortality and liver transplantation requirement. The low percentage of liver biopsy is the most critical limitation in the diagnosis and, therefore, in the outcomes of undiagnosed patients.

Introducción: la hepatitis autoinmune (HAI) es una enfermedad inflamatoria crónica del hígado poco identificada por los clínicos, al punto de detectarse en estadios tardíos. Es poco frecuente, aunque hay falta de datos epidemiológicos. El diagnóstico temprano tiene implicaciones en los desenlaces y aparición de enfermedad hepática avanzada. El objetivo de este estudio es describir las características sociodemográficas, clínicas y de laboratorio, así como los tratamientos recibidos y la respuesta a estos, y los desenlaces de interés de los pacientes adultos con diagnóstico de hepatitis autoinmune atendidos en un hospital universitario de la ciudad de Cali, Colombia. Materiales y métodos: estudio observacional de cohorte histórica que incluyó a pacientes mayores de 18 años de ambos sexos con diagnóstico de HAI con puntaje definitivo atendidos en los servicios de urgencias, consulta externa, cuidado intensivo y hospitalización en el Hospital Universitario Fundación Valle del Lili entre enero de 2014 y diciembre de 2020. Resultados: un total de 81 pacientes cumplió los criterios de inclusión. El 86% de los pacientes eran mujeres, la mediana de edad fue de 49 años (de 30 a 61) y hubo presencia de enfermedad autoinmune como comorbilidad en el 28,4%. Sobre el tratamiento farmacológico, prednisolona y azatioprina fueron los medicamentos más frecuentemente utilizados para el tratamiento de inducción y mantenimiento. El esquema de prednisolona o prednisolona con azatioprina se aplicó en el 79%. Cuatro pacientes fueron llevados a trasplante hepático y no se presentaron casos de insuficiencia hepática aguda. Se presentó un solo caso de mortalidad no relacionada con la HAI durante el tiempo de seguimiento. Conclusión: los pacientes con HAI definitivo son en su mayoría adultos de mediana edad y mujeres, similar a lo encontrado en la literatura, con un bajo porcentaje de cirrosis y en estadios más tempranos, baja mortalidad y requerimiento de trasplante hepático. El bajo porcentaje de biopsia hepática es la limitante más importante en el diagnóstico y, por ende, en los desenlaces de los pacientes no diagnosticados.