Bintrafusp alfa and chemotherapy as first-line treatment in biliary tract cancer: A randomized phase 2/3 trial.

BACKGROUND AND AIMS: We compared the safety and efficacy of bintrafusp alfa (BA) in combination with gemcitabine+cisplatin (GemCis), to those of GemCis alone, in patients with biliary tract cancer (BTC). APPROACH AND RESULTS: This randomized, double-blind, placebo-controlled, adaptive design phase 2/3 trial (NCT04066491) included treatment-naïve adults with locally advanced/metastatic BTC. Patients (N=297) were randomized to receive an intravenous infusion of BA (2400 mg once/3 wk) plus GemCis (gemcitabine 1000 mg/m2+cisplatin 25 mg/m2 on days 1 and 8/3 wk; 8 cycles) (BA group, n=148) or placebo+GemCis (placebo group, n=149). The primary endpoint was overall survival (OS). For adaptation analysis (phase 2-phase 3; data cut-off: May 20, 2021), efficacy was assessed in the first 150 patients who were antibiotic-naïve, when 80 progression-free survival events had occurred and ≥19 weeks of follow-up had been completed (BA, n=73; placebo, n=77). Median OS (95% CI) for the BA (11.5 mo [9.3-not estimable, NE]) and placebo (11.5 mo [10.0-NE]) groups was comparable (hazard ratio 1.23 [95% CI 0.66-2.28]; p=0.7394); OS data maturity was 27.2% (41 events/151 patients). The most common grade ≥3 treatment-related adverse event was anemia (BA, 26.0%; placebo, 22.8%). Bleeding adverse events were reported more frequently in the BA group (28.8%) versus the placebo group (7.4%). Deaths within 60 days of the first dose were reported in 7.5% and 1.3% of patients in the BA and placebo groups, respectively. CONCLUSIONS: BA+GemCis did not provide a clinically meaningful benefit compared to GemCis alone as first-line treatment for BTC and the study was discontinued early (terminated: August 20, 2021).

Predictors of response to immunotherapy in colorectal cancer.

Colorectal cancer (CRC) is a major cause of cancer-related deaths globally. While treatment advancements have improved survival rates, primarily through targeted therapies based on KRAS, NRAS, and BRAF mutations, personalized treatment strategies for CRC remain limited. Immunotherapy, mainly immune checkpoint blockade, has shown efficacy in various cancers but is effective in only a small subset of patients with CRC with deficient mismatch repair (dMMR) proteins or high microsatellite instability (MSI). Recent research has challenged the notion that CRC is immunologically inert, revealing subsets with high immunogenicity and diverse lymphocytic infiltration. Identifying precise biomarkers beyond dMMR and MSI is crucial to expanding immunotherapy benefits. Hence, exploration has extended to various biomarker sources, such as the tumor microenvironment, genomic markers, and gut microbiota. Recent studies have introduced a novel classification system, consensus molecular subtypes, that aids in identifying patients with CRC with an immunogenic profile. These findings underscore the necessity of moving beyond single biomarkers and toward a comprehensive understanding of the immunological landscape in CRC, facilitating the development of more effective, personalized therapies.

CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor-Mutated Advanced Non-Small-Cell Lung Cancer.

PURPOSE: We report CNS efficacy of first-line osimertinib plus chemotherapy versus osimertinib monotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) from the phase III FLAURA2 study according to baseline CNS metastasis status. METHODS: Patients were randomly assigned to osimertinib plus platinum-pemetrexed (combination) or osimertinib monotherapy until disease progression or discontinuation. Brain scans were performed in all patients at baseline and progression and at scheduled assessments until progression for patients with baseline CNS metastases; scans were assessed by neuroradiologist CNS blinded independent central review (BICR). RESULTS: On the basis of baseline CNS BICR, 118 of 279 (combination) and 104 of 278 (monotherapy) randomly assigned patients had ≥one measurable and/or nonmeasurable CNS lesion and were included in the CNS full analysis set (cFAS); 40 of 118 and 38 of 104 had ≥one measurable target CNS lesion and were included in the post hoc CNS evaluable-for-response set (cEFR). In the cFAS, the hazard ratio (HR) for CNS progression or death was 0.58 (95% CI, 0.33 to 1.01). In patients without baseline CNS metastases, the HR for CNS progression or death was 0.67 (95% CI, 0.43 to 1.04). In the cFAS, CNS objective response rates (ORRs; 95% CI) were 73% (combination; 64 to 81) versus 69% (monotherapy; 59 to 78); 59% versus 43% had CNS complete response (CR). In the cEFR, CNS ORRs (95% CI) were 88% (73 to 96) versus 87% (72 to 96); 48% versus 16% had CNS CR. CONCLUSION: Osimertinib plus platinum-pemetrexed demonstrated improved CNS efficacy compared with osimertinib monotherapy, including delaying CNS progression, irrespective of baseline CNS metastasis status. These data support this combination as a new first-line treatment for patients with EGFR-mutated advanced NSCLC, including those with CNS metastases.

Thoracic Complications of Liver-Directed Therapy and Interventions.

ABSTRACT: Liver-directed percutaneous and endovascular therapies are effective methods to diagnose and treat various hepatic disorders and malignancies. Because of the close anatomic proximity of the liver to the right hemidiaphragm, pleura, and lung bases, complications can arise involving these structures. Although they are rare, awareness of intrathoracic complications associated with liver-directed therapies and their imaging features will ensure timely detection and management. We aim to review the clinical and imaging features of thoracic complications related to liver-directed therapy and interventions.

The willingness to forgive among the Wayuu and among people from other indigenous communities in Colombia

Introduction/Objectives: Willingness to forgive has been studied in different situations, however, there are no published studies in Colombia with indigenous populations and taking into account their worldview. The present research was aimed at examining the willingness to forgive of people from various ethnic minorities in Colombia such as the Embera, Nasa, Pijao and Kaamash-Hu communities and focusing in particular on the Wayuu community. Method: An experimental design was used and a cluster analysis was performed. The sample was composed of 159 indigenous adults (30% male) between the ages of 18 and 76, who were shown a series of scenarios describing a common situation in which an orchard was damaged by domestic animals belonging to a neighbour. Three factors were manipulated in the scenario: the severity of the damage, the level of carelessness of the animals' owner, and the animals' owner's explanations and apologetic behaviour. Results: Cluster analysis yielded five qualitatively different positions: Never forgive under any circumstances (6% of the sample, primarily participants from the Embera community), Depends on apology and neglect (15%), Depends on apology, consequences, and neglect (30%, primarily participants from the Kaamash-Hu community), and Almost always forgive (36%, primarily people from the Wayuu community). Conclusion: Thus, there is a convergence between the results of this study and the anthropological observations of the participating ethnic communities. Forgiveness is closely linked to the cosmovision of each indigenous group.

Introducción/Objetivos: La voluntad de perdonar ha sido estudiada en diferentes situaciones, sin embargo, no existen estudios publicados en Colombia con población indígena y teniendo en cuenta su cosmovisión. La presente investigación tuvo como objetivo examinar la voluntad a perdonar de personas de diversas minorías étnicas en Colombia como la comunidad Embera, Nasa, Pijao, Kaamash-Hu y centrándose en particular en la comunidad Wayuu. Método: Se presentaron una serie de escenarios a una muestra de 159 adultos indígenas (30% hombres) de entre 18 y 76 años. Dichos escenarios describían una situación común en la que una huerta era dañada por animales domésticos de un vecino. Se manipularon tres factores en cada escenario: la gravedad del daño, el nivel de descuido del dueño de los animales y, las explicaciones y el comportamiento de disculpa del dueño de los animales. Resultados: El análisis de clústeres arrojó cinco posiciones cualitativamente diferentes: Nunca perdona bajo ninguna circunstancia (6% de la muestra, principalmente participantes de la comunidad Embera), Depende de las disculpas y del descuido (15%), Depende de las disculpas, las consecuencias y el descuido (30%, principalmente participantes de la comunidad Kaamash-Hu), y Casi siempre perdona (36%, principalmente personas de la comunidad Wayuu). Conclusiones: Por tanto, existe una convergencia entre los resultados de este estudio y las observaciones antropológicas que condujeron a la decisión de la Unesco de considerar el sistema de justicia restaurativa de la comunidad Wayuu como un patrimonio inalterable.

Intervención digital basada en la atención plena para estrés y ansiedad generalizada en trabajadores universitarios / Digital intervention based on mindfulness for stress and generalized anxiety in university workers

Resumen Objetivo: Analizar el efecto y la percepción de una intervención digital, basada en atención plena para disminuir el estrés y ansiedad generalizada entre los trabajadores de la Universidad Veracruzana (UV). Materiales y Métodos: Un ensayo clínico aleatorizado se llevó a cabo con 102 participantes, divididos en un grupo experimental y un grupo control para evaluar el efecto de una intervención a través de WhatsApp, en la reducción del estrés y la ansiedad. El grupo experimental recibió un programa de meditación con el fin de capacitarlos y enseñarles a practicar la atención plena. Se utilizaron las escalas de estrés percibido PSS-10 y del trastorno de la ansiedad generalizada GAD-7 para evaluar el efecto de la intervención. Los participantes expresaron su opinión sobre la intervención mediante entrevistas focalizadas con preguntas estandarizadas. Resultados: Se encuentra una disminución en las medianas del nivel de estrés percibido y ansiedad generalizada del grupo experimental entre el momento pre-intervención y post-intervención, con una diferencia estadísticamente significativa, p=0.012 y p=0.013, respectivamente. En el grupo control se visualiza un ligero aumento en dichos niveles y no se identifican diferencias significativas entre la medición basal y final, tanto en estrés como en ansiedad. En el análisis del espectro del discurso, se examinó la categoría de "Usabilidad" y se identificaron diferentes aspectos relacionados con la percepción, participación y recomendación de la intervención. Conclusiones: Se encontró una mejoría estadísticamente significativa en los niveles de estrés y ansiedad generalizada. Se demuestra que, realizar intervenciones en salud pública que involucren la tecnología, es cada vez más adaptable y contribuye al avance del conocimiento dentro del autocuidado de la salud mental entre los trabajadores de la Universidad Veracruzana.

Abstract Objective: To analyze the effect and perception of a digital intervention, based on mindfulness to reduce stress and generalized anxiety among workers at the Universidad Veracruzana (UV). Materials and Methods: A randomized clinical trial was carried out with 102 participants, divided into an experimental group and a control group to evaluate the effect of an intervention through WhatsApp in reducing stress and anxiety. The experimental group received a meditation program in order to train and teach them to practice mindfulness. The PSS-10 Perceived Stress and GAD-7 Generalized Anxiety Disorder scales were used to assess the effect of the intervention. Participants expressed their opinion about the intervention through focused interviews with standardized questions. Results: There is a decrease in the median level of perceived stress and generalized anxiety of the experimental group between the pre-intervention and post-intervention moments, with a statistically significant difference, p=0.012 and p=0.013, respectively. In the control group, a slight increase in said levels was observed and no significant differences were identified between the baseline and final measurement, both in stress and anxiety. In the discourse spectrum analysis, the "Usability" category was examined and different aspects related to the perception, participation and recommendation of the intervention were identified. Conclusions: A statistically significant improvement was found in the levels of stress and generalized anxiety. It is shown that carrying out public health interventions that involve technology is increasingly adaptable and contributes to the advancement of knowledge within mental health self-care among workers at the Universidad Veracruzana.

Clinical and Endoscopic Characterization of Gastrointestinal Kaposi's Sarcoma in an Institution in Southwestern Colombia between 2011 and 2020

Kaposi's sarcoma is an angioproliferative neoplasm associated with the human herpesvirus 8. According to the clinical characteristics and the degree of immunosuppression, there are four epidemiological forms: classic, endemic, iatrogenic, and epidemic. The latter is associated with acquired immunodeficiency syndrome (AIDS) and 40% GI involvement. There is little epidemiological, clinical, and endoscopic evidence of the disease. This study sought to characterize this condition in a Colombian population and compare the findings with publications from other countries. One hundred thirty-five records of patients who consulted between 2011 and 2020 for Kaposi's sarcoma were reviewed, of which 24 had GI involvement. Epidemiological, clinical, endoscopic, and treatment characteristics were obtained. Twenty-two patients were men. There were 21 patients infected with human immunodeficiency virus (HIV; 87.5%) and 19 receiving antiretroviral therapy (90%); 33.3% had HIV viral load > 100,000 copies/mL. The CD4+ count was <50 cells/µL in 28.6% of cases, between 50 and 100 cells/µL in 19.0%, and between 100 and 200 cells/µL in 14.4%. The rate of infection by other opportunistic infections was 41.7%. There were GI symptoms in 33% of the patients, and the most frequent were hematochezia, abdominal pain, nausea, and diarrhea. Most had concomitant skin lesions (70.8%). GI lesions were located mainly in the oropharynx (41.7%), stomach (20.8%), and colon (16.7%). The most common endoscopic finding was maculopapular erythema. This article provided insight into the local epidemiology of gastrointestinal Kaposi's sarcoma. In contrast to studies in other populations, GI symptoms were more frequent in this one, and there was a difference in endoscopic findings. Studies with larger populations are needed.

El sarcoma de Kaposi es una neoplasia angioproliferativa asociada al virus del herpes humano 8. Según las características clínicas y el grado de inmunosupresión, son cuatro las formas epidemiológicas: clásica, endémica, iatrogénica y epidémica, esta última asociada al síndrome de inmunodeficiencia adquirida (SIDA) y con un 40% de compromiso gastrointestinal. Existe escasa evidencia epidemiológica, clínica y endoscópica de la enfermedad. Este estudio buscó caracterizar esta condición en una población colombiana y contrastar los hallazgos con publicaciones de otros países. Se revisaron 135 registros de pacientes que consultaron entre el 2011 y 2020 por sarcoma de Kaposi, de los cuales 24 tenían compromiso gastrointestinal. Se obtuvieron características epidemiológicas, clínicas, endoscópicas y tratamientos. Veintidós pacientes eran hombres. Hubo 21 pacientes infectados por virus de la inmunodeficiencia humana (VIH; 87,5%) y 19 recibían terapia antirretroviral (90%). El 33,3% tenía carga viral VIH > 100 000 copias/mL. El recuento de CD4+ fue < 50 cel/µL en el 28,6% de los casos, entre 50 y 100 cel/µL en el 19,0%, y entre 100 y 200 cel/µL en el 14,4%. La tasa de infecciones por otros oportunistas fue de 41,7%. Hubo síntomas gastrointestinales en el 33% de los pacientes y los más frecuentes fueron hematoquecia, dolor abdominal, náuseas y diarrea. La mayoría tuvo lesiones cutáneas concomitantes (70,8%). Las lesiones gastrointestinales se localizaron principalmente en la orofaringe (41,7%), estómago (20,8%) y colon (16,7%). El hallazgo endoscópico más común fue eritema maculopapular. Este artículo mostró una visión de la epidemiología local del sarcoma de Kaposi gastrointestinal. En contraste con estudios en otras poblaciones, en este, los síntomas gastrointestinales fueron más frecuentes y hubo diferencia en los hallazgos endoscópicos. Son necesarios estudios con poblaciones más grandes.

Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results.

PURPOSE: Despite marked advances in the treatment of unresectable or metastatic melanoma, the need for novel therapies remains. Bempegaldesleukin (BEMPEG), a pegylated interleukin-2 (IL-2) cytokine prodrug, demonstrated efficacy in the phase II PIVOT-02 trial. PIVOT IO 001 (ClinicalTrials.gov identifier: NCT03635983) is a phase III, randomized, open-label study that builds on the PIVOT-02 results in first-line melanoma. METHODS: Patients with previously untreated, unresectable, or metastatic melanoma were randomly assigned 1:1 to receive BEMPEG plus nivolumab (NIVO) or NIVO monotherapy. Primary end points were objective response rate (ORR) and progression-free survival (PFS) by blinded independent central review and overall survival (OS). Secondary and exploratory end points included additional efficacy measures, safety, and pharmacokinetics (PKs) and pharmacodynamics analyses. RESULTS: In 783 patients (n = 391, BEMPEG plus NIVO; n = 392, NIVO monotherapy), the median follow-up was 11.6 months in the intent-to-treat population. The ORR with BEMPEG plus NIVO was 27.7% versus 36.0% with NIVO (two-sided P = .0311). The median PFS with BEMPEG plus NIVO was 4.17 months (95% CI, 3.52 to 5.55) versus 4.99 months (95% CI, 4.14 to 7.82) with NIVO (hazard ratio [HR], 1.09; 97% CI, 0.88 to 1.35; P = .3988). The median OS was 29.67 months (95% CI, 22.14 to not reached [NR]) with BEMPEG plus NIVO versus 28.88 months (95% CI, 21.32 to NR) with NIVO (HR, 0.94; 99.929% CI, 0.59 to 1.48; P = .6361). Grade 3-4 treatment-related adverse events (AEs) and serious AE rates were higher with the combination (21.7% and 10.1%, respectively) versus NIVO (11.5% and 5.5%, respectively). BEMPEG PK exposure and absolute lymphocyte count changes after BEMPEG plus NIVO were comparable between PIVOT IO 001 and PIVOT-02. CONCLUSION: The PIVOT IO 001 study did not meet its primary end points of ORR, PFS, and OS. Increased toxicity was observed with BEMPEG plus NIVO versus NIVO.

Neutralización del virus SARS-CoV-2 (linaje B.1.1) por suero hiperinmune de llama (Lama glama) en cultivo de células Vero / Neutralization of SARS-CoV-2 (lineage B.1.1) by hyperimmune llama (Lama glama) serum in Vero cell culture

Objetivo. Evaluar la respuesta serológica de anticuerpos de una llama (Lama glama) a la inmunización del virus SARS-CoV-2 (linaje B.1.1) y la capacidad neutralizante del suero de llama hiperinmune frente al virus SARS-CoV-2 (linaje B.1.1) en células Vero. Materiales y métodos. Se inmunizó una llama con el virus SARS-CoV-2 inactivado (Linaje B.1.1) y se analizaron muestras de suero para evaluar el nivel de anticuerpos mediante ELISA, así como la reactividad a antígenos de SARS-CoV-2 mediante Western Blot. Además, se evaluó la neutralización viral en cultivos celulares por la Prueba de Neutralización por Reducción de Placas (PRNT, por sus siglas en inglés). Resultados. Se observó un aumento en la serorreactividad en la llama inmunizada desde la semana 4 en adelante. Los títulos de anticuerpos fueron más elevados en el séptimo refuerzo de inmunización. Los resultados de Western Blot confirmaron los hallazgos positivos del ELISA, y los anticuerpos del suero inmune reconocieron varias proteínas virales. El ensayo de neutralización (PRNT) mostró una neutralización viral visible, concordante con los resultados de ELISA y Western Blot. Conclusiones. Los hallazgos sugieren que el suero hiperinmune de llama podría constituir una fuente de anticuerpos terapéuticos contra las infecciones por el virus SARS-CoV-2 (linaje B.1.1) y que deberá ser evaluado en estudios posteriores.

Objective. To evaluate the serological antibody response of a llama (Lama glama) to SARS-CoV-2 (B.1.1 lineage) immunization and the neutralizing capacity of hyperimmune llama serum against SARS-CoV-2 virus (B.1.1 lineage) in Vero cells. Materials and methods. A llama was immunized with inactivated SARS-CoV-2 (B.1.1 lineage). Serum samples were analyzed to evaluate the level of antibodies by ELISA, as well as reactivity to SARS-CoV-2 antigens by Western Blot. In addition, viral neutralization in cell cultures was assessed by the Plate Reduction Neutralization Test (PRNT). Results . Seroreactivity increased in the immunized llama from week 4 onwards. Antibody titers were the highest after the seventh immunization booster. Western blot results confirmed the positive ELISA findings, and immune serum antibodies recognized several viral proteins. The neutralization assay (PRNT) showed visible viral neutralization, which was in accordance with the ELISA and Western Blot results. Conclusions. The findings suggest that hyperimmune llama serum could constitute a source of therapeutic antibodies against SARS-CoV-2 infections (lineage B.1.1), and should be studied in further research.

MAP4K4 and cancer: ready for the main stage?

MAP4K4 is a serine/threonine kinase that belongs to the MAP kinase family and plays a critical role in embryogenesis and cellular migration. It contains approximately 1,200 amino acids and has a molecular mass of 140 kDa. MAP4K4 is expressed in most tissues where it has been examined and its knockout is embryonic lethal due to impaired somite development. Alterations in MAP4K4 function have a central role in the development of many metabolic diseases such as atherosclerosis and type 2 diabetes, but have recently been implicated in the initiation and progression of cancer. For example, it has been shown that MAP4K4 can stimulate the proliferation and invasion of tumor cells by activating pro-proliferative pathways (such as the c-Jun N-terminal kinase [JNK] and mixed-lineage protein kinase 3 [MLK3] pathways), attenuate anti-tumor cytotoxic immune responses, and stimulate cell invasion and migration by altering cytoskeleton and actin function. Recent in vitro experiments using RNA interference-based knockdown (miR) techniques have shown that inhibition of MAP4K4 function reduces tumor proliferation, migration, and invasion, and may represent a promising therapeutic approach in many types of cancer such as pancreatic cancer, glioblastoma, and medulloblastoma, among others. Over the last few years, specific MAP4K4 inhibitors such as GNE-495 have been developed but have not yet been tested in cancer patients. However, these novel agents may be useful for cancer treatment in the future.

Use of Virtual Reality and Three-Dimensional Printing in the Surgical Planning of Slide Tracheoplasty.

Purpose: To describe our experience using virtual reality (VR) and three-dimensional (3D) printing as complements for the surgical planning process of slide tracheoplasty (ST) in patients with congenital tracheal stenosis (CTS). Description: VR and 3D printing are used for the surgical planning of ST as a therapeutic option in three female patients under five years of age with CTS. Evaluation: We assessed the planned surgical procedure, procedural time, postoperative complications, and outcomes, as well as the main surgeon's experience with the use of the applied technologies. Conclusions: The interaction within the VR environment allowed for collaboration of the surgical plan between surgical staff and enhancement of the radiologist-surgeon communication, while procedural simulation with 3D printing prototypes allowed for refining technical abilities for the surgical interventions. Based on our experience, the application of these technologies have added value to the surgical planning of ST and its outcomes in the treatment of CTS.

Imaging modalities (MRI, CT, PET/CT), indications, differential diagnosis and imaging characteristics of cystic mediastinal masses: a review.

Cystic mediastinal masses have traditionally represented a diagnostic dilemma with differentiation of malignant masses a particular area of concern. Each imaging modality has strengths and weaknesses in mediastinal imaging-computed tomography (CT) offers increased spatial resolution at the cost of poorer soft tissue differentiation and requiring ionizing radiation, while magnetic resonance imaging (MRI) offers superior soft tissue contrast/characterization at significantly greater cost. Ultrasound offers real-time visualization but is operator and tissue dependent. [18F]fluoro-D-glucose (F-18 FDG) positron emission tomography (F-18 FDG PET) CT provides functional information, but poorer spatial resolution. Recent advances have focused upon the use of magnetic resonance imaging to aid in characterization of cystic mediastinal lesions, particularly in the context of indeterminate CT findings. The mediastinum may be divided into three anatomic compartments: prevascular, visceral, and paravertebral. All three compartments extend superiorly from the thoracic inlet and inferiorly to the diaphragm. These compartments provide a useful framework for categorizing normal and pathologic mediastinal processes. In this article, we will review the imaging characteristics of mediastinal cystic lesions via a case-based review divided by anatomical mediastinal compartments. Characteristic imaging features and troubleshooting are particular areas of focus. Normal variants that may mimic cystic pathology are discussed. The roles of CT and MRI will be emphasized. Cases from our institution are presented as illustrative examples.

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.

Factors associated with frequent marijuana consumption in young people before admission to juvenile detention centers in Peru. / Factores asociados al consumo frecuente de marihuana en jóvenes antes de su ingreso a centros juveniles de diagnóstico y rehabilitación en Perú.

Marijuana is the most widely used illicit drug in the world, especially among young people. This study is relevant to policy makers because it expands the knowledge regarding drug use in vulnerable youth, allowing health authorities to reduce marijuana consumption via educational, family, and governmental strategies and policies. The objective of this study was to determine the prevalence of frequent marijuana consumption and its associated factors in young people before admission to juvenile detention centers in Peru. The data was taken from the 2016 National Population Census of the Youth Diagnostic and Rehabilitation Centers in Peru. The final sample was made up of 1,848 people with ages between 14 and 22 years old, with a median age of 17 (95.6% males). The variable frequent marijuana consumption was defined as the use of marijuana at least once a week, prior to entering the center. The main factors associated with frequent marijuana use were male sex, running away from home before the age of 15, physical abuse during childhood, having a family member who consumed alcohol or drugs frequently, and the presence of criminal gangs in the housing area. Additionally, it was found that living with parents up to a specific critical age decreases the probability of frequent use of marijuana in young people. These results could aid the development of strategies and public policies that help prevent the consumption of marijuana and other drugs from an early age.

La marihuana es la droga ilícita más consumida en el mundo, especialmente entre jóvenes. El presente estudio es relevante para la toma de decisiones en salud porque expande el conocimiento sobre el uso de drogas en la juventud vulnerable y permite a las autoridades sanitarias reducir el consumo de marihuana mediante estrategias educativas, familiares y gubernamentales. El objetivo de este estudio fue determinar la prevalencia del consumo frecuente de marihuana y sus factores asociados en jóvenes antes de su ingreso a centros juveniles de diagnóstico y rehabilitación en Perú. Los datos fueron tomados del Censo Nacional de Población en los Centros Juveniles de Diagnóstico y Rehabilitación del año 2016 en Perú. La muestra final estuvo compuesta por 1848 personas entre 14 y 22 años, con una mediana de edad de 17 años (95,6 % hombres). La variable consumo frecuente de marihuana fue definida como el consumo de marihuana de al menos una vez por semana por parte de los jóvenes, previo a su ingreso al centro. Los principales factores asociados al consumo frecuente de marihuana fueron el sexo masculino, huir de casa antes de los 15 años, haber sufrido abuso físico durante la infancia, tener un miembro de la familia que consuma alcohol o drogas frecuentemente y la presencia de pandillas criminales en la zona residencial. Asimismo, se halló que vivir con los padres hasta cierta edad crítica disminuye la probabilidad de consumo frecuente de marihuana en jóvenes. Estos resultados podrían ayudar a desarrollar estrategias y políticas públicas que ayuden a prevenir el consumo de marihuana y otras drogas desde edades tempranas.

Tofacitinib in the treatment of moderate to severe ulcerative colitis in Colombia: Real world experience. / Tofacitinib en el tratamiento de la colitis ulcerosa moderada a grave en Colombia: experiencia en mundo real.

INTRODUCTION: There are no studies on efficacy of tofacitinib for ulcerative colitis (UC) in Latin America. The aim of this study was to describe the efficacy and safety, in the real world, of patients with moderate-severe UC treated with tofacitinib in our setting. MATERIALS AND METHODS: Multicenter descriptive observational study, in patients with UC who received treatment with tofacitinib in induction phase for 8 weeks and then, maintenance therapy, between June 2019 and June 2022. RESULTS: Thirty-four adult patients, 50% female, mean age 38.1 (range 22-72) years. 76.5% pancolitis, and 20.6% left colitis. 79.4% failure to tumor necrosis factor inhibitors (anti-TNFs), and 35.3% to vedolizumab. 14.7% naïve to biologic therapy. 23.5% had previous extraintestinal manifestations. During induction, 58.8% of patients achieved clinical, biochemical and endoscopic remission. During maintenance, 76.9% of patients at 26 weeks and 66.6% at 52 weeks presented clinical remission. Eight patients presented adverse events, none of them cardiovascular or thromboembolic. 44.1% were steroid-dependent, and 23.5% required steroids as rescue therapy. 38.3% required an increase in tofacitinib to 10mg every 12h during maintenance. In 17.6% tofacitinib was discontinued due to lack of efficacy. We included three pediatric-aged female patients, mean age 15.3 (range 14-17) years, 2/3 with pancolitis and 1/3 with left colitis, all with prior exposure to biologic therapy, who had clinical, biologic and endoscopic remission at induction. CONCLUSIONS: In this first Latin American study with tofacitinib in UC, efficacy and safety are demonstrated in the treatment of our patients with moderate to severe activity.

Consensus Virtual Screening Protocol Towards the Identification of Small Molecules Interacting with the Colchicine Binding Site of the Tubulin-microtubule System.

Modification of the tubulin-microtubule (Tub-Mts) system has generated effective strategies for developing different treatments for cancer. A huge amount of clinical data about inhibitors of the tubulin-microtubule system have supported and validated the studies on this pharmacological target. However, many tubulin-microtubule inhibitors have been developed from representative and common scaffolds that cover a small region of the chemical space with limited structural innovation. The main goal of this study is to develop the first consensus virtual screening protocol for natural products (ligand- and structure-based drug design methods) tuned for the identification of new potential inhibitors of the Tub-Mts system. A combined strategy that involves molecular similarity, molecular docking, pharmacophore modeling, and in silico ADMET prediction has been employed to prioritize the selections of potential inhibitors of the Tub-Mts system. Five compounds were selected and further studied using molecular dynamics and binding energy predictions to characterize their possible binding mechanisms. Their structures correspond to 5-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2,3-dimethoxyphenol (1), 9,10-dihydro-3,4-dimethoxy-2,7-phenanthrenediol (2), 2-(3,4-dimethoxyphenyl)-5,7-dihydroxy-6-methoxy-4H-1-benzopyran-4-one (3), 13,14-epoxyparvifoline-4',5',6'-trimethoxybenzoate (4), and phenylmethyl 6-hydroxy-2,3-dimethoxybenzoate (5). Compounds 1-3 have been associated with literature reports that confirm their activity against several cancer cell lines, thus supporting the utility of this protocol.

Clonación del gen caf1 de yersinia pestis en el centro nacional de productos biológicos del Instituto Nacional de Salud / Cloning of the caf1 gene from yersinia pestis at the National Center for Biological Products of the National Institute of Health

El objetivo del presente trabajo fue amplificar y clonar la secuencia codificante del gen caf1 de Yersinia pestis en el plásmido pET32a (+). Para esta investigación, se empleó una cepa nativa Y.

El regreso a clases presenciales de educación física ante la COVID-19 en México / The return to face-to-face physical education classes against COVID-19 in Mexico / O retorno às aulas presenciais de educação física antes do COVID-19 no México

La presente investigación tuvo como objetivo conocer el nivel de cumplimiento de las medidas académicas y de salud, limpieza e higiene que se implementaron en la sesión de educación física en el regreso a clases presenciales en México. Para ello, se siguió un diseño cuantitativo no experimental de corte transversal, a través de la cual se recogió información por medio de una escala tipo Likert. Los resultados indican que el 55% de los profesores de educación física están de acuerdo en que las medidas académicas establecidas, les facilitó lograr la recuperación y reforzamiento de los aprendizajes de sus alumnos, así mismo, el 81,2% afirma que se están llevando a cabo medidas preventivas de contagio y mitigación de la COVID-19 en las actividades escolares. Se concluye que las medidas propuestas por las autoridades educativas para el regreso a clases presenciales son aceptables, sin embargo, se identifican limitantes en lo que se refiere al abasto de materiales de sanitización y limpieza entregados por las autoridades educativas.

This research was conducted in order to determine the level of compliance to the health, cleanliness, and hygiene measures implemented during physical education sessions when returning to school in Mexico. For this purpose, a non-experimental cross-sectional quantitative design was followed, through which information was collected by means of a Likert-type scale. The results indicate that 55% of the physical education teachers agree that the measures established helped them to recover and reinforce what their students learnt. Likewise, 81,2% assert that they are now carrying out preventive measures for the contagion and mitigation of COVID-19 during school activities. It is concluded that the measures proposed by the educational authorities for the return to school are acceptable. However, there are some limitations identified in terms of the supply of sanitizing and cleaning materials provided by the educational authorities.

O objetivo desta pesquisa foi determinar o nível de cumprimento das medidas acadêmicas e de saúde, limpeza e higiene que foram implementadas na sessão de educação física ao retornar às aulas presenciais no México. Para isso, seguiu-se um delineamento quantitativo transversal não experimental, por meio do qual as informações foram coletadas por meio de uma escala do tipo Likert. Os resultados indicam que 55% dos professores de educação física concordam que as medidas acadêmicas estabelecidas facilitam a recuperação e o reforço da aprendizagem de seus alunos, da mesma forma, 81,2% afirmam que estão realizando medidas preventivas de contágio e mitigação de COVID-19 nas atividades escolares. Conclui-se que as medidas propostas pelas autoridades educacionais para o retorno às aulas presenciais são aceitáveis, porém, são identificadas limitações quanto ao fornecimento de materiais de higienização e limpeza entregues pelas autoridades educacionais.