Outcomes of re-referrals of patients with alcohol-associated liver disease, who were previously declined for liver transplantation.

Since 2018, our program has utilized specific psychosocial criteria and a multidisciplinary approach to assess patients for liver transplant due to alcohol-associated liver disease (ALD), rather than the 6-month abstinence rule alone. If declined based on these criteria, specific recommendations are provided to patients and their providers regarding goals for re-referral to increase the potential for future transplant candidacy. Recommendations include engagement in treatment for alcohol use disorder, serial negative biomarker testing, and maintenance of abstinence from alcohol. In our current study, we evaluate the outcomes of patients with ALD, who were initially declined upon assessment and re-referred to our program. This is a retrospective cohort study that includes 98 patients with ALD, who were previously declined for liver transplantation and were subsequently re-referred for liver transplant assessment between May 1, 2018, and December 31, 2021. We assess the outcomes of patients who were re-referred including acceptance for transplantation following a second assessment. Of the 98 patients who were re-referred, 46 (46.9%) fulfilled the recommendations made and proceeded to further medical evaluation. Nine were eventually transplanted; others are listed and are waiting for transplant. The presence of a partner was independently associated with a higher rate of acceptance (OR 0.16, 95% CI: 0.03-0.97, p = 0.05). Most of the patients who did not proceed further (n = 52) were declined again due to ALD contraindications (n = 33, 63.4%), including ongoing drinking and lack of engagement in recommended addiction treatment. Others had medical contraindications (11.2%), clinically improved (6.1%), had adherence issues (5.1%), or lack of adequate support (2%). Patients with ALD previously declined for a liver transplant can be re-referred and successfully accepted for transplantation by fulfilling the recommendations made by the multidisciplinary team. Important factors including ongoing abstinence, engagement in addiction treatment, and social support are key for successful acceptance.

Factors associated with coronary artery disease among people living with human immunodeficiency virus: Results from the Colombian HIV/AIDS registry.

Background: People living with HIV (PLWHIV) are at a higher risk of developing coronary artery disease (CAD). We aimed to assess the factors associated with CAD among PLWHIV in Colombia. Methods: We conducted a retrospective cohort study based on adults newly diagnosed with HIV, reported to the Colombian HIV/AIDS registry from 2018 to 2021. Baseline demographic and clinical characteristics were compared by age (<50 and ≥ 50 years). Our main outcome was the presence of CAD. Logistic regression models were used to assess the association between traditional and HIV-related factors with CAD. These associations were also evaluated in stratified models by age. Effect measures were odds ratios (OR) and their 95% confidence intervals. Results: Among 36,483 PLWHIV, the frequency of CAD was 0.53% (n = 196). There was a high prevalence of impaired fasting glucose/diabetes mellitus (12.62%), overweight/obesity (27.79%), elevated LDL-c (86.69%), and hypertriglyceridemia (72.76%). Factors associated with CAD included male gender (OR: 2.01, 95% CI: 1.12-3.58), age ≥50 years (OR: 4.96, 95% CI: 3.29-7.45), lipoatrophy or lipodystrophy (OR 5.12, 95% CI: 1.12-23.33), AIDS-defining conditions (OR: 1.83, 95% CI: 1.07-3.12), obesity (OR: 2.95, 95% CI: 1.69-5.10), diabetes mellitus (OR: 2.50, 95% CI: 1.25-4.97), and renal impairment (OR: 3.15, 95% CI: 1.83-5.42). Conclusions: Traditional CAD risk factors are common in PLWHIV. There were traditional and disease-specific factors associated with increased odds of CAD. These findings may aid clinicians and decision-makers in reducing the impact of CAD in PLWHIV.

Implementation of a re-linkage to care strategy in patients with chronic hepatitis C who were lost to follow-up in Latin America.

To achieve WHO's goal of eliminating hepatitis C virus (HCV), innovative strategies must be designed to diagnose and treat more patients. Therefore, we aimed to describe an implementation strategy to identify patients with HCV who were lost to follow-up (LTFU) and offer them re-linkage to HCV care. We conducted an implementation study utilizing a strategy to contact patients with HCV who were not under regular follow-up in 13 countries from Latin America. Patients with HCV were identified by the international classification of diseases (ICD-9/10) or equivalent. Medical records were then reviewed to confirm the diagnosis of chronic HCV infection defined by anti-HCV+ and detectable HCV-RNA. Identified patients who were not under follow-up by a liver specialist were contacted by telephone or email, and offered a medical reevaluation. A total of 10,364 patients were classified to have HCV. After reviewing their medical charts, 1349 (13%) had undetectable HCV-RNA or were wrongly coded. Overall, 9015 (86.9%) individuals were identified with chronic HCV infection. A total of 5096 (56.5%) patients were under routine HCV care and 3919 (43.5%) had been LTFU. We were able to contact 1617 (41.3%) of the 3919 patients who were LTFU at the primary medical institution, of which 427 (26.4%) were cured at a different institutions or were dead. Of the remaining patients, 906 (76.1%) were candidates for retrieval. In our cohort, about one out of four patients with chronic HCV who were LTFU were candidates to receive treatment. This strategy has the potential to be effective, accessible and significantly impacts on the HCV care cascade.

Modeling the role of police corruption in the reduction of organized crime: Mexico as a case study.

Among all types of corruption, police corruption is probably the one that most directly hurts society, as those trusted with protecting the people either side with the criminals that victimize the citizens, or are themselves, criminals. However, both corruption and its effects are very difficult to measure quantitatively other than by perception surveys, but the perception that citizens have of this phenomenon may be different from reality. Using a simple agent-based model, we analyze the effect on crime rates as a result of both corruption and the perception of corruption within law-enforcement corporations. Our results show a phase transition in which crime can propagate across the population even when the majority of police officers are honest. We find that one of the parameters that strongly controls crime incidence is the probability that regular citizens become criminals. In contrast, other actions, such as arresting crime lords, or the amount of crime-associated money that is confiscated, have little impact on the long-term crime incidence. Our results suggest that in addition to combating corruption within law-enforcement institutions, to further reduce the incidence of crime, policymakers should strive to restore confidence in these institutions and the justice system.

Interaction Effect Between Hemoglobin and Hypoxemia on COVID-19 Mortality: an observational study from Bogotá, Colombia.

Purpose: We aimed to assess the effect of hemoglobin (Hb) concentration and oxygenation index on COVID-19 patients' mortality risk. Patients and Methods: We retrospectively reviewed sociodemographic and clinical characteristics, laboratory findings, and clinical outcomes from patients admitted to a tertiary care hospital in Bogotá, Colombia, from March to July 2020. We assessed exploratory associations between oxygenation index and Hb concentration at admission and clinical outcomes. We used a generalized additive model (GAM) to evaluate the observed nonlinear relations and the classification and regression trees (CART) algorithm to assess the interaction effects. Results: We included 550 patients, of which 52% were male. The median age was 57 years old, and the most frequent comorbidity was hypertension (29%). The median value of SpO2/FiO2 was 424, and the median Hb concentration was 15 g/dL. The mortality was 15.1% (83 patients). Age, sex, and SpO2/FiO2, were independently associated with mortality. We described a nonlinear relationship between Hb concentration and neutrophil-to-lymphocyte ratio with mortality and an interaction effect between SpO2/FiO2 and Hb concentration. Patients with a similar oxygenation index had different mortality likelihoods based upon their Hb at admission. CART showed that patients with SpO2/FiO2 < 324, who were less than 81 years with an NLR >9.9, and Hb > 15 g/dl had the highest mortality risk (91%). Additionally, patients with SpO2/FiO2 > 324 but Hb of < 12 g/dl and a history of hypertension had a higher mortality likelihood (59%). In contrast, patients with SpO2/FiO2 > 324 and Hb of > 12 g/dl had the lowest mortality risk (9%). Conclusion: We found that a decreased SpO2/FiO2 increased mortality risk. Extreme values of Hb, either low or high, showed an increase in the likelihood of mortality. However, Hb concentration modified the SpO2/FiO2 effect on mortality; the probability of death in patients with low SpO2/FiO2 increased as Hb increased.

Menstrual cycle disturbances after COVID-19 vaccination.

INTRODUCTION: After COVID-19 vaccination, women of reproductive age reported changes in their menstrual cycle. MATERIALS AND METHODS: A retrospective study was carried out after a survey on social networks that included women aged 18-41 years with normal cycles according to International Federation of Gynecology and Obstetrics and who were vaccinated (complete schedule for two doses, except J&J/Janssen or incomplete with a single dose). Women with following conditions were excluded: pregnant or lactating women; history of diseases that cause menstrual irregularities or early menopause: anorexia, bulimia, polycystic ovary syndrome, hypothyroidism, obesity, or low weight; hysterectomized or oophorectomized patients; and high performance athletes. RESULTS: Overall, 950 women completed the survey between July and September 2021. In total, 408 women met the inclusion criteria, and 184 reported the following characteristics: frequency (normal 43.47%, infrequent 25%, and frequent 31.53%), regularity (regular 51.08%, irregular 42.93%, and absent/amenorrhea 5.97%), duration (normal 65.21%, prolonged 26.08%, absent/amenorrhea 8.69%), and volume (heavy 41.84%, light 20.65%, and absent/amenorrhea 6.52%). CONCLUSIONS: SARS-CoV-2 infection and COVID-19 vaccination can influence the menstrual cycle and cause alterations.

Effectiveness of Telemedicine Compared with Standard Care for Patients with Rheumatic Diseases: A Systematic Review.

Objective: The aim of this study was to systematically review the evidence on the effectiveness of telemedicine compared to standard care for patients with rheumatic diseases. Methods: A search was performed in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews; for the gray literature, GREYNET databases and a snowball search were used. MeSH or Emtree terms. Three authors independently selected systematic reviews, randomized controlled trail (RCTs), or non-RCTs with patients with autoimmune or inflammatory rheumatic diseases, where telemedicine was compared with standard care. Effectiveness was measured in terms of disease activity, quality of life, and functional activity. The patients' satisfaction was also measured. The risk of bias was assessed by the Cochrane collaboration tool for RCTs and AMSTAR II for systematic reviews. Results: Four RCTs, one cross-out study, and five systematic reviews were included. The studies were conducted with rheumatoid arthritis patients, and one study involved patients with systematic lupus erythematosus. The interventions mainly involved teleconsultation and telemonitoring, with patient-reported outcomes (PROs) being compared with standard care. Four studies measured the effectiveness of telemedicine using PROs, in which three of the RCTs did not find differences in the clinical outcomes, and one found that telemedicine improved the remission of diseases, functional impairment, and radiographic joint damage progression. Two studies measured patient satisfaction with telemedicine and standard care without a significant difference between the groups. Conclusions: Despite heterogeneity between studies, the findings were remarkably consistent in demonstrating that there was no significant difference between the telemedicine group and the control group in terms of PROs and patient satisfaction. Patients should be offered the option of telemedicine to manage their diseases as part of health-care support. Further research is needed on the effectiveness of telemedicine in the long term for patients with rheumatic diseases.

2021 clinical practice guideline for the early detection, diagnosis, treatment, and monitoring of patients with axial spondyloarthritis. Colombian Association of Rheumatology / Guía de práctica clínica 2021 para la detección temprana, el diagnóstico, el tratamiento y el seguimiento de los pacientes con espondiloartritis axial. Asociación Colombiana de Reumatología

Abstract Introduction: Axial spondyloarthritis is a rheumatic condition affecting young patients with social and occupational consequences. Diagnosis delay is associated with functional impairment and impact on quality of life, requiring a multidisciplinary approach. Objective: To develop a set of recommendations based on the best available evidence for the early detection, diagnosis, treatment, and monitoring of adult patients with axial spondy-loarthritis. Methods: A working group was established, questions were developed, outcomes were graded, and a systematic search for evidence was conducted. A multidisciplinary panel of members was established (including patient representatives), minimizing bias in relation to conflicts of interest. The GRADE approach "Grading of Recommendations Assessment, Development and Evaluation" was used to assess the quality of the evidence as well as the direction and strength of recommendations. In total, 11 recommendations on diagnosis (n=2), pharmacological treatment (n=6), non-pharmacological treatment (n=2) and monitoring (n=1) are presented. Results: Sacroiliac joint radiography as the first diagnostic method, and the use of disease activity scales for patient monitoring (ASDAS or BASDAI), are recommended. Nonsteroidal anti-inflammatory drugs are the first treatment option; in case of intolerance or residual pain, acetaminophen or opioids are recommended. In patients with axial involvement, it is recommended not to use conventional disease-modifying antirheumatic drugs or systemic or local glucocorticoids. In patients with failure to non-steroidal anti-inflammatory drugs, anti-TNF or anti-IL17A are recommended. In those patients presenting with anti-TNF failure, starting an anti-IL17A is recommended. Exercise, physical and occupational therapy are recommended as part of treatment. It is recommended not to use unconventional therapies as the only treatment option. Conclusions: This set of recommendations provides an updated guideline for the diagnosis, treatment, and monitoring of patients with axial spondyloarthritis.

RESUMEN Introducción: La espondiloartritis axial es una enfermedad reumatológica que afecta a individuos jóvenes y tiene una gran repercusión sociolaboral. El retraso en el diagnóstico y el tratamiento se asocia con un mayor deterioro funcional y un impacto negativo en la calidad de vida, por lo que requiere un abordaje multidisciplinario. Objetivo: Desarrollar y formular un conjunto de recomendaciones específicas basadas en la mejor evidencia disponible para la detección temprana, el diagnóstico, el tratamiento y el seguimiento de los pacientes adultos con espondiloartritis axial. Métodos: Se configuró un grupo desarrollador, se formularon preguntas clínicas contestables, se graduaron los desenlaces y se realizó la búsqueda sistemática de la evidencia. El panel de la guía fue multidisciplinario (incluyendo representantes de los pacientes) y balanceado, minimizando el sesgo por conflictos de intereses. Se utilizó la aproximación Grading of Recommendations Assessment, Development and Evaluation (GRADE) para evaluar la calidad de la evidencia, al igual que la dirección y la fortaleza de las recomendaciones. Se presentan 11 recomendaciones relacionadas con diagnóstico (n = 2), tratamiento farmacológico (n = 6), tratamiento no farmacológico (n = 2) y seguimiento (n = 1). Resultados: Se recomienda la radiografía de articulaciones sacroilíacas como primer método diagnóstico, y el uso de escalas de actividad para el seguimiento de los pacientes (ASDAS o BASDAI). Los antiinflamatorios no esteroideos son la primera opción de tratamiento; en caso de intolerancia o dolor residual se recomienda acetaminofén u opioides. En pacientes con compromiso axial se recomienda abstenerse de utilizar medicamentos antirreumáticos modificadores de la enfermedad convencionales ni glucocorticoides sistémicos o locales. En pacientes con falla a los antiinflamatorios no esteroideos, se recomienda un anti-TNFα o un anti-IL17A. En pacientes con falla a anti-TNFα, se recomienda iniciar un anti-IL17A. El ejercicio y la terapia física y ocupacional se recomiendan como parte del tratamiento. Se recomienda no utilizar las terapias no convencionales como única opción de tratamiento. Conclusiones: Este conjunto de recomendaciones proporciona una guía actualizada sobre el diagnóstico y el tratamiento de la espondiloartritis axial.

2021 clinical practice guideline for the early detection, diagnosis, treatment, and monitoring of patients with axial spondyloarthritis. Colombian Association of Rheumatology.

BACKGROUND: Axial Spondyloarthritis is a rheumatic condition affecting young patients with social and occupational consequences. Diagnosis delay is associated with functional impairment and impact on quality of life, requiring a multidisciplinary approach. OBJECTIVE: To develop a set of recommendations based on the best available evidence for early detection, diagnosis, treatment and monitoring adult patients with axial spondyloarthritis. METHODS: A working group was established, questions were developed, outcomes were graded, and a systematic search for evidence was conducted. A multidisciplinary panel of members was established (including patient representatives), minimizing bias in relation to conflicts of interest. The GRADE approach "Grading of Recommendations Assessment, Development and Evaluation" was used to assess the quality of the evidence as well as the direction and strength of recommendations. In total, 11 recommendations with regard to diagnosis (n = 2), pharmacological treatment (n = 6), non-pharmacological treatment (n = 2) and monitoring (n = 1) are presented. RESULTS: Sacroiliac joint radiography as the first diagnostic method, and the use of disease activity scales for patient monitoring (ASDAS or BASDAI), are recommended. Nonsteroidal anti-inflammatory drugs are the first treatment option; in case of intolerance or residual pain, acetaminophen or opioids are recommended. In patients with axial involvement, it is recommended not to use conventional disease-modifying antirheumatic drugs or systemic or local glucocorticoids. In patients with failure to non-steroidal anti-inflammatory drugs, anti-TNF or anti-IL17A is recommended. In those patients presenting with anti-TNF failure, starting an anti-IL17A is recommended. Exercise, physical and occupational therapy are recommended as part of treatment. It is recommended not to use unconventional therapies as the only treatment option. CONCLUSIONS: This set of recommendations provides an updated guide on the diagnosis, treatment and monitoring of patients with axial spondyloarthritis.

Characteristics of Inflammatory Bowel Disease Compared to Other National Centers in Colombia / Características de la enfermedad inflamatoria intestinal con respecto a otros centros nacionales de Colombia

Abstract Introduction: Inflammatory bowel disease (IBD) is an immune-mediated disease whose incidence in Latin America has increased in recent years. Aim: To analyze the demographic and clinical characteristics of patients with IBD treated in a university hospital and present the epidemiological data compared to other centers in Colombia. Patients and methods: Descriptive study of patients with IBD (1996-2019) at the Hospital Universitario Fundación Santa Fe de Bogotá. Analysis of data from centers in Medellín, Cali, Bogotá, and Cartagena. Results: Of 386 patients, 277 presented with ulcerative colitis (UC), 102 with Crohn's disease (CD), and seven with unclassifiable colitis. IBD was more frequent in women (53 %). Mortality was less than 1 %. The involvement of UC was mainly pancolitis (42.6 %). The greater the extent of the disease, the higher the hospitalization and surgery rates (OR 3.70, P < 0.01). Thirteen percent of patients with UC received biologics. Compromise due to CD was mainly ileocolonic (43.6 %) and ileal (43.6 %). The predominant clinical pattern of CD was structuring (50%). Forty-five percent received biologicals and 56 % surgery. Primary sclerosing cholangitis (PSC) was found in 4 % of patients (n = 15). Two patients with PSC developed colorectal cancer (OR 4.18; p 0.008), while 13 patients with UC developed colon cancer and seven dysplastic changes. Three patients with CD developed colon cancer. Conclusions: The results were compared to other reference centers. We found similar trends in the clinical behavior and treatment of IBD, with higher hospitalization and surgery rates in our cases.

Resumen Introducción: la enfermedad inflamatoria intestinal (EII) es una enfermedad inmunomediada, cuya incidencia en Latinoamérica ha aumentado en los últimos años. Objetivo: analizar las características demográficas y clínicas de los pacientes con EII tratados en un hospital universitario y presentar los datos epidemiológicos con respecto a otros centros en Colombia. Pacientes y métodos: estudio descriptivo de pacientes con EII (1996-2019) en el Hospital Universitario Fundación Santa Fe de Bogotá. Análisis de datos de centros de Medellín, Cali, Bogotá y Cartagena. Resultados: de 386 pacientes, 277 presentaron colitis ulcerativa (CU), 102 enfermedad de Crohn (EC) y 7 colitis no clasificable. La EII fue más frecuente en mujeres (53 %). La mortalidad fue menor de 1 %. El compromiso de la CU fue principalmente la pancolitis (42,6 %). Entre mayor la extensión de la enfermedad, más alta fue la tasa de hospitalización y cirugías (OR 3,70; p < 0,01). El 13 % de los pacientes con CU recibió biológicos. El compromiso por la EC fue principalmente ileocolónico (43,6 %) e ileal (43,6 %). El patrón clínico predominante de la EC fue estenosante (50%). El 45 % recibió biológicos y 56% cirugía. La colangitis esclerosante primaria (CEP) se encontró en 4 % de los pacientes (n = 15). Dos pacientes con CEP desarrollaron cáncer colorrectal (OR 4,18; p 0,008), mientras que 13 pacientes con CU desarrollaron cáncer de colon y 7 cambios displásicos. 3 pacientes con EC desarrollaron cáncer de colon. Conclusiones: se compararon los resultados en relación con otros centros de referencia. Encontramos tendencias similares en el comportamiento clínico y en el tratamiento de la EII, con mayores tazas de hospitalizaciones y cirugías en nuestros casos.

2021 clinical practice guidelines for the diagnosis, treatment, and follow-up of patients with peripheral spondyloarthritis. Colombian Association of Rheumatology / Guía de práctica clínica 2021 para el diagnóstico, el tratamiento y el seguimiento de pacientes con espondiloartritis periférica. Asociación Colombiana de Reumatología

ABSTRACT Background: Peripheral spondylarthritis is a chronic Inflammatory disease whose clinical presentation is related to the presence of arthritis, enthesitis and/or dactylitis. This term is used interchangeably with some of its subtypes such as psoriatic arthritis, reactive arthritis, and undifferentiated spondyloarthritis. Objective: To develop and formulate a set of specific recommendations based on the best available evidence for the diagnosis, treatment, and monitoring of adult patients with peripheral spondyloarthritis. Methods: A working group was established, clinical questions were formulated, outcomes were graded, and a systematic search for evidence was conducted. The guideline panel was multidisciplinary (including patient representatives) and balanced. Following the for mal expert consensus method, the GRADE methodology "Grading of Recommendations Assessment, Development and Evaluation" was used to assess the quality of the evidence and generate the recommendations. The clinical practice guideline includes ten recommendations related to monitoring of disease activity (n = 1) and treatment (n = 9). Results: In patients with peripheral spondyloarthritis, the use of methotrexate or sulfasalazine as the first line of treatment is suggested, and local injections of glucocorticoids are conditionally recommended. In patients with failure to cDMARDs, an anti TNFα or an anti IL17A is recommended. In case of failure to bDMARDs, it is suggested to use another bDMARD or JAK inhibitor. In patients with peripheral spondylarthritis associated with inflammatory bowel disease, it is recommended to start treatment with cDMARDs; in the absence of response, the use of an anti TNFα over an anti-IL-17 or an anti-IL-12-23 is recom mended as a second line of treatment. In patients with psoriatic arthritis, the combined use of methotrexate with a bDMARD is conditionally recommended for optimization of dosing. To assess disease activity in Psoriatic Arthritis, the use of DAPSA or MDA is suggested for patient monitoring. Conclusions: This set of recommendations provides an updated guideline on the diagnosis and treatment of peripheral spondyloarthritis.

RESUMEN Antecedentes: La espondiloartritis periférica es una patología Inflamatoria crónica cuya presentación clínica está determinada por la presencia de artritis, entesitis y/o dactilitis. Este término se utiliza indistintamente con algunos de sus subtipos como artritis psoriásica, artritis reactiva y espondiloartritis indiferenciada. Objetivo: Desarrollar y formular un conjunto de recomendaciones específicas basadas en la mejor evidencia disponible para el diagnóstico, el tratamiento y el seguimiento de pacientes adultos con espondiloartritis periférica. Métodos: Se constituyó un grupo desarrollador, se formularon preguntas clínicas, se graduaron los desenlaces y se realizó la búsqueda sistemática de la evidencia. El panel de la guía fue multidisciplinario (incluyendo representantes de los pacientes) y balanceado. Siguiendo el método de consenso formal de expertos, se utilizó la metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) para para evaluar la calidad de la evidencia y generar las recomendaciones. La guía de práctica clínica incluye 10 recomendaciones: una sobre seguimiento de la actividad de la enfermedad y nueve sobre tratamiento. Resultados: En pacientes con espondiloartritis periférica se sugiere usar metotrexato o sulfasalazina como primera línea de tratamiento y se recomienda en forma condicional la inyección local de glucocorticoides. En los pacientes que fallan a cDMARDs, se recomienda iniciar un anti TNFα o un anti IL17A. Ante falla terapéutica a la primera línea con bDMARDs, se sugiere usar otro bDMARD o un inhibidor JAK. En pacientes con espondiloartritis periférica y enfermedad inflamatoria intestinal asociada, se recomienda iniciar tratamiento con cDMARDs; en ausencia de respuesta, se recomienda el uso de un anti TNFα sobre un anti IL-17 o un anti IL-12-23 como segunda línea de tratamiento. En pacientes con artritis psoriásica se recomienda, de forma condicional, el uso combinado de metotrexato con bDMARD para favorecer la optimización de la dosis de estos. Para evaluar la actividad de la enfermedad en artritis psoriásica, se sugiere el uso del DAPSA o MDA para el seguimiento de los pacientes. Conclusiones: Este conjunto de recomendaciones proporcionan una guía actualizada sobre el diagnóstico y el tratamiento de la espondiloartritis periférica.

Acrosomal alkalinization occurs during human sperm capacitation.

Mammalian sperm capacitation is a prerequisite for successful fertilization. Capacitation involves biochemical and physiological modifications of sperm as they travel through the female reproductive tract. These modifications prepare the sperm to undergo the acrosome reaction (AR), an acrosome vesicle exocytosis that is necessary for gamete fusion. Capacitation requires an increase in both intracellular calcium ([Ca2+]i) and pH (pHi). Mouse sperm capacitation is accompanied by acrosomal alkalinization and artificial elevation of the acrosome pH (pHa) is sufficient to trigger the AR in mouse and human sperm, but it is unknown if pHa increases naturally during human sperm capacitation. We used single-cell imaging and image-based flow cytometry to evaluate pHa during capacitation and its regulation. We found that pHa progressively increases during capacitation. The V-ATPase, which immunolocalized to the acrosome and equatorial segment, is mainly responsible for the acidity of the acrosome. It is likely that the regulation of V-ATPase is at least in part responsible for the progressive increase in pHa during capacitation. Acrosome alkalinization was dependent on extracellular HCO3- and Ca2+. Inhibition of the HCO3--dependent adenylyl cyclase and protein kinase A induced significant pHa changes. Overall, alkalinization of the acrosome may be a key step in the path toward the AR.

2021 clinical practice guidelines for the diagnosis, treatment, and follow-up of patients with peripheral spondyloarthritis. Colombian Association of Rheumatology.

BACKGROUND: Peripheral spondyloarthritis is a chronic inflammatory disease in which clinical presentation is related to the presence of arthritis, enthesitis and/or dactylitis. This term is used interchangeably with some of its subtypes such as psoriatic arthritis, reactive arthritis, and undifferentiated spondyloarthritis. OBJECTIVE: To develop and formulate a set of specific recommendations based on the best available evidence for the diagnosis, treatment and monitoring of adult patients with peripheral spondyloarthritis. METHODS: A working group was established, clinical questions were formulated, outcomes were graded, and a systematic search for evidence was conducted. The guideline panel was multidisciplinary (including patient representatives) and balanced. Following the formal expert consensus method, the GRADE methodology "Grading of Recommendations Assessment, Development and Evaluation" was used to assess the quality of the evidence and generate the recommendations. The Clinical Practice Guideline includes ten recommendations; related to monitoring of disease activity (n = 1) and treatment (n = 9). RESULTS: In patients with peripheral spondyloarthritis, the use of methotrexate or sulfasalazine as the first line of treatment is suggested, and local injections of glucocorticoids is recommended conditionally. In patients with failure to cDMARDs, an anti TNFα or an anti IL17A is recommended. In case of failure to bDMARDs, it is suggested to use another bDMARD or JAK inhibitor. In patients with peripheral spondyloarthritis associated to inflammatory bowel disease, it is recommended to start treatment with cDMARDs; in the absence of response, the use of an anti TNFα over an anti-IL-17 or an anti-IL-12-23 is recommended as a second line of treatment. In patients with psoriatic arthritis, the combined use of methotrexate with bDMARD is conditionally recommended for optimization of dosing. To assess disease activity in Psoriatic Arthritis, the use of DAPSA or MDA is suggested for patient monitoring. CONCLUSIONS: This set of recommendations provides an updated guide on the diagnosis and treatment of peripheral spondyloarthritis.

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.

BACKGROUND: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). PATIENTS AND METHODS: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. RESULTS: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. CONCLUSION: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.

Villous atrophy, an endoscopic and diagnostic challenge.

A 57-year-old female presented with a five-year history of non-bloody diarrhea, reaching 10 to 20 daily depositions without abdominal cramping and a weight loss of 25 kg. Past medical history was significant for rheumatoid arthritis treated with rituximab during the last six years. All her previous endoscopic and histological studies identified lymphocytic infiltration. Previously, she received treatment with rifaximin, cholestyramine, and loperamide without improvement.

Mutation profile of SARS-CoV-2 genome in a sample from the first year of the pandemic in Colombia.

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the etiopathogenic agent of COVID-19, a condition that has led to a formally recognized pandemic by March 2020 (World Health Organization -WHO). The SARS-CoV-2 genome is constituted of 29,903 base pairs, that code for four structural proteins (N, M, S, and E) and more than 20 non-structural proteins. Mutations in any of these regions, especially in those that encode for the structural proteins, have allowed the identification of diverse lineages around the world, some of them named as Variants of Concern (VOC) and Variants of Interest (VOI), according to the WHO and CDC. In this study, by using Next Generation Sequencing (NGS) technology, we sequenced the SARS-CoV-2 genome of 422 samples from Colombian residents, all of them collected between April 2020 and January 2021. We obtained genetic information from 386 samples, leading us to the identification of 14 new lineages circulating in Colombia, 13 of which were identified for the first time in South America. GH was the predominant GISAID clade in our sample. Most mutations were either missense (53.6%) or synonymous mutations (37.4%), and most genetic changes were located in the ORF1ab gene (63.9%), followed by the S gene (12.9%). In the latter, we identified mutations E484K, L18F, and D614G. Recent evidence suggests that these mutations concede important particularities to the virus, compromising host immunity, the diagnostic test performance, and the effectiveness of some vaccines. Some important lineages containing these mutations are the Alpha, Beta, and Gamma (WHO Label). Further genomic surveillance is important for the understanding of emerging genomic variants and their correlation with disease severity.

Mathematical model reveals that heterogeneity in the number of ion transporters regulates the fraction of mouse sperm capacitation.

Capacitation is a complex maturation process mammalian sperm must undergo in the female genital tract to be able to fertilize an egg. This process involves, amongst others, physiological changes in flagellar beating pattern, membrane potential, intracellular ion concentrations and protein phosphorylation. Typically, in a capacitation medium, only a fraction of sperm achieve this state. The cause for this heterogeneous response is still not well understood and remains an open question. Here, one of our principal results is to develop a discrete regulatory network, with mostly deterministic dynamics in conjunction with some stochastic elements, for the main biochemical and biophysical processes involved in the early events of capacitation. The model criterion for capacitation requires the convergence of specific levels of a select set of nodes. Besides reproducing several experimental results and providing some insight on the network interrelations, the main contribution of the model is the suggestion that the degree of variability in the total amount and individual number of ion transporters among spermatozoa regulates the fraction of capacitated spermatozoa. This conclusion is consistent with recently reported experimental results. Based on this mathematical analysis, experimental clues are proposed for the control of capacitation levels. Furthermore, cooperative and interference traits that become apparent in the modelling among some components also call for future theoretical and experimental studies.

Discrete Dynamic Model of the Mammalian Sperm Acrosome Reaction: The Influence of Acrosomal pH and Physiological Heterogeneity.

The acrosome reaction (AR) is an exocytotic process essential for mammalian fertilization. It involves diverse physiological changes (biochemical, biophysical, and morphological) that culminate in the release of the acrosomal content to the extracellular medium as well as a reorganization of the plasma membrane (PM) that allows sperm to interact and fuse with the egg. In spite of many efforts, there are still important pending questions regarding the molecular mechanism regulating the AR. Particularly, the contribution of acrosomal alkalinization to AR triggering physiological conditions is not well understood. Also, the dependence of the proportion of sperm capable of undergoing AR on the physiological heterogeneity within a sperm population has not been studied. Here, we present a discrete mathematical model for the human sperm AR based on the physiological interactions among some of the main components of this complex exocytotic process. We show that this model can qualitatively reproduce diverse experimental results, and that it can be used to analyze how acrosomal pH (pH a ) and cell heterogeneity regulate AR. Our results confirm that a pH a increase can on its own trigger AR in a subpopulation of sperm, and furthermore, it indicates that this is a necessary step to trigger acrosomal exocytosis through progesterone, a known natural inducer of AR. Most importantly, we show that the proportion of sperm undergoing AR is directly related to the detailed structure of the population physiological heterogeneity.