Non-Cirrhotic Portal Hypertension in Human Immunodeficiency Virus-Infected Patients: A New Challenge in Antiretroviral Therapy Era

Non-cirrhotic portal hypertension (NCPH) has been recently reported as a liver disease in Human Immunodeficiency Virus (HIV)-infected patients under antiretroviral therapy (ART). Combination of non-exclusive mechanisms has been described: primary endothelial damage of terminal portal veins induced by HIV or immunologic disorders, mitochondrial toxicity by didanosine and prothrombotic state. It is characterized by heterogeneous liver histological findings, frequently identified as nodular regenerative hyperplasia and clinical manifestations of portal hypertension with well-preserved liver function. We describe herein two HIV-infected patients with clinical picture suggestive of NCPH. Besides the case reports, we briefly address questions to apply to patient care in clinical practice

Meropenem antimicrobial stewardship program: clinical, economic, and antibiotic resistance impact

Background. There are few prospective studies with sufficient duration in time to evaluate clinical and antibiotic resistance impact of Antibiotic Stewardship Programs (ASP). Methods. Descriptive study between January-2012 to December-2017, pre-postintervention. An meropenem ASP was initiated in January 2015, in patients who started treatment with meropenem an infectious diseases physician performed treatment recommendations to prescribers. Prospective information was collected to evaluate adequacy of meropenem prescription to local guidelines and to compare results between cases with accepted or rejected intervention. Analysis was performed to verify variables associated with intervention acceptance and with any significant change in meropenem consumption, hospital-acquired multidrug-resistant (MDR) bloodstream infections (BSIs) and 30-day all-cause crude death in MDR BSIs. Results. Adequacy of meropenem prescription and de-escalation from meropenem treatment to narrower-spectrum antibiotic improved progressively over time, after ASP implementation (p<0.001). Interventions on prescription were performed in 330 (38.7%) patients without meropenem justified treatment, in 269 intervention was accepted and in 61 not. Intervention acceptance was associated with shorter duration of treatment, cost and inpatient days (p<0.05); intervention rejection was not associated with severity of patient. During the period 2015-2017, meropenem consumption decreased compared with 2012-2014 [Rate ratio (RR) 0.67; 95%CI: 0.58- 0.77, p<0.001]). Likewise decreased, hospital-acquired MDR BSIs rate (RR 0.63; 95%CI: 0.38-1.02, p=0,048) and 30-day all-cause crude death in MDR BSIs (RR 0.45; 95%CI: 0.14-1.24, p=0.09), coinciding in time with ASP start-up. Conclusions. The decrease and better use of meropenem achieved had a sustained clinical, economic and ecological impact, reducing costs and mortality of hospital acquired MDR BSIs

Long-term carbapenems antimicrobial stewardship program

Abstract: Objective. To evaluate clinical and antibiotic resistance impact of carbapenems stewardship programs. Methods: descriptive study, pre-post-intervention, between January 2012 and December 2019; 350-bed teaching hospital. Prospective audit and feedback to prescribers was carried out between January 2015 and December 2019. We evaluate adequacy of carbapenems prescription to local guidelines and compare results between cases with accepted or rejected intervention. Analysis of antibiotic-consumption and hospital-acquired multidrug-resistant (MDR) bloodstream infections (BSIs) was performed. Results: 1432 patients were followed. Adequacy of carbapenems prescription improved from 49.7% in 2015 to 80.9% in 2019 (p < 0.001). Interventions on prescription were performed in 448 (31.3%) patients without carbapenem-justified treatment, in 371 intervention was accepted, in 77 it was not. Intervention acceptance was associated with shorter duration of all antibiotic treatment and inpatient days (p < 0.05), without differences in outcome. During the period 2015–2019, compared with 2012–2014, decreased meropenem consumption (Rate Ratio 0.58; 95%CI: 0.55–0.63), candidemia and hospital-acquired MDR BSIs rate (RR 0.62; 95%CI: 0.41–0.92, p = 0.02), and increased cefepime (RR 2; 95%CI: 1.77–2.26) and piperacillin-tazobactam consumption (RR 1.17; 95%CI: 1.11–1.24), p < 0.001. Conclusions: the decrease and better use of carbapenems achieved could have clinical and ecological impact over five years, reduce inpatient days, hospital-acquired MDR BSIs, and candidemia, despite the increase in other antibiotic-consumption

Characterization of chronic HCV infection in Northwest Spain: impact of the treatment strategic plan of the Spanish National Health Service on HCV cure

[Abstract] The aim of the study was to characterize HCV infection in Northwest Spain and assess the impact of the Spanish Strategic Plan to cure HCV infection. Overall, 387 patients were included (60.9% HIV/HCV coinfected and 28.2% cirrhotic). Of these, 72.9% of patients that were recognized as priority for HCV treatment according to the Spanish Strategic Plan (≥F2, transplant or extrahepatic manifestations), initiated treatment during 2015. Globally, SVR12 was achieved in 96.5% of patients. The implementation of the Spanish Strategic Plan has been critical to advance in HCV cure, but 27.1% of priority patients still remain awaiting HCV treatment initiation.Instituto de Salud Carlos III; CPII14/00014Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/02266Instituto de Salud Carlos III; CM15/00233Instituto de Salud Carlos III; FI14/0055

Determinants of long-term survival in late HIV presenters : The prospective PISCIS cohort study

Late HIV diagnosis (i.e CD4≤350 cells/µL) is associated with poorer outcomes. However, determinants of long-term mortality and factors influencing immune recovery within the first years after antiretroviral treatment (ART) initiation are poorly defined. From PISCIS cohort, we included all HIV-positive adults, two-year survivors after initiating ART between 2005-2019. The primary outcome was all-cause mortality according to the two-year CD4 count. We used Poisson regression. The secondary outcome was incomplete immune recovery (i.e., two-year CD4500 cells/µL, reference population). Overall, 113 patients (4·2%) died. Mortality was higher among LP with two-year CD4 count 200-500 cells/µL (aMRR 1·95[95%CI:1·06-3·61]) or 500 cells/µL, regardless of being initially LP or non-LP (aMRR 1·05[0·50-2·21]). Mortality rates within each two-year CD4 strata were not affected by the initial CD4 count at ART initiation (test-interaction, p = 0·48). The stronger factor influencing immune recovery was the CD4 count at ART initiation. First-line integrase-inhibitor-(INSTI)-based regimens were associated with reduced mortality compared to other regimens (aMRR 0·54[0·31-0·93]) and reduced risk of incomplete immune recovery in LP (aOR 0·70[0·52-0·95]). Two-year immune recovery is a good early predictor of long-term mortality in LP after surviving the first high-risk 2 years. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-LP. INSTI-based regimens were associated with higher rates of successful immune recovery and better survival compared to non-INSTI regimens. Southern-Denmark University, Danish AIDS-foundation, and Region of Southern Denmark

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Experiencias en el aula: tercer encuentro de prácticas pedagógicas innovadoras.

Experiencias de profesores en su quehacer en los distintos ambientes de aprendizaje presenciales y a distancia.Para el Centro de Excelencia Docente aeiou constituye un honor presentar la publicación del Tercer Encuentro de Prácticas Pedagógicas Innovadoras en el que se destacan cuarenta trabajos de profesores de UNIMINUTO provenientes de diferentes sedes. Con este encuentro son ya tres que bajo la dirección de aeiou los profesores han compartido su quehacer en los distintos ambientes de aprendizaje presenciales y a distancia. Cada año el Centro de Excelencia Docente invita a los profesores a participar en este evento, para el 2108 además de la inscripción voluntaria por parte de cada profesor, se invitó al estudiantado a que postularan a sus profesores que consideraban eran innovadores y creativos en el cumplimiento de su función docente y se obtuvo una respuesta importante por parte de los estudiantes, que para algunos profesores resultó sorpresiva porque quizás no habían considerado que el trabajo que hacían en su ambiente de aprendizaje era diferente, fuera de lo común. Luego de una evaluación de jurados nacionales e internacionales de las prácticas presentadas y de la realización del evento, que tuvo como novedad hacerlo de forma simultánea en cuatro sedes donde UNIMINUTO tiene presencia: Buga, Ibagué, Pereira y Bogotá, se comparte la presente publicación para tener como referencia y evidencia el trabajo que los profesores hacen a diario

Impacto clínico das actuais combinacións de fármacos antirretrovirais de inicio sobre a viremia non suprimida e marcadores de inflamación, na infección polo VIH.

Background. Antiretroviral therapy (ART) has allowed a dramatic reduction in Human Immunodeficiency Virus (HIV)-related morbidity and mortality. Current ART combinations effectively suppress HIV replication for a long-time and preserve the immune system of the patients. However, the long-term efficacy of ART could be jeopardized in subjects with low-level viremia (LLV) and residual viremia (RV) which could be related with incomplete HIV suppression. There are some incompletely understood issues regarding the LLV and RV definitions and measurements as well as the interpretation of the impact on subsequent virological failure and potential emergence of drug resistance mutations developed under the selective pressure of a drug in the absence of full viral suppression. Objectives. The aim of this project is to prospectively evaluate the impact of different drug combinations on rates of virological non-suppression and cytokines dynamics, among HIV-infected patients who start ART. Study population and procedure. Observational study. Data and samples of patients will be retrieved from a nationwide cohort and processed at the Biobank of Galicia Sur Health Research Institute, in Vigo. Expected results. The results obtained in this study could identify determinants and drugs associated with virological non-suppression, resulting in prevention of the development of drug resistance mutations during ART.Introducción. La terapia antirretroviral (TAR) ha permitido una reducción significativa de la morbilidad y mortalidad asociada al Virus de la Inmunodeficiencia Humana (VIH). Las combinaciones actuales de TAR suprimen la replicación del VIH de forma eficaz durante un período de tiempo prolongado y preservan el sistema inmune de los pacientes. Sin embargo, la eficacia a largo plazo del TAR podría verse comprometida en sujetos con viremia de bajo nivel (LLV) y viremia residual (RV), que podrían estar asociadas a una incompleta supresión del VIH. Hay algunos aspectos controvertidos en relación a las definiciones y mediciones de LLV y RV, así como la interpretación del impacto en el fracaso virológico y la potencial emergencia de mutaciones de resistencia a fármacos, desarrollada bajo la presión selectiva del fármaco en ausencia de supresión viral completa. Objetivos. El objetivo de este proyecto es evaluar prospectivamente el impacto de diferentes combinaciones de fármacos antirretrovirales sobre las tasas de viremia no suprimida y dinámica de citoquinas, entre los pacientes infectados por el VIH que empiezan TAR. Población de estudio, material y métodos. Estudio observacional. Datos y muestras de pacientes serán obtenidos de una cohorte nacional y procesados en el Biobanco del Instituto de Investigación Sanitaria Galicia Sur en Vigo. Resultados esperados. Los resultados obtenidos en el estudio podrían identificar determinantes y fármacos antirretrovirales asociados con viremia no suprimida, contribuyendo a la prevención del desarrollo de mutaciones de resistencia asociadas a fármacos durante el TAR.Introdución. A terapia antirretroviral (TAR) permitiu unha redución significativa da morbilidade e mortalidade asociada ó Virus da Inmunodeficiencia Humana (VIH). As combinacións actuais de TAR suprimen a replicación do VIH de forma eficaz durante un período de tempo prolongado e preservan o sistema inmune dos pacientes. Non obstante, a eficacia a longo prazo do TAR podería verse comprometida en suxeitos con viremia de baixo nivel (LLV) e viremia residual (RV), que poderían estar asociadas a unha incompleta supresión do VIH. Hai algúns aspectos controvertibles en relación ás definicións e medición de LLV e RV, así como á interpretación do impacto no fallo virolóxico e a potencial emerxencia de mutacións de resistencia a fármacos, desenvolta baixo a presión selectiva do fármaco en ausencia de supresión viral completa. Obxectivos. O obxectivo deste proxecto é avaliar prospectivamente o impacto de diferentes combinacións de fármacos antirretrovirais sobre as taxas de viremia non suprimida e a dinámica de citoquinas, entre os pacientes infectados polo VIH que empezan TAR. Poboación de estudo, material e métodos. Estudo observacional. Datos e mostras de pacientes serán obtidos dunha cohorte nacional, e procesados no Biobanco do Instituto de Investigación Sanitaria Galicia Sur en Vigo. Resultados esperados. Os resultados obtidos no estudo poderían identificar determinantes e fármacos antirretrovirais asociados con viremia non suprimida, contribuíndo á prevención do desenvolvemento de mutacións de resistencia asociadas a fármacos durante o TAR