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Background: HIV/AIDS progression is linked to vitamin D, which is regulated by several key cytochromes P450 (CYP). Single nucleotide polymorphisms (SNPs) in CYP genes influence vitamin D metabolism and serum levels. The objective of this study was to evaluate the association between CYP SNPs and the clinical AIDS progression in antiretroviral treatment (ART)-naïve HIV-infected patients. Methods: We performed a retrospective study in 661 ART-naïve HIV-infected patients who were stratified by their AIDS progression pattern [181 long-term nonprogressors (LTNPs), 332 moderate progressors, and 148 rapid progressors (RPs)]. Four CYP SNPs (CYP2R1 rs10500804, CYP2R1 rs1993116, CYP27B1 rs10877012, and CYP24A1 rs6013897) were genotyped using Agena Bioscience's MassARRAY platform. Correction for multiple testing was performed using the false discovery rate (Benjamini-Hochberg procedure). Results: The adjusted regression showed a significant association only for CYP27B1 rs10877012 SNP. When analyzing all HIV patients, the rs10877012 T allele was protective against AIDS progression (ordinal outcome) under the dominant [adjusted odds ratio (aOR) = 0.69; P = 0.021) and additive (aOR) = 0.75; P = 0.025] inheritance models. When analyzing LTNPs versus RPs, the rs10877012 T allele also showed a significant protective association under the dominant (aOR = 0.45; P = 0.004) and additive (aOR = 0.54; P = 0.008) inheritance models. P values remained significant after correcting by multiple comparisons only for the comparison of LTNPs versus RPs (extreme phenotypes). Conclusions: The CYP27B1 rs10877012 T allele was linked to non-AIDS progression in ART-naïve HIV-infected patients. The rs10877012 SNP seems to have an impact on the clinical AIDS progression, possibly modifying vitamin D levels, which could be relevant for the pathogenesis of HIV infection. This work has been (partially) funded by the RD16/0025/0019 and RD16CIII/0002/0002, projects as part of Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (2013-2016) and cofinanced by Instituto de Salud Carlos III (ISCIII-Subdirección General de Evaluación) and Fondo Europeo de Desarrollo Regional (FEDER), RETIC PT17/0015/0042, Fondo de Investigación Sanitaria (FIS) (grant number PI16/01863, PI17/01115, PI17CIII/00003), EPIICAL Project and Comunidad de Madrid (B2017/BMD-3703). CIBER-BBN is an initiative funded by the VINational R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, the Consolider Program, and CIBER Actions and financed by ISCIII with assistance from the European Regional Development Fund. This work has been supported partially by a EUROPARTNER: Strengthening and spreading international partnership activities of the Faculty of Biology and Environmental Protection for interdisciplinary research and innovation of the University of Lodz Programme: NAWA International Academic Partnership Programme. This article/publication is based upon work from COST Action CA 17140 "Cancer Nanomedicine from the Bench to the Bedside" supported by COST (European Cooperation in Science and Technology). AFR and MAJS are supported by “Instituto de Salud Carlos III” [grant number CP14/0010and CP17CIII/00007, respectivelly].Programa de Investigación de la Consejería de Sanidad de la Comunidad de Madrid to JLJ. Sí

BackgroundSince December 2019, the COVID-19 pandemic has changed the concept of medicine. This work aims to analyze the use of antibiotics in patients admitted to the hospital due to SARS-CoV-2 infection.MethodsThis work analyzes the use and effectiveness of antibiotics in hospitalized patients with COVID-19 based on data from the SEMI-COVID-19 registry, an initiative to generate knowledge about this disease using data from electronic medical records. Our primary endpoint was all-cause in-hospital mortality according to antibiotic use. The secondary endpoint was the effect of macrolides on mortality.ResultsOf 13,932 patients, antibiotics were used in 12,238. The overall death rate was 20.7% and higher among those taking antibiotics (87.8%). Higher mortality was observed with use of all antibiotics (OR 1.40, 95% CI 1.21–1.62;p p ConclusionsBacterial co-infection was uncommon among COVID-19 patients, yet use of antibiotics was high. There is insufficient evidence to support widespread use of empiric antibiotics in these patients. Most may not require empiric treatment and if they do, there is promising evidence regarding azithromycin as a potential COVID-19 treatment.

Robust polyclonal humoral immune responses have the potential to generate a diverse set of antibodies to neutralize and eliminate viruses such as SARS-CoV-2 and protect against transmission, re-infection and the evolution of variants that evade immunity. CD73 is present on subsets of human B and T cells where it plays a role in lymphocyte activation and migration. CD73 also functions as an ectoenzyme that converts AMP into immunosuppressive adenosine. We have developed a humanized anti-CD73 antibody, mupadolimab (CPI-006), that blocks CD73 enzymatic activity and activates CD73POSB cells, thereby inducing differentiation into plasmablasts, immunoglobulin class switching, and antibody secretion independent of the adenosine modulatory activity. These effects suggest mupadolimab may enhance the magnitude, diversity, and duration of anti-viral responses in patients with COVID-19. This hypothesis was tested in a dose escalation phase 1 trial in 29 hospitalized patients with COVID-19. Single doses of 0.3 mg/kg – 5 mg/kg mupadolimab were well tolerated with no drug related adverse events. Doses greater than 0.3 mg/kg resulted in rapid generation of IgG and IgM to SARS-CoV-2 significantly above titers measured in convalescent controls, with elevated IgG titers sustained for more than 6 months beyond presentation of symptoms. Based on these findings, a randomized double-blind, placebo-controlled Phase 3 study in hospitalized patients was initiated. The primary endpoint was proportion of patients alive and free from respiratory failure within 28 days. This trial was discontinued early during the period of waning COVID-19 incidence after enrolling 40 patients. Although underpowered, results from this trial suggest improvement in the primary and key secondary endpoints in patients treated with single doses of 2 mg/kg and 1 mg/kg compared to placebo. The presumed mechanism of action, stimulation of B cells, may represent a novel approach to immunotherapy of COVID-19 and other viral infections.

Summary Background Many Spanish hospitals converted scheduled in-person visits to telephone visits during the COVID-19 lockdown. There is scarce information about the performance of those visits. Aim To compare telephone visits during the COVID-19 lockdown period with previous in-person visits. Design Retrospective descriptive study. Methods Telephone visits from 15 March to 31 May 2020 were compared with in-person visits during the same period in 2019. Main measures The proportions of both groups were compared in term of failure to contact patient, requested diagnostic tests/referrals, discharges, admissions and emergency visits within 30–60 days. A sample of patients, and all participating physicians completed surveys. Z-score test was used (statistical significance P Results A total of 5602 telephone visits were conducted. In comparison to in-person visits, telephone visits showed higher rates of visit compliance (95.9% vs. 85.2%, P Conclusions During health emergencies, previously scheduled outpatient in-person visits can be converted to telephone visits, reducing absenteeism, increasing the rate of discharges and reducing ancillary tests and referrals without increasing the rate of hospital admissions or emergency department visits.

Human immunodeficiency virus (HIV) remains incurable due to latent viral reservoirs established in non-activated CD4 T cells that cannot be eliminated via antiretroviral therapy. Current efforts to cure HIV are focused on identifying drugs that will induce viral gene expression in latently infected cells, commonly known as latency reversing agents (LRAs). Some drugs have been shown to reactivate latent HIV but do not cause a reduction in reservoir size. Therefore, finding new LRAs or new combinations or increasing the round of stimulations is needed to cure HIV. However, the effects of these drugs on viral rebound after prolonged treatment have not been evaluated. In a previous clinical trial, antiretroviral therapy intensification with maraviroc for 48 weeks caused an increase in residual viremia and episomal two LTR-DNA circles suggesting that maraviroc could reactivate latent HIV. We amended the initial clinical trial to explore additional virologic parameters in stored samples and to evaluate the time to viral rebound during analytical treatment interruption in three patients. Maraviroc induced an increase in cell-associated HIV RNA during the administration of the drug. However, there was a rapid rebound of viremia after antiretroviral therapy discontinuation. HIV-specific T cell response was slightly enhanced. These results show that maraviroc can reactivate latent HIV in vivo but further studies are required to efficiently reduce the reservoir size.

We describe an unusual clinical association of disseminated histoplasmosis with reactive hemophagocytic syndrome. We report the case of a new HIV-positive patient with reconstitution inflammatory syndrome like reactive hemophagocytic syndrome associated with disseminated histoplasmosis. We describe the clinical case, the procedures performed, the treatment provided and the patient's evolution. A figure of liver biopsy Grocott's silver methenamine stain that shows lots of uniform ovoid yeasts in portal spaces' macrophages that supports the diagnosis of disseminated histoplasmosis in our case.

We conducted a retrospective observational study to demonstrate that switching to insulin degludec from other long-acting insulins reduces the risk of hypoglycaemia events and improves glycaemic control in patients with type 2 diabetes and stage 2-3B chronic kidney disease.

Resumen Fundamento y objetivo La bacteriemia oculta representa un 3% de los hemocultivos extraidos en Urgencias. En la mayor parte de los casos se desconoce la evolucion posterior, por lo que deben implementarse estrategias para recuperar estos pacientes. El objetivo del presente estudio es describir los resultados tras la implantacion de un programa de intervencion sobre pacientes con bacteriemia dados de alta desde el Servicio de Urgencias. Pacientes y metodo Se describen los resultados de un programa de intervencion precoz sobre pacientes con bacteriemia dados de alta en el Servicio Urgencias e implantado en la actividad diaria del Hospital Costa del Sol de Marbella (Malaga). Se analizaron las caracteristicas epidemiologicas, microbiologicas, el indice de comorbilidad de Charlson, el indice de bacteriemia de Pitt y la mortalidad a 30 dias. Resultados Durante 15 meses se localizaron 90 pacientes. La mediana de edad fue de 67 anos. Hubo 54 varones (60%). El lugar de adquisicion fue comunitario en 51 casos (56,6%) y el microorganismo mas frecuentemente involucrado fue Escherichia coli, con 31 casos (34,4%). La mediana del indice de Charlson y de bacteriemia de Pitt fue de 1. Treinta y ocho casos requirieron ingreso hospitalario (42,2%). El indice de Pitt > 1 y el cambio de tratamiento fueron las variables relacionadas con la necesidad de ingreso. Un paciente fallecio (1,2%) y 6 no pudieron ser localizados (6,6%). Conclusiones La implantacion de programas de identificacion de pacientes con bacteriemia remitidos a domicilio permite la recuperacion precoz de aquellos que precisan ingreso hospitalario y la optimizacion del tratamiento antibiotico. En nuestra serie, la mortalidad tras la intervencion precoz es muy baja (1,2%).

Regarding the article by Han et al. (1), we would like to add the following comments. As the article points out, diagnosis, control objectives, and therapy in the patient with HIV and type 2 diabetes are similar to those in the non-HIV patient (2). At present the approach in patients with HIV and type 2 diabetes who are overweight or obese should be treatment with antidiabetic medications that, in addition to improving …

Introducción En España algunos pacientes con VIH no reciben tratamiento antirretroviral (TAR), aun teniendo indicaciones para ello. Nuestro objetivo es identificar las barreras de inicio del TAR en pacientes con indicación para recibirlo. Métodos Encuesta transversal en 19 hospitales en España en 2012, incluyendo todos los pacientes que no recibían tratamiento y tenían al menos una indicación según las recomendaciones de Gesida/2011. Las posibles barreras se agruparon así (categorías no excluyentes): a) el médico considera que la indicación no es absoluta; b) el paciente no quiere iniciarlo; c) el médico considera que debe iniciarlo pero existe alguna limitación o contraindicación; y d) el paciente tiene viremia indetectable en ausencia de tratamiento. Resultados Se incluyeron 256 pacientes de los 784 programados; 84% hombres, mediana de edad 39 años; 57% homosexuales, 24% heterosexuales, 16% UDI. Mediana de tiempo desde el diagnóstico: 3 años, CD4: 501 células/mm3, carga viral 4,4 log. Indicaciones de TAR más frecuentes: CD4

In Spain, HIV treatment guidelines are well known and generally followed. However, in some patients there are no plans to initiate ART despite having treatment indications. The current barriers to ART initiation are presented.A cross-sectional survey including every HIV infected patient in care in 19 hospitals across Spain in 2012, with ≥1 indication to start ART according to 2011 national treatment guidelines, who had not been scheduled for ART initiation. Reasons for deferring treatment were categorized as follows (non-exclusive categories): a) The physician thinks the indication is not absolute and prefers to defer it; b) The patient does not want to start it; c) The physician thinks ART must be started, but there is some limitation to starting it, and d) The patient has undetectable viral load in absence of ART.A total of 256 patients, out of 784 originally planned, were included. The large majority (84%) were male, median age 39 years, 57% MSM, 24% heterosexuals, and 16% IDUs. Median time since HIV diagnosis was 3 years, median CD4 count, 501 cells/mm3, median viral load 4.4 log copies/ml. Main ART indications were: CD4 count500 cells/mm(3), 48%; having an uninfected sexual partner, 28%, and hepatitis C coinfection, 23%. Barriers due to, the physician, 55%; the patient, 28%; other limitations, 23%; and undetectable viral load, 6%.The majority of subjects with ART indication were on it. The most frequent barriers among those who did not receive it were physician-related, suggesting that the relevance of the conditions that indicate ART may need reinforcing.

The proportion of asymptomatic individuals infected by influenza AH1N1v varies depending on the studies. Health personnel were exposed to the AH1N1v virus due to their professional activity, thus an high seroprevalence to the virus could be expected in the absence of symptomatology. The objective of this study was to determine the prevalence of asymptomatic individuals serologically positive for influenza AH1N1v virus.A cohort based prospective study on hospital staff was proposed according to an hypothetic decreasing gradient of exposure to the virus, from emergency personnel to medical and surgical areas, and auxiliary staff other than emergency personnel. Serum sample from each participant was taken in September-October, 2009, November-December, 2009, and in April-May, 2010; and a health questionnaire was simultaneously filled out. Specific antibodies against influenza AH1N1v were detected by hemagglutination inhibition test. Eighteen hospitals (1,371 individuals) participated in the study.Health questionnaire and serological results from four hospitals are available. A variable proportion of non vaccinated individuals showed positive serology (5.6-83%). Only 19.4% of subjects received vaccine, with a variable rate of positive serology (18.8-64.7%). Positive serology was significantly lower in non medical participants. In addition, vaccine coverage was higher in medical personnel than in the rest of professional categories.There was a variable percentage of influenza AH1N1v seropositive individuals who had not suffered clinical symptomatology. This serological study detects differences on vaccine efficacy.

espanolIntroduccion: describir un cuadro poco habitual como es la leishmaniasis visceral con afectacion colonica. Caso clinico: presentamos el caso de un paciente VIH positivo con leishmaniasis visceral. Se describe el caso clinico, con los procedimientos realizados, el tratamiento y su evolucion. Se adjunta tabla comparativa de los casos publicados de leishmaniasis con afectacion de colon. Discusion: la afectacion intestinal en la leishmaniasis visceral es un proceso infrecuente, que debe incluirse en el diagnostico diferencial en todo paciente inmunodeprimido con clinica de diarrea y que requiere un diagnostico precoz y tratamiento adecuado, del que depende el pronostico del paciente. EnglishBackground: To describe an unusual clinical presentation of visceral leishmaniasis affecting the colon. Case report: We report the case of an HIV-positive patient with visceral leishmaniasis. We describe the clinical case, the procedures performed, the treatment provided and the patient’s evolution. A comparative table of previously reported similar cases is shown. Discussion: Visceral leishmaniasis with intestinal involvement is an uncommon process. Nevertheless, this possibility should be taken into consideration in the differential diagnosis of immunosuppressed patients with symptoms of diarrhea, as a favorable prognosis depends on early diagnosis and appropriate treatment.