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MPOX (monkeypox) is a zoonotic viral disease, endemic in some Central and West African countries. However, in May 2022, cases began to be reported in non-endemic countries, demonstrating community transmission. Since the beginning of the outbreak, different epidemiological and clinical behaviors have been observed. We conducted an observational study at a secondary hospital in Madrid to characterize suspected and confirmed cases of MPOX epidemiologically and clinically. Besides the general descriptive analysis, we compared data between HIV-positive and HIV-negative subjects; 133 patients were evaluated with suspected MPOX, of which 100 were confirmed. Regarding positive cases, 71.0% were HIV positive, and 99.0% were men with a mean age of 33. In the previous year, 97.6% reported having sex with men, 53.6% used apps for sexual encounters, 22.9% practiced chemsex, and 16.7% went to saunas. Inguinal adenopathies were significantly higher in MPOX cases (54.0% vs. 12.1%, p < 0.001), as the involvement of genital and perianal area (57.0% vs. 27.3% and 17.0% vs. 1.0%, p = 0.006 and p = 0.082 respectively). Pustules were the most common skin lesion (45.0%). In HIV-positive cases, only 6.9% had a detectable viral load, and the mean CD4 count was 607.0/mm3. No significant differences were observed in the disease course, except for a greater tendency towards the appearance of perianal lesions. In conclusion, the MPOX 2022 outbreak in our area has been related to sexual intercourse among MSM, with no severe clinical cases nor apparent differences in HIV and non-HIV patients.

Background Dolutegravir-based dual therapies for treating people living with HIV (PLHIV) are strategies strongly recommended in several practice guidelines. The safety and efficacy combination of Dolutegravir (DTG) plus 3TC as a switching strategy in virologically suppressed patients was demonstrated in the TANGO study. Wide multicenter real life data supporting this treatment is needed. The aim of the current study was to describe the efficacy in terms of immunovirological outcomes in patients treated with this antiretroviral combination. Methods From November 1st 2020 to August 1st 2021, data from 1062 PLHIV collected from 13 Spanish institutions were recorded in a multicenter, retrospective study; After discarding cases in which relevant variables were missing, finally 694 cases underwent statistical analysis. Inclusion criteria were age >18 years, and to receive treatment with DTG/3TC as a switch strategy. Immunovirological impact of this strategy ( CD4+, CD8+ and CD4+/CD8+ cell count, as well as HIV plasma viral load through weeks 24, 48 and 96 of follow up) was evaluated using multivariable mixed models where the individual was considered as a random effect. Sex and age were added as demographic covariables. Results 78% of patients were men, 16% had been previously diagnosed of AIDS. Mean age was 48 years old. Mean CD4 T cell count nadir was 300 cell/ml (160-480). We found a significant increase in CD4+ counts at 24, 48 and 96 weeks after switching drug strategy. We also detected a small increase in the CD4+/CD8+ count rate at 48 and 96 weeks. No significant change was found in CD8+ count. No differences were found on behalf of sex, between backbone drugs (73% switched from a TDF/FTC backbone and 26.9% from ABC/3TC) or amongst the different third agents used (62% switched from integrase inhibitors). We identified a strong and negative effect of having AIDS in the CD4+ count. However, this effect did not interact with the effect of switching drug strategies. CD4, CD8 and CD4/CD8 after switch at 24, 48 and 96w Log OR Conclusion PLHIV who, being virologically suppressed, switched to dual therapy based on DTG/3TC, experienced a statistically significant increase of CD4+ T cell count at weeks 24, 48 and 96, as well as an increase in CD4/CD8 T cell ratio, as well as high efficacy in terms of viral replication suppression, independently of the stage of HIV infection. Disclosures Luis Buzón-Martín, MD, ViiV, GILEAD, Jannsen, MSD: Lecture fees Carlos Dueñas Gutierrez, MD, ViIV, GILEAD, Jannsen, MSD: Lecture fees Jesús Troya, Staff, ViiV, GILEAD, Jannsen, MSD: Lecture fees.

Our objective was to evaluate the effectiveness of initiated or reinitiated antiretroviral therapy (ART) in HIV-positive active drug users receiving integrated HIV and addiction care in a harm reduction setting. We performed a study of HIV-positive persons who use drugs (PWUD) in a harm reduction unit in Madrid, Spain. Participants received HIV care integrated into addiction care and received at least one dose of observed ART based on medication-assisted treatment between January 2013 and December 2019. Individuals newly diagnosed with HIV (n = 13) had a greater median CD4 cell count at baseline were less likely to be late presenters, had a greater CD4 cell count increase, and were less likely to have AIDS in comparison to those who were aware of their HIV status (n = 87) at initiation or reinitiation of ART. The overall VS was 73% in the intention-to-treat (ITT) analysis and 92.4% in the modified intention-to-treat (mITT) analysis. People who were engaged in OST, people with >90% adherence to ART, and older people were positively associated with VS in the multivariate analysis. An HIV care model integrated into a harm reduction facility demonstrated a high uptake of HIV treatment, retention in care, improvement in adherence, and achievement of VS.

Con el texto que hoy se presenta, denominado PROCEDIMIENTOS, MANIOBRAS Y TÉCNICAS QUIRÚRGICAS EN URGENCIAS, se pretende hacer una contribución real a nivel teórico como herramienta de enseñanza – aprendizaje que discurren estrictamente sobre contenidos específicos que contribuyen al conocimiento y comprensión de diversas técnicas quirúrgicas, pruebas de diagnóstico y maniobras en la atención del parto en presentación pelviana. No se trata de un tratado sobre todas las técnicas quirúrgicas, por lo cual, es posible que existan facetas que se escapen o se queden cortas. La información podría ser interminable debido a la vastedad existente de la misma, por ello, se insta a los usuarios a continuar leyendo, estudiando, aprisionando información disponible en textos, investigaciones y artículos científicos, tesis de grado, etc., la cual les permita nutrir cada día más el conocimiento en tan importante área de la medicina y específicamente de la Cirugía General. Las técnicas quirúrgicas son los procedimientos de manipulación mecánica de las estructuras anatómicas con un fin médico, bien sea diagnóstico, terapéutico o pronóstico. Este libro está enfocado básicamente al conocimiento sobre algunos procedimientos diagnósticos, maniobra obstétrica y técnicas quirúrgicas, el cual está dirigido a estudiantes y profesionales de la salud.

Background Although switching antiretroviral therapy (ART) in people with human immunodeficiency virus experiencing insomnia due to dolutegravir-related neurotoxicity is well founded upon evidence, there is a lack of proof in regard to the outcome of stopping dolutegravir-based ART in people without insomnia but reporting poor sleep quality. Methods This is a randomized, multicenter, open-label study to evaluate the reversibility of patient-reported sleep disturbances in patients on dolutegravir/lamivudine/abacavir without insomnia after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants were randomized to switch ART at baseline or at week 4 and then completed 8 weeks of darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Our primary objective was to compare changes in sleep quality between arms at week 4. Secondary objectives were to compare changes in mood and neuropsychiatric symptoms (NS) at week 4 and 4 and 8 weeks after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants completed a survey, including the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression scale (HADS), and specific questions to explore NS, at each visit to assess those objectives. Results We included 72 participants. The results show that study arms were similar at baseline; however, at week 4, PSQI scores remained unchanged with dolutegravir/lamivudine/abacavir, whereas patients improved significantly after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Similar differences between arms were also observed in HADS and NS changes. At weeks 4 and 8 after all participants switched to darunavir/cobicistat/emtricitabine/tenofovir alafenamide, we have observed significant improvements in PSQI and HAD scores and in NS. Conclusions In patients reporting subclinical sleep disturbances without insomnia, switching from dolutegravir/lamivudine/abacavir to darunavir/cobicistat/emtricitabine/tenofovir alafenamide was associated with better sleep quality and improvements in mood and NS.

Chagas disease is an emerging infectious disease in Europe and other non-endemic areas, mainly owing to migration from endemic areas. We aimed at investigating the value of advanced echocardiography (ECHO) and cardiac magnetic resonance (CMR) in patients newly diagnosed with Chagas disease to compare findings with those of electrocardiogram (ECG) and conventional ECHO and thus detecting cardiac abnormalities. We included consecutive patients with newly diagnosed Chagas disease and registered cardiac test results (ECG, ECHO, and CMR). We divided ECHO parameters into three tiers: 1) left ventricular ejection fraction, regional wall motion abnormality, and left ventricular diastolic dimension (ECHO-1); 2) other common ECHO parameters (ECHO-2); and 3) global longitudinal strain (GLS) (ECHO-3). Cardiac magnetic resonance included global and segmental biventricular function, the presence of myocardial fibrosis, and edema. The study comprised 100 patients from South America. The mean age was 43.9 ± 0.9 years, and 66% were women. Mean time living in Spain was 9.7 ± 0.5 years. The ECG revealed ≥ 2 abnormal findings in 47% of patients. ECHO-1 was abnormal in 22% of patients, ECHO-2 in 52%, and GLS in 16%. Cardiac magnetic resonance was abnormal in 50% of cases, and in 3% of these, ECHO was normal. When ECG and conventional ECHO were taken together, abnormalities were detected in 83% of patients. This value increased to 86% and 92% for GLS and CMR, respectively. These findings suggest that ECG and conventional ECHO should be used routinely as standard cardiac tests for newly diagnosed cases of Chagas disease. The value of advanced ECHO techniques and CMR is low.

Coronavirus disease 2019 (COVID-19) could predispose to both venous and arterial thromboembolism, in an exaggerated immune response to the virus, especially in severe patients. Even though aortic clots are a rare entity, the pro-coagulant nature of COVID-19 is associated with thrombosis in atypical locations and should be considered in patients with severe abnormalities in coagulation parameters. We describe a series of three cases of aortic thrombi diagnosed by computerized tomography (CT) angiography in patients with confirmed SARS-CoV-2 infection.

URGENCIAS MÉDICAS CLÍNICO QUIRÚRGICAS es un libro que se abraza al manto de la urgencia médica considerada como toda situación que, desde el punto de vista médico, plantea una amenaza para la salud o vida de una persona. Lo cual comprende todo aquel problema patológico que se presenta como nueva enfermedad o como descompensación de una patología crónica, lo cual implica que de retrasarse su diagnóstico y/o tratamiento, podría agravar o alargar la historia natural de la enfermedad, precisando asistencia de primera, segunda, o tercera prioridad según su envergadura. Por otro lado, se entiende de manera general como una urgencia quirúrgica, todo aquel proceso que sufre un paciente y que si no se opera con carácter urgente pone en peligro la vida de la persona enferma, lo cual requiere un diagnóstico preciso y rápido siendo crucial con el fin de evitar intervenciones quirúrgicas innecesarias y por el hecho de que, en ocasiones, la demora del tratamiento puede condicionar graves complicaciones e incluso ser mortal. En este sentido, al momento de hacer uso de texto se considera imprescindible tener presente una serie de consideraciones bajo las cuales se desplaza y despliega el mismo. La Organización Mundial de la Salud hace referencia a una urgencia cuando la problemática se debe resolver inmediatamente, lo cual implica una acción de resolución sin ningún tipo de demoras ante la dificultad presentada por la persona. En otras palabras, las urgencias médicas se refieren a una situación en donde se requiere asistencia médica en un lapso reducido de tiempo, pero este no implica riesgo en la vida de los que la involucra ni genera peligro en la evolución de su afección. Cuando se habla de urgencia se hace referencia a una evolución lenta y que no necesariamente es mortal para el afectado.

Background Corticosteroids are one of the few drugs that have shown a reduction in mortality in coronavirus disease 2019 (COVID-19). In the RECOVERY trial, the use of dexamethasone reduced 28-day mortality compared to standard care in hospitalized patients with suspected or confirmed COVID-19 requiring supplemental oxygen or invasive mechanical ventilation. Evidence has shown that 30% of COVID-19 patients with mild symptoms at presentation will progress to acute respiratory distress syndrome (ARDS), particularly patients in whom laboratory inflammatory biomarkers associated with COVID-19 disease progression are detected. We postulated that dexamethasone treatment in hospitalized patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease might lead to a decrease in the development of ARDS and thereby reduce death. Methods/design This is a multicenter, randomized, controlled, parallel, open-label trial testing dexamethasone in 252 adult patients with COVID-19 pneumonia who do not require supplementary oxygen on admission but are at risk factors for the development of ARDS. Risk for the development of ARDS is defined as levels of lactate dehydrogenase > 245 U/L, C-reactive protein > 100 mg/L, and lymphocyte count of 9/L. Eligible patients will be randomly assigned to receive either dexamethasone or standard of care. Patients in the dexamethasone group will receive a dose of 6 mg once daily during 7 days. The primary outcome is a composite of the development of moderate or more severe ARDS and all-cause mortality during the 30-day period following enrolment. Discussion If our hypothesis is correct, the results of this study will provide additional insights into the management and progression of this specific subpopulation of patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease. Trial registration ClinicalTrials.gov NCT04836780. Registered on 8 April 2021 as EARLY-DEX COVID-19.

Background & aims People who inject drugs (PWID) and other marginalized populations with high hepatitis C virus (HCV) infection rates represent a unique challenge for treatment initiation due to health, administrative and social barriers. We analyzed the HCV cascade of care (CoC) in some vulnerable subpopulations in Madrid, Spain, when using a mobile point of care. Methods From 2019 to 2021, a mobile unit was used to screen active HCV using a linkage-to-care and two-step point-of-care-based strategy. Viremic participants were grouped into four subgroups: PWID, homeless individuals and people with a mental health disorder (MHD) and alcohol use disorder (AUD). Logistic regression, and Cox and Aalen's additive models were used to analyze associated factors and differences between groups. Results A prospectively recruited cohort of 214 HCV infected individuals (73 PWID, 141 homeless, 57 with a MHD and 91 with AUD) participated in the study. The overall HCV CoC analysis found that: 178 (83.1%) attended a hospital, 164 (76.6%) initiated direct-acting antiviral therapy and 141 (65.8%) completed therapy, of which 99 (95.2%) achieved sustained virological response (SVR). PWID were significantly less likely to initiate treatment, while individuals with AUD waited longer before starting treatment. Both people with AUD and PWID were significantly less likely to complete HCV treatment. Conclusions Overall, SVR was achieved in the majority of the participants treated. However, PWID need better linkage to care and treatment, while PWID and AUD need more support for treatment completion.

Background An estimated 58 749 people with opioid use disorder engaged in opioid agonist therapy (OAT) in 1132 centers in Spain during 2017. We aimed to calculate the incidence of severe injection-related infections in people who inject drugs (PWID) engaged in OAT in harm reduction settings without a safe consumption space. Methods A retrospective cohort study was performed in PWID engaged in OAT and in a mobile harm reduction unit to quantify admissions to a referral hospital for any severe injection-related infections between 1 January 2016 and 31 December 2019. A Cox proportional hazard regression analysis was used to assess factors associated with any severe injection-related infection. Results Two hundred thirty-seven PWID who engaged in OAT were included in the study. After a median follow-up of 5.5 months (interquartile range [IQR], 1.3–22.7 months), a total of 104 episodes of severe injection-related infections occurred among 56 individuals, and admission due to a second event occurred in 35.7% of this same group. The incidence density of any type of severe injection-related infection was 26.8 (95% confidence interval [CI], 20.2–34.8) episodes per 100 person-years, and the incidence density of complicated skin and soft tissue infections that required hospital admission was 20.4 (95% CI, 15.0–27.3) episodes per 100 person-years. Fifty-six (53.8%) of all the episodes were patient-directed discharge (PDD), and people who had 2 or more hospital admissions had a higher PDD frequency. Conclusions Severe injection-related infections remain highly prevalent among PWID cared for in a harm reduction setting without a safe consumption space. PDD was more frequent among higher-risk individuals who presented 2 or more hospital readmissions., The incidence of severe injection-related infections and hospital readmissions among people who inject drugs attended was very high when harm reduction services did not provide safe consumption spaces. Patient-directed discharge was frequent in individuals who had 2 or more hospital readmissions.

Background In a recent study, autoantibodies neutralizing type I interferons (IFNs) were present in at least 10% of cases of critical COVID-19 pneumonia. These autoantibodies neutralized most type I IFNs but rarely IFN-beta. Objectives We aimed to define the prevalence of autoantibodies neutralizing type I IFN in a cohort of patients with severe COVID-19 pneumonia treated with IFN-beta-1b during hospitalization and to analyze their impact on various clinical variables and outcomes. Methods We analyzed stored serum/plasma samples and clinical data of COVID-19 patients treated subcutaneously with IFN-beta-1b from March to May 2020, at the Infanta Leonor University Hospital in Madrid, Spain. Results The cohort comprised 47 COVID-19 patients with severe pneumonia, 16 of whom (34%) had a critical progression requiring ICU admission. The median age was 71 years, with 28 men (58.6%). Type I IFN-alpha- and omega-neutralizing autoantibodies were found in 5 of 47 patients with severe pneumonia or critical disease (10.6%), while they were not found in any of the 118 asymptomatic controls (p = 0.0016). The autoantibodies did not neutralize IFN-beta. No demographic, comorbidity, or clinical differences were seen between individuals with or without autoantibodies. We found a significant correlation between the presence of neutralizing autoantibodies and higher C-reactive protein levels (p = 5.10e−03) and lower lymphocyte counts (p = 1.80e−02). No significant association with response to IFN-beta-1b therapy (p = 0.34) was found. Survival analysis suggested that neutralizing autoantibodies may increase the risk of death (4/5, 80% vs 12/42, 28.5%). Conclusion Autoantibodies neutralizing type I IFN underlie severe/critical COVID-19 stages in at least 10% of cases, correlate with increased C-RP and lower lymphocyte counts, and confer a trend towards increased risk of death. Subcutaneous IFN-beta treatment of hospitalized patients did not seem to improve clinical outcome. Studies of earlier, ambulatory IFN-beta treatment are warranted. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-021-01036-0.

Background and aims: An estimated 68,297 people with opioid use disorder engage in opioid agonist therapy (OAT) in Spain. We aimed to calculate the incidence of severe injection-related infections in people who inject drugs (PWID) engaged in OAT in a harm reduction setting without a safe injection site (SCS).Methods: A retrospective cohort study was performed in PWID engaged in OAT and in a mobile harm reduction unit to identify who was admitted to a referral hospital for any severe injection-related infections between 1 Jan 2016 and 31 Dec 2019. A Cox proportional hazard regression analysis was used to assess factors associated with any severe injection-related infection.Results: 237 PWID engaged in OAT were included. After a median follow-up of 5.5 months (IQR 1.3–22.7), a total of 104 episodes of severe injection-related infections occurred in 56 individuals, and admission for a second event occurred in 35.7% of this same group. The incidence density of any type of severe injection-related infection was 26.8 (20.2–34.8) episodes per 100 PY, and the incidence density of complicated skin and soft tissue infections (SSTIs) that required hospital admission was 20.4 (15.0–27.3) episodes per 100 PY. Fifty-six (53.8%) of all the episodes were patient-directed discharge (PDD), and people who had two or more hospital admissions had a higher PDD frequency.Conclusion: Severe injection-related infections remain highly prevalent among PWID cared for in a harm reduction setting without a SCS. PDD were more frequent in higher-risk individuals who presented two or more hospital readmissions.

Background: In a recent study, autoantibodies neutralizing type I interferons (IFNs) were present in at least 10% of cases of critical COVID-19 pneumonia. These autoantibodies neutralized most type I IFNs but rarely IFN-beta.Objectives: We aimed to define the prevalence of autoantibodies neutralizing type I IFN in a cohort of patients with severe COVID-19 pneumonia treated with IFN-beta-1b during hospitalization and to analyze their impact on various clinical variables and outcomes.Methods: We analyzed stored serum/plasma samples and clinical data of COVID-19 patients treated subcutaneously with IFN-beta-1b from March to May 2020, at the Infanta Leonor University Hospital in Madrid, Spain. Results: The cohort comprised 47 COVID-19 patients with severe pneumonia, 16 of whom (34%) had a critical progression requiring ICU admission. The median age was 71 years, with 28 men (58.6%). Type I IFN-alpha- and omega-neutralizing autoantibodies were found in 5 of 47 patients with severe pneumonia or critical disease (10.6%). The autoantibodies did not neutralize IFN-beta. No demographic, comorbidity, or clinical differences were seen between individuals with or without autoantibodies. We found a significant correlation between the presence of neutralizing autoantibodies and higher C-reactive protein levels (p=5.10e-03) and lower lymphocyte counts (p=1.80e-02). Survival analysis suggested that neutralizing autoantibodies may increase the risk of death (4/5, 80% vs 12/42, 28.5%).Conclusion: Autoantibodies neutralizing type I IFN underlie severe/critical COVID-19 stages in at least 10% of cases, correlate with increased C-RP and lower lymphocyte counts, and confer a trend towards increased risk of death. Subcutaneous IFN-beta treatment of hospitalized patients did not seem to improve clinical outcome. Studies of earlier, ambulatory IFN-beta treatment are warranted.

Background The burden of human immunodeficiency virus (HIV) infection in people who use drugs (PWUD) is significant. We aimed to screen HIV infection among PWUD and describe their retention in HIV care. Besides, we also screen for hepatitis C virus (HCV) infection among HIV-seropositive PWUD and describe their linkage to care. Methods We conducted a prospective study in 529 PWUD who visited the “Cañada Real Galiana” (Madrid, Spain). The study period was from June 1, 2017, to May 31, 2018. HIV diagnosis was performed with a rapid antibody screening test at the point-of-care (POC) and HCV diagnosis with immunoassay and PCR tests on dried blood spot (DBS) in a central laboratory. Positive PWUD were referred to the hospital. We used the Chi-square or Fisher’s exact tests, as appropriate, to compare rates between groups. Results Thirty-five (6.6%) participants were positive HIV antibodies, but 34 reported previous HIV diagnoses, and 27 (76%) had prior antiretroviral therapy. Among patients with a positive HIV antibody test, we also found a higher prevalence of homeless (P P P = 0.002). All participants received HIV test results at the POC. Of the 35 HIV positives, 28 (80%) were retained in HIV medical care at the end of the HIV screening study (2018), and only 22 (62.9%) at the end of 2020. Moreover, 12/35 (34.3%) were positive for the HCV RNA test. Of the latter, 10/12 (83.3%) were contacted to deliver the HCV results test (delivery time of 19 days), 5/12 (41.7%) had an appointment and were attended at the hospital and started HCV therapy, and only 4/12 (33.3%) cleared HCV. Conclusions We found almost no new HIV-infected PWUD, but their cascade of HIV care was low and remains a challenge in this population at risk. The high frequency of active hepatitis C in HIV-infected PWUD reflects the need for HCV screening and reinforcing the link to care.

COVID-19@Spain and COVID@HULP Study., [Objective] To develop and validate a prediction model of mortality in patients with COVID-19 attending hospital emergency rooms., [Design] Multivariable prognostic prediction model., [Setting] 127 Spanish hospitals., [Participants] Derivation (DC) and external validation (VC) cohorts were obtained from multicentre and single-centre databases, including 4035 and 2126 patients with confirmed COVID-19, respectively., [Interventions] Prognostic variables were identified using multivariable logistic regression., [Main outcome measures] 30-day mortality., [Results] Patients’ characteristics in the DC and VC were median age 70 and 61 years, male sex 61.0% and 47.9%, median time from onset of symptoms to admission 5 and 8 days, and 30-day mortality 26.6% and 15.5%, respectively. Age, low age-adjusted saturation of oxygen, neutrophil-to-lymphocyte ratio, estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, dyspnoea and sex were the strongest predictors of mortality. Calibration and discrimination were satisfactory with an area under the receiver operating characteristic curve with a 95% CI for prediction of 30-day mortality of 0.822 (0.806–0.837) in the DC and 0.845 (0.819–0.870) in the VC. A simplified score system ranging from 0 to 30 to predict 30-day mortality was also developed. The risk was considered to be low with 0–2 points (0%–2.1%), moderate with 3–5 (4.7%–6.3%), high with 6–8 (10.6%–19.5%) and very high with 9–30 (27.7%–100%)., [Conclusions] A simple prediction score, based on readily available clinical and laboratory data, provides a useful tool to predict 30-day mortality probability with a high degree of accuracy among hospitalised patients with COVID-19., This work was supported by Fundación SEIMC/GeSIDA. The funders had no role in study design, data collection, data interpretation or writing of the manuscript. JB, JRB, IJ, JC, JP and JRA received funding for research from Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, cofinanced by the European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014‐2020. Spanish AIDS Research Network (RIS) (RD16/0025/0017 (JB), RD16/0025/0018 (JRA), RD16CIII/0002/0006 (IJ)). Spanish Network for Research in Infectious Diseases (REIPI) (RD16/0016/0001 (JRB), RD16/0016/0005 (JC) and RD16/0016/0009 (JP)).

Background: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome-wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities. Methods: Peripheral blood samples were obtained from 407 confirmed COVID-19 patients 61 years of age and without comorbidities, 194 (47.7%) of whom had mild symptomatology that did not involve hospitalization and 213 (52.3%) had a severe clinical course that required respiratory support. The set of cases was divided into discovery (n = 207) and validation (n = 200) cohorts, balanced for age and sex of individuals. We analysed the DNA methylation status of 850,000 CpG sites in these patients. Findings: The DNA methylation status of 44 CpG sites was associated with the clinical severity of COVID-19. Of these loci, 23 (52.3%) were located in 20 annotated coding genes. These genes, such as the inflammasome component Absent in Melanoma 2 (AIM2) and the Major Histocompatibility Complex, class I C (HLA-C) candidates, were mainly involved in the response of interferon to viral infection. We used the EWAS-identified sites to establish a DNA methylation signature (EPICOVID) that is associated with the severity of the disease. Interpretation: We identified DNA methylation sites as epigenetic susceptibility loci for respiratory failure in COVID-19 patients. These candidate biomarkers, combined with other clinical, cellular and genetic factors, could be useful in the clinical stratification and management of patients infected with the SARS-CoV-2., The Unstoppable campaign of the Josep Carreras Leukaemia Foundation, the Cellex Foundation and the CERCA Programme/Generalitat de Catalunya.

BackgroundCOVID-19 clinical presentation ranges from asymptomatic to fatal outcome. This variability is due in part to host genome specific mutations. Recently, two families in which COVID-19 segregates like an X-linked recessive monogenic disorder environmentally conditioned by SARS-CoV-2 have been reported leading to identification of loss-of-function variants in TLR7.ObjectiveWe sought to determine whether the two families represent the tip of the iceberg of a subset of COVID-19 male patients.MethodsWe compared male subjects with extreme phenotype selected from the Italian GEN-COVID cohort of 1178 SARS-CoV-2-infected subjects (TLR7 as the most important susceptibility gene.ResultsRare TLR7 missense variants were predicted to impact on protein function in severely affected males and in none of the asymptomatic subjects. We then investigated a similar white European cohort in Spain, confirming the impact of TRL7 variants. A gene expression profile analysis in peripheral blood mononuclear cells after stimulation with TLR7 agonist demonstrated a reduction of mRNA level of TLR7, IRF7, ISG15, IFN-□ and IFN-γ in COVID-19 patients compared with unaffected controls demonstrating an impairment in type I and II INF responses.ConclusionYoung males with TLR7 loss-of-function mutations and severe COVID-19 in the two reported families represent only a fraction of a broader and complex host genome situation. Specifically, missense mutations in the X-linked recessive TLR7 disorder may significantly contribute to disease susceptibility in up to 4% of severe COVID-19.Clinical ImplicationIn this new yet complex scenario, our observations provide the basis for a personalized interferon-based therapy in patients with rare TLR7 variants.CAPSULE SUMMARYOur results in large cohorts from Italy and Spain showed that X-linked recessive TLR7 disorder may represent the cause of disease susceptibility to COVID-19 in up to 4% of severely affected young male cases.

The burden of hepatitis C virus (HCV) infection among people who use drugs (PWUDs) is considerable. We aimed to screen for HCV infection using the fingerstick dried blood spot (DBS) test and to describe the cascade of hepatitis C care among PWUDs in Madrid, Spain. We also evaluated the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) in this population.We carried out a prospective study and collected samples and epidemiological data using a mobile unit. Viral infections were tested by immunoassay and RT-PCR assay. PWUDs with a positive result were contacted and referred to a specialized health center to confirm and treat the HCV infection.We studied 529 PWUD samples; 49.7% were from persons who had previously used injection drugs (IDUs). Of these, 152 (28.7%) were positive for HCV antibodies, 122 (23.1%) for HCV RNA, 23 (4.3%) for HBsAg, and two (0.4%) for HDV antibodies (8.7% of those with hepatitis B). People who inject drugs (PWID) more frequently had positive HCV antibody titers (52% vs. 7.3%; p0.001) and a positive HCV RNA test result (40.2% vs. 7.3%; p0.001) than non-PWID. The time from sample collection to test results was 19 days. The next 104 individuals (85.2%) with active HCV infection were contacted to report their HCV test results. Of these, 63 (51.6%) had an appointment, 62 (50.8%) were evaluated in the hospital, and 56 (45.9%) started HCV therapy.HCV screening using fingerstick DBS was an excellent tool for determining HCV prevalence and other chronic hepatitis viruses (HBV and HDV) in PWUDs. However, linkage to care was limited, mainly with respect to the initiation of HCV therapy.

The high vulnerability of transgender (TG) persons to HIV infection and the difficulties associated with access to health services can lead to delays in the diagnosis and treatment of HIV infection, thus increasing the risk of transmission of HIV by this population. We performed a retrospective study to analyze the main characteristics of TG living with HIV infection in a hospital in Madrid, Spain and to identify issues related to lack of access to the health care system and combination antiretroviral therapy (cART). We analyzed 28 TG, of whom 22 (78.6%) were TG women. Median age was 28 years (interquartile range [IQR]: 29–45), 24 (85.7%) were Latin American (all of them without health insurance), and 12 (42.8%) were sex workers. Accessibility to the health system was more difficult for 22 (78.6%) of foreign-born TG people living with HIV, with a median delay to initiation of cART of six months (IQR: 2–24). These values were greater than those recorded for the control group comprising other people living with HIV (16.9% and one month, respectively). At the first access to health care in our hospital, CD4+ cell count and HIV viral load (VL) were worse in TG patients, with a median baseline CD4+ cell count below 350 cells/µl and a higher median HIV VL, both in naïve patients (28.6%) and in pre-treated patients whose therapy was interrupted owing to access-related issues (46.4%). These data show high vulnerability to HIV infection among TG and highlight that issues associated with access to health care can cause delays in the diagnosis and treatment of HIV infection. Based on our results, we think that the health care system should adapt to the sociodemographic, clinical, and behavioral characteristics of TG people living with HIV and develop specific, targeted preventive programs to address the vulnerability of this group.

Coronavirus disease 2019 (COVID-19) is suspected to predispose to both venous and arterial thromboembolism, in the context of an exaggerated immune response to the virus, especially in severe patients. Even though aortic thrombi are a rare entity, the new COVID-19 establishes the need to include them in the diagnosis, especially in patients with severe disease and no clinical improvement. Herein, we describe a series of three cases of aortic thrombi diagnosed by computerized tomography (CT) angiography in patients with confirmed SARS CoV-2 infection.

BACKGROUND AND AIMS: In comparison with men, women who use drugs (WWUD) have considerably more frequent and intense experiences with interpersonal violence, sexual abuse and trauma. The aim of this study was to identify issues related to gender-based vulnerability in a group of WWUD attended in a harm reduction facility in Madrid, Spain. MATERIAL AND METHODS: A cross-sectional study was conducted during a screening of blood borne infections. We included WWUD (smoked or injected heroin/cocaine) who were actively screened for HIV, HBV and HCV in a harm reduction setting in Madrid (Spain) from January to December 2017. WWUD were interviewed for gender-based abuse or violence using a face-to-face questionnaire by a trained interviewer. Aspects related to their social-epidemiological condition and gender-based vulnerability were collected. RESULTS: We included 109 women who were actively using drugs. The median age was 39 (IQR 35-47) years, 84.4% were Spanish born, 22.9% were homeless, 43 (41.7%) had ever used injected drugs, 29 (26.6%) were currently using injected drugs, and 27.1% had mental health disorders. Aspects related to gender-based vulnerability were collected. Among those surveyed, they reported having ever suffered emotional or psychological damage (88%), having experienced at least one incident of serious physical injury by a male partner (71%), and having ever suffered sexual abuse (49%). In addition, 28% had ever exchanged sex for money/drugs. When compared to women that did not use injecting drugs, those who injected drugs had more frequently exchanged sex for money/drugs (55% vs 21%, p = 0.003). CONCLUSIONS: A high proportion of WWUD suffer psychological or physical violence by partners denoting gender-based vulnerability. Interventions in harm reduction settings with a multidisciplinary and gender-based approach should be implemented. JV has received research grants and honoraria for lectures from Gilead Sciences and travel grants from Gilead Sciences, ViiV, Merck and Janssen; SM has been involved in speaking activities and has received grants for research from Abbott, Boehringer&Ingelheim, Bristol-Myers Squibb, Gilead, Glaxo Smith Kline, Janssen Cilag, Merck Sharp&Dohme, Pfizer, Roche, and Schering Plough.; JT has received honoraria for talks from Gilead and Merck; PR has received grant/research support from Merck, Gilead, Janssen, AbbVie and ViiV. Other authors declare that they have no conflicts of interest. Sí

The scenario of people living with HIV has dramatically changed, and nowadays older adults with HIV constitute almost half of the HIV population—and the percentage is growing. Frailty and geriatric syndromes have been highly demonstrated among older adults with HIV; therefore, the application of geriatric medicine principles to their approach has become essential. Geriatric-HIV Medicine, specific, collaborative work between HIV specialists and geriatricians, is a young discipline that has the goal of ensuring a global and specific approach to older patients that is focused on function and the continuum of care. The geriatrician’s role adds value to the care of older people living with HIV through Comprehensive Geriatric Assessment for those patients who can benefit but goes beyond the clinical approach and involves generating scientific evidence that impacts and changes the current model of care.

Clinicians sometimes use switching strategies based on regimens such as RAL + ABC/3TC or RPV + ABC/3TC in order to resolve tolerability or safety issues associated with conventional recommended first-line strategies. Despite the low genetic barrier of these regimens, high safety and efficacy rates have been reported in retrospective studies.

OBJECTIVES Current harm reduction strategies will probably remain insufficient to eliminate HIV transmission among drug users. We aimed to estimate the HIV seroconversion rate among drug users followed at a harm reduction unit (HRU) to evaluate the potential use of preexposure prophylaxis as a prevention tool. DESIGN AND METHODS A cohort of drug users has been followed at an HRU in Madrid between 2013 and 2016. Individuals who were HIV negative at baseline and who had at least one retest for HIV infection were eligible. Kaplan-Meier methods were employed to estimate the incidence density. RESULTS A total of 954 drug users had at least an HIV test. At baseline, 260 were HIV negative and had at least one follow-up HIV test. After 330.89 person-years of risk for HIV infection, 10 (3.8%) seroconverted. Overall incidence density of HIV seroconversion was 3.02 [95% confidence interval (CI); 1.4-5.5] per 100 person-years, with differences according to hepatitis C virus (HCV) serostatus: 1.17 (95% CI; 0.1-4.2) per 100 person-years in negative HCV individuals and 4.98 (95% CI; 2.1-9.8) per 100 person-years in positive HCV individuals. In the multivariable analysis, infection with HCV remained independently associated with time to HIV seroconversion (adjusted hazard ratio = 6.43; 95% CI; 1.1-36.5, P = 0.035). CONCLUSION Despite efforts in HIV prevention in a HRU, a high incidence of HIV was found among active drug users. Positive HCV status is a strong predictor of HIV seroconversion. In this context, preexposure prophylaxis implementation should be considered as an additional tool for HIV prevention in this population.

Chemsex is the use of psychoactive substances, mainly gamma-hydroxybutyrate, 4-methylmethcathinone (mephedrone), and methamphetamines to facilitate and enhance the experience of sexual intercourse. The toxicity of these drugs may be problematic and lead to a fatal outcome in some patients. We present the case of a 26-year-old man living with human immunodeficiency virus whose frequent use of mephedrone caused his death.