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Objectives Thromboinflammation, resulting from a complex interaction between thrombocytopathy, coagulopathy, and endotheliopathy, contributes to increased mortality in COVID-19 patients. MR-proADM, as a surrogate of adrenomedullin system disruption, leading to endothelial damage, has been reported as a promising biomarker for short-term prognosis. We evaluated the role of MR-proADM in the mid-term mortality in COVID-19 patients. Methods A prospective, observational study enrolling COVID-19 patients from August to October 2020. A blood sample for laboratory test analysis was drawn on arrival in the emergency department. The primary endpoint was 90-day mortality. The area under the curve (AUC) and Cox regression analyses were used to assess discriminatory ability and association with the endpoint. Results A total of 359 patients were enrolled, and the 90-day mortality rate was 8.9%. ROC AUC for MR-proADM predicting 90-day mortality was 0.832. An optimal cutoff of 0.80 nmol/L showed a sensitivity of 96.9% and a specificity of 58.4%, with a negative predictive value of 99.5%. Circulating MR-proADM levels (inverse transformed), after adjusting by a propensity score including eleven potential confounders, were an independent predictor of 90-day mortality (HR: 0.162 [95% CI: 0.043-0.480]) Conclusions Our data confirm that MR-proADM has a role in the mid-term prognosis of COVID-19 patients and might assist physicians with risk stratification.

Background Mid-Regional pro-Adrenomedullin (MR-proADM) is an inflammatory biomarker that improves the prognostic assessment of patients with sepsis, septic shock and organ failure. Previous studies of MR-proADM have primarily focussed on bacterial infections. A limited number of small and monocentric studies have examined MR-proADM as a prognostic factor in patients infected with SARS-CoV-2, however there is need for multicenter validation. An evaluation of its utility in predicting need for hospitalisation in viral infections was also performed. Methods An observational retrospective analysis of 1861 patients, with SARS-CoV-2 confirmed by RT-qPCR, from 10 hospitals across Europe was performed. Biomarkers, taken upon presentation to Emergency Departments (ED), clinical scores, patient demographics and outcomes were collected. Multiclass random forest classifier models were generated as well as calculation of area under the curve analysis. The primary endpoint was hospital admission with and without death. Results Patients suitable for safe discharge from Emergency Departments could be identified through an MR-proADM value of ≤ 1.02 nmol/L in combination with a CRP (C-Reactive Protein) of ≤ 20.2 mg/L and age ≤ 64, or in combination with a SOFA (Sequential Organ Failure Assessment) score 0.85 nmol/L, in combination with a SOFA score ≥ 2 and LDH > 720 U/L, or in combination with a CRP > 29.26 mg/L and age ≤ 64, when MR-proADM was > 1.02 nmol/L. Conclusions This international study suggests that for patients presenting to the ED with confirmed SARS-CoV-2 infection, MR-proADM in combination with age and CRP or with the patient’s SOFA score could identify patients at low risk where outpatient treatment may be safe.

The World Health Organization declared the global SARS-CoV-2 infection a pandemic on March 11, 2020. The objective of this paper is to present its impact in terms of physical and mental health 22 months later.We have reviewed results from published meta-analysis and systematic reviews, and some individual articles on specific aspects of special interest. National information on infection comes for the Red Nacional de Vigilancia Epidemiológica (RENAVE).Up to the end of October, more than 250 million infections and 5 million deaths had been reported globally. In Spain, 4.7 million infections have been documented although the real figure might be above 7 million. The pandemic has reduced life expectancy, and its effects have been especially dramatic in people with comorbidities and the elderly. There is a worsening of mental health in the general population. It is foreseeable that some groups, such as health professionals, mostly women, and front-line workers, may have a greater risk of developing mental health pathologies. The pandemic and the control measures have had other undesirable consequences such as a decrease in healthcare utilization, an increase in sedentary lifestyle or an increase in gender violence. In addition to its immediate effect on morbidity and mortality, the control measures have damaged the overall health status of the global population.Longitudinal studies are necessary to determine the mid and long consequences of the pandemic and the control measures, and to identify and evaluate effective health interventions.

A randomized, double-blind, placebo-controlled study was conducted with the primary objective of assessing the effect of a natural extract of Sclerocarya birrea on glucose metabolism in subjects with prediabetes. The duration of the study was 90 days. Thirty-three subjects assigned to the experimental group (daily ingestion of 100 mg of the nutraceutical product) and 34 assigned to the placebo group completed the study. There were 36 men and 31 women with a mean age of 32.3 ± 14.1 years. In the area under the curve (AUC) of the oral glucose tolerance test (OGTT), statistically significant decreases in the experimental group at 40 and 90 days as compared with baseline were found, whereas significant changes in the placebo group were not observed. Within-group differences were statistically significant in favor of the experimental group for glucose peak at OGTT, serum insulin, insulin resistance markers, and flow-mediated dilation. Changes in lipid and anthropometric parameters were not observed, although there was a trend for lower cholesterol levels and a decrease in body weight in the experimental group. Decreases in systolic blood pressure were also higher among subjects in the experimental group. This exploratory study confirms the antidiabetic activity of Sclerocarya birrea in prediabetes. Further studies using better measurements of beta-cell function are needed to clarify the underlying mechanisms of the hypoglycemic effect of this natural compound.

Previous work established non-inferiority of switching participants who were virologically suppressed from daily oral standard of care to monthly long-acting intramuscular injections of cabotegravir plus rilpivirine over 96 weeks following a cabotegravir plus rilpivirine oral lead-in. Here, we report an evaluation of switching participants from standard of care oral regimens to long-acting cabotegravir plus rilpivirine via direct-to-injection or oral lead-in pathways.This study reports the week 124 results of the FLAIR study, an ongoing phase 3, randomised, open-label, multicentre (11 countries) trial. Antiretroviral therapy (ART)-naive participants who were virologically suppressed (HIV-1 RNA50 copies per mL) during the 20-week induction phase with standard of care were randomly assigned (1:1) to continue the standard of care oral regimen or switch to long-acting cabotegravir plus rilpivirine (283 per group) in the 100-week maintenance phase. Randomisation was stratified by sex at birth and baseline (pre-induction) HIV-1 RNA (100 000 or ≥100 000 copies per mL). Participants randomly assigned to long-acting therapy at baseline received a cabotegravir (30 mg) plus rilpivirine (25 mg) once daily oral lead-in for at least 4 weeks before first injection and could choose to continue long-acting cabotegravir (400 mg) plus rilpivirine (600 mg) every 4 weeks from week 100 or withdraw. At week 100, participants in the oral comparator ART group, in discussion with the investigator, could elect to switch to long-acting therapy (extension switch population), either direct-to-injection or with a 4 week oral lead-in (oral lead-in group), or withdraw. Week 124 endpoints included plasma HIV-1 RNA 50 or more copies per mL and less than 50 copies per mL (US Food and Drug Administration [FDA] Snapshot), confirmed virological failure (two consecutive HIV-1 RNA ≥200 copies per mL), and safety and tolerability. The study is registered at ClinicalTrials.gov, NCT02938520.Screening occurred between Oct 27, 2016, and March 24, 2017. At week 100, 232 (92%) of 253 participants transitioned to long-acting cabotegravir plus rilpivirine in the extension phase (111 [48%] in the direct-to-injection group and 121 [52%] in the oral lead-in group; extension switch population). 243 (86%) of the 283 who were randomly assigned to the long-acting therapy group continued the long-acting regimen into the extension phase. One (1%) participant in each extension switch group had 50 or more HIV-1 RNA copies per mL; 110 (99%) participants in the direct-to-injection group and 113 (93%) participants in the oral lead-in group remained suppressed (HIV-1 RNA50 copies per mL) at the week 124 Snapshot. The lower suppression rates in the oral lead-in group were driven by non-virological reasons. For participants in the randomly assigned long-acting group, 227 (80%) of 283 participants remained suppressed; at the week 124 Snapshot, 14 (5%) participants had HIV-1 RNA 50 or more copies per mL, including five additional participants since the week 96 analysis. The remaining 42 (15%) participants in the randomly assigned long-acting group had no virological data. Adverse events leading to withdrawal were infrequent, occurring in three (1%) participants in the extension switch population (one in the direct-to-injection group and two in the oral lead-in group) after 24 weeks of cabotegravir plus rilpivirine therapy, and 15 (5%) participants in the randomly assigned long-acting group up to 124 weeks of therapy. No deaths occurred in the extension phase. Overall, cabotegravir plus rilpivirine adverse event type, severity, and frequency were similar across all groups. Injection site reactions were the most common adverse event, occurring after 914 (21%) of 4442 injections in the extension switch population and 3732 (21%) of 17 392 injections in the randomly assigned long-acting group. Injection site reactions were mostly classified as mild-to-moderate in severity and decreased in incidence over time. Four (2%) of 232 participants in the extension switch population and seven (2%) of 283 in the randomly assigned long-acting group withdrew due to injection-related reasons.After 24 weeks of follow-up, switching to long-acting treatment with or without an oral lead-in phase had similar safety, tolerability, and efficacy, supporting future evaluation of the simpler direct-to-injection approach. The week 124 results for participants randomly assigned originally to the long-acting therapy show long-acting cabotegravir plus rilpivirine remains a durable maintenance therapy with a favourable safety profile.ViiV Healthcare and Janssen ResearchDevelopment.

© 2020 The Author(s)., [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 situation., IJ has received honoraria for participating in an advisory board from Gilead Sciences, and for educational activities from ViiV. JB has received research grants from AbbVie, Gilead Sciences, Merck, and ViiV, and honoraria for being a speaker or advisory board participation from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV. JRA received fees for participating in an advisory board, being a speaker, and research grant support from Viiv, Janssen, Gilead, MSD, Teva, Alexa and Serono. PR is involved as speaker or advisory board participant for Gilead Sciences, AbbVie and ViiV. JR-B, JP, JC and MY have no conflicts of interest to declare. SAM-COVID was funded by Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (COV20/01031) co-funded by European Union (ERDF/ESF, “Investing in your future”) and Fundación SEIMC/GeSIDA. In addition, Juan Berenguer, Jesús Rodríguez-Baño, Inmaculada Jarrín, Jordi Carratalá, Jerónimo Pachón, and José R Arribas 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 – co- financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020 through the networks: Spanish AIDS Research Network (RIS) [RD16/0025/0017 (JB), RD16/0025/0018 (JRA), RD16/0025/00XX (IJ)] and Spanish Network for Research in Infectious Diseases (REIPI)[RD16/0016/0001 (JRB), RD16/0016/0005 (JC), and RD16/0016/0009 (JP).

There is a need for more convenient, less frequent treatment to help address challenges associated with daily oral HIV treatment in people living with HIV, including stigma, pill burden, drug-food interactions, and adherence. The phase 3 ATLAS and FLAIR studies showed non-inferiority of long-acting cabotegravir and rilpivirine dosed every 4 weeks compared with standard oral therapy for the maintenance of virological suppression in adults with HIV-1 over 48 weeks. We present the 96-week findings.FLAIR is a randomised, phase 3, open-label, multicentre study done in 11 countries investigating whether switching to long-acting cabotegravir and rilpivirine is non-inferior to daily dolutegravir, abacavir, and lamivudine in virologically suppressed adults living with HIV-1. Antiretroviral therapy (ART)-naive participants received induction therapy with daily oral dolutegravir (50 mg), abacavir (600 mg), and lamivudine (300 mg) for 20 weeks. After 16 weeks, participants with less than 50 HIV-1 RNA copies per mL were randomly assigned (1:1) to continue the standard of care regimen (standard care group) or switch to receive daily oral cabotegravir 30 mg and rilpivirine 25 mg for at least 4 weeks followed by long-acting cabotegravir 400 mg and rilpivirine 600 mg, administered as two 2 mL intramuscular injections, every 4 weeks for at least 96 weeks (long-acting group). Randomisation was stratified by baseline (preinduction) HIV-1 RNA (100 000 or ≥100 000 copies per mL) and sex at birth and used GlaxoSmithKline-verified randomisation software (RandAll NG, version 1.3.3) for treatment assignment. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of 50 copies per mL or more assessed as per the US Food and Drug Administration (FDA) Snapshot algorithm at week 48, which has been reported previously. Here, we report the proportion of participants with 50 or more HIV-1 RNA copies per mL using the FDA Snapshot algorithm at week 96 (intention-to-treat population; non-inferiority margin 6%). The trial is registered with ClinicalTrials.gov, NCT02938520.Between Oct 27, 2016, and March 24, 2017, 809 participants were screened. 631 (78%) participants entered the induction phase and 566 (70%) were randomly assigned to either the standard care group (283 [50%] participants) or the long-acting group (283 [50%]). Median age was 34 years (IQR 29 to 43), 62 (11%) were 50 years or older, 127 (22%) were women (sex at birth), and 419 (74%) were white. At week 96, nine (3%) participants in each arm had 50 or more HIV-1 RNA copies per mL, with an adjusted difference of 0·0 (95% CI -2·9 to 2·9), consistent with non-inferiority established at week 48. Across both treatment groups, adverse events leading to withdrawal were infrequent (14 [5%] participants in the long-acting group and four [1%] in the standard care group). Injection site reactions were the most common adverse event, reported by 245 (88%) participants in the long-acting group; their frequency decreased over time. Median injection site reaction duration was 3 days (IQR 2 to 4), and 3082 (99%) of 3100 reactions were grade 1 or 2. No deaths occurred during the maintenance phase.The 96-week results reaffirm the 48-week results, showing long-acting cabotegravir and rilpivirine continued to be non-inferior compared with continuing a standard care regimen in adults with HIV-1 for the maintenance of viral suppression. These results support the durability of long-acting cabotegravir and rilpivirine, over an almost 2-year-long period, as a therapeutic option for virally suppressed adults with HIV-1.ViiV Healthcare and Janssen Research and Development.

A single-center, randomized, double-blind controlled trial was conducted to assess the efficacy of a food supplement based on a combination of grapefruit, bitter orange, and olive extracts administered for eight weeks (n = 51) versus placebo (n = 45) on reduction of cardiovascular risk in healthy volunteers. Study variables included flow-mediated vasodilation (FMD), blood pressure (BP), lipid profile, thrombotic status, oxidative stress biomarkers, inflammation-related biomarkers, anthropometric variables, quality of life, and physical activity. The per-protocol data set was analyzed. In the active product group, there were statistically significant within-group differences at eight weeks as compared with baseline in FMD, systolic and diastolic BP, total cholesterol, LDL-C, LDL-oxidase, oxidized/reduced glutathione ratio, protein carbonyl, and IL-6. Significant between-group differences in these variables were also found. Significant changes in anthropometric variables and quality of life were not observed in the study groups. Changes in the level of physical activity were not recorded. Treatment with the active product was well tolerated. All these findings, taken together, support a beneficial effect of supplementation with a mixture of grapefruit, bitter orange fruits, and olive leaf extracts on underlying mechanisms that may interact each other to decrease the cardiovascular risk in healthy people.

Midregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP) and sepsis. In this paper, we examined the ability of MR-proADM to predict organ damage and long-term mortality in sepsis patients, compared to that of procalcitonin, C-reactive protein and lactate.This was a prospective observational cohort, enrolling severe sepsis or septic shock patients admitted to internal service department. The association between biomarkers and 90-day mortality was assessed by Cox regression analysis and Kaplan-Meier curves. The accuracy of biomarkers for mortality was determined by area under the receiver operating characteristic curve (AUROC) analysis.A total of 148 patients with severe sepsis, according to the criteria of the campaign to survive sepsis, were enrolled. Eighty-five (57.4%) had sepsis according to the new criteria of Sepsis-3. MR-proADM showed the best AUROC to predict sepsis as defined by the Sepsis-3 criteria (AUROC of 0.771, 95% CI 0.692-0.850, p0.001) and was the only marker independently associated with Sepsis-3 criteria (OR = 4.78, 95% CI 2.25-10.14; p 0.001) in multivariate analysis. MR-proADM was the biomarker with the best AUROC to predict mortality in 90 days (AUROC of 0.731, CI 95% 0.612-0.850, p0.001) and was the only marker that kept its independence [hazard ratio (HR) of 1.4, 95% CI 1.2-1.64, p0.001] in multivariate analysis. The cut-off point of MR-proADM of 1.8 nmol/L (HR of 4.65, 95% CI 6.79-10.1, p0.001) was the one that had greater discriminative capacity to predict 90 days mortality. All patients with MR-proADM concentrations ≤0.60 nmol/L survived up to 90 days. In patients with SOFA ≤ 6, the addition of MR-proADM to SOFA score increased the ability of SOFA to identify non-survivors, AUROC of 0.65 (CI 95% 0.537-0.764) and AUROC of 0.700 (CI 95% 0.594-0.800), respectively (p 0.05 for both).MR-proADM is a good biomarker in the early identification of high risk septic patients and may contribute to improve the predictive capacity of SOFA scale, especially when scores are low.

El tratamiento con estatinas puede inducir toxicidad muscular con relativa frecuencia. Con una menor incidencia, también puede provocar una miopatía necrotizante autoinmune o una dermatomiositis, miopatías potencialmente graves con una presentación clínica, analítica e histológica características. El diagnóstico diferencial entre ambas patologías no siembre es fácil. Se expone el caso de una mujer de edad media que, tras iniciar tratamiento con atorvastatina, presenta un cuadro inequívoco de miopatía inflamatoria, pero difícil de encuadrar en un subtipo, con lesiones cutáneas a favor de dermatomiositis, sin embargo, histológicamente compatible con una miopatía necrotizante por estatinas.

Resumen Introduccion El objetivo de este estudio fue investigar el valor del fragmento N-terminal del propeptido natriuretico cerebral (NT-proBNP), proteina C reactiva (PCR) y procalcitonina (PCT) para predecir la mortalidad en pacientes septicos durante la hospitalizacion con un riesgo de mortalidad Sepsis-related Organ Failure Assessment (SOFA). Material y metodos Estudio observacional prospectivo realizado en pacientes hospitalizados con sepsis y riesgo SOFA Resultados Se analizaron un total de 174 pacientes. Diecisiete (9,8%) pacientes murieron durante la hospitalizacion. El ABC de NT-proBNP fue 0,793 (IC 95% 0,686-0,9; p 1.330 pg/ml (OR = 23,23; IC 95% 2,92-182,25; p = 0,003) y tener factores predisponentes para presentar sepsis (OR = 3,05; IC 95% 1,3-9,3; p = 0,044). Conclusiones En pacientes con bajo riesgo de mortalidad segun la puntuacion SOFA, los niveles de NT-proBNP obtenidos en las primeras 72 h despues del ingreso son un poderoso predictor de mortalidad. Su implementacion en la practica clinica podria mejorar la capacidad predictiva de la puntuacion de gravedad clinica en estos pacientes.

To assess the prognostic value of procalcitonin (PTC), C-reactive protein (CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and mid-regional pro-adrenomedullin (MR-proADM) in patients with influenza syndrome.Prospective study in patients admitted from the emergency department with influenza syndrome. Biomarker concentrations were measured in the first 24 h after admission and a test for influenza. The results were analyzed for ability to predict a hospital stay longer than 7 days, intensive care unit admission, or in-hospital death.Ninety-eight patients were included; the prognosis of 44 (44.9%) was classified as poor. The areas under the receiving operator characteristic curve were 0.68 (95% CI, 0.56-0.80) for NT-proBNP, 0.73 (95% CI, 0.62-0.84) for MR-proADM, and nonsignificant for PCT and CRP. The following variables were independently associated with a poor prognosis: pneumonia (OR, 7.46 [95% CI, 2.08-26.73]; P=.002), heart failure (OR, 5.16 [95% CI, 1.35-19.74]; P=.016), and NT-proBNP580 pg/mL (OR, 4.68 [95% CI, 1.53-14.26]; P=.006). In the 53 patients with confirmed A(H1N1) influenza, only NT-proBNP was an independent predictor of prognosis (adjusted OR, 5.75 [95% CI, 1.46- 22.61]; P=.012).NT-proBNP and MR-proADM were the only biomarkers with prognostic value. Only NT-proBNP was a useful predictor in patients with confirmed influenza.Analizar el valor pronóstico de la procalcitonina (PCT), la proteína C reactiva (PCR), el NT-proBNP y la región medial de la proadrenomedulina (MR-proADM) en pacientes hospitalizados con síndrome gripal.Estudio prospectivo realizado en pacientes hospitalizados desde urgencias por síndrome gripal. Se analizaron las concentraciones de biomarcadores en las primeras 24 h de ingreso y el test de gripe y se analizó su capacidad predictiva de mal pronóstico: estancia superior a 7 días, ingreso en unidad de cuidados intensivos o fallecimiento intrahospitalario.Se incluyeron 98 pacientes, 44 (44,9%) de ellos con mal pronóstico. Las áreas bajo la curva COR para mal pronóstico fueron de 0,68 (IC 95% 0,56-0,80) para NT-proBNP y de 0,73 (IC 95% 0,62-0,84) para la MRproADM, y no significativas para PCT y PCR. Las variables asociadas independientemente con mal pronóstico fueron: neumonía (OR 7,46 [IC 95% 2,08-26,73]; p = 0,002), insuficiencia cardiaca (OR 5,16 [IC 95% 1,35-19,74]; p = 0,016) y NT-proBNP580 pg/ml (OR 4,68 [IC 95% 1,53-14,26]; p = 0,006). En los 53 pacientes con gripe A(H1N1) confirmada, solo el NT-proBNP tuvo un valor pronóstico independiente (OR ajustado 5,75 [IC 95% 1,46-22,61]; p = 0,012).En pacientes con síndrome gripal, el NT-proBNP y la MR-proADM fueron los únicos biomarcadores con valor pronóstico, y solo el primero de ellos mantuvo esta asociación en pacientes con gripe confirmada.

Objectives Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV-infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UDP-glucuronosyl-transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line antiretroviral therapy (ART). Methods A multicentre, prospective cohort study of HIV-infected patients who started first-line ART with either ATV/r or EFV was conducted. Lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders. Results After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp-PLA2 [estimated difference -16.3; 95% confidence interval (CI) -31.4, -1.25; P = 0.03] and a significantly smaller increase in OxLDL (estimated difference -21.8; 95% CI -38.0, -5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI -14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated. Conclusions When compared with EFV, ATV/r-based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels.

The objective of this study was to investigate the long-term impact of low-level viremia (LLV) on all-cause mortality, AIDS and non-AIDS events (NAEs), and virological failure in patients receiving antiretroviral therapy (ART).We analyzed ART-naive adults from the cohort of the Spanish AIDS Research Network (CoRIS) who initiated ART from 2004 to 2015 and achieved plasma viral load (VL) below 50 copies per milliliter. LLV50-199 was defined as 2 consecutive VL between 50 and 199 copies per milliliter, and LLV200-499 as 2 consecutive VL between 50 and 499 copies per milliliter with at least one between 200 and 499 copies per milliliter. Multivariable Cox models were used to estimate the association of LLV with AIDS events/death, non-AIDS events, and virological failure.Of 5986 patients included, 237 (4.0%) experienced LLV50-199 and 168 (2.8%) developed LLV200-499. One hundred seventy-one patients died or developed an AIDS event, 245 had any serious NAE and 280 had virological failure. LLV200-499 was strongly associated with a higher risk of both AIDS events/death [adjusted hazard ratio (aHR), 2.89; 95% confidence interval (CI), 1.41 to 5.92] and virological failure (aHR, 3.25; 95% CI: 1.77 to 5.99), whereas no differences were observed between LLV50-199 and no LLV neither for AIDS events/death (aHR, 1.84; 95% CI: 0.89 to 3.82) nor virological failure (aHR, 1.42; 95% CI: 0.78 to 2.58). LLV was not associated with the occurrence of any serious NAE.In this cohort, LLV200-499 was strongly associated with AIDS events/death and virological failure, but not with any serious NAE. Therefore, vigorous treatment should be implemented in patients with more than 200 copies per milliliter.

To develop a nomograph to predict a poor outcome (death during hospitalization or a hospital stay longer than 15 days) in emergency patients with sepsis and at low risk of organ damage according to Sepsis-related Organ Failure Assessment (SOFA).Prospective, observational study carried out in a single universitary hospital. All patients admitted from the emergency department with sepsis and SOFA scores of 6 or lower were enrolled. We used bivariate logistic regression analysis to develop a predictive nomogram.A total of 174 patients were included. Seventeen patients (9.8%) died during hospitalization and the average hospital stay was greater than 15 days in 29 (16.7%) patient. The outcome was poor in a total of 42 patients (24.1%);. Independent variables that were significantly associated with a poor outcome were SOFA score (odds ratio [OR], 1.3; 95% CI, 1.06-1.71; P.05), C-reactive protein (CRP) concentration (OR, 1.04; 95% CI, 1.0-1.09; P.05), N-terminal fragment of brain natriuretic peptide (NT-proBNP) concentration over 1330 ng/mL (OR, 2.64; 95% CI, 1.17-6.22; P.05), and septic shock (OR, 8.3; 95% CI, 1.16-166.5; P.05). For a SOFA score of 2 or more the crude OR was 4.44 (95%, CI, 1.91-10.34) and the OR adjusted for other variables was 3.08 (95% CI, 1.24-7.69).A high percentage of patients predicted to be at low risk of organ failure had poor outcomes, associated with SOFA score, the presence of septic shock, CRP concentration, and elevated NT-proBNP concentration. The SOFA score by itself is an inadequate prognostic tool in patients at low risk of organ damage. Other clinical and analytical variables are required to complement the SOFA score.Elaborar un nomograma que permita predecir el mal pronóstico (mortalidad durante el ingreso o estancia media15 días) en pacientes procedentes de urgencias con sepsis y baja probabilidad de daño orgánico evaluado por SOFA (Sepsis-related Organ Failure Assessment).Estudio observacional prospectivo realizado en un único hospital. Se incluyeron de forma consecutiva pacientes del servicio de urgencias con sepsis y SOFA igual o inferior a 6 puntos. Se realizó un análisis de regresión logística binaria y se elaboró un nomograma predictivo.Se incluyeron 174 pacientes. Diecisiete (9,8%) pacientes fallecieron durante la hospitalización y 29 (16,7%) tuvieron una estancia media prolongada. En total, 42 (24,1%) pacientes tuvieron mal pronóstico. Las variables independientes de mal pronóstico fueron: la puntuación SOFA (OR 1,3; IC 95% 1,06-1,71; p0,05), las concentraciones de proteína C reactiva (PCR) (OR 1,04; IC 95% 1-1,09; p0,05), NT-proBNP1.330 ng/ml (OR 2,64; IC 95% 1,17-6,22; p0,05) y la presencia de shock séptico (OR 8,3; IC 95% 1,16-166,5; p0,05). Si tenemos en cuenta el índice SOFA= 2, la OR cruda fue 4,44 (IC 95% 1,91-10,34) y ajustada por el resto de variables fue de 3,08 (IC 95%, 1,24-7,69).Una elevada proporción de pacientes con baja probabilidad de tener daño orgánico tuvieron mal pronóstico en relación con la puntuación en la escala SOFA, la presencia de shock séptico, concentraciones de PCR y NTproBNP. La utilización de la escala pronóstica SOFA en pacientes con bajo riesgo es insuficiente para predecir el pronóstico en estos pacientes y se hace necesario complementarla con otras variables clínicas y analíticas.

Dalbavancin is a lipoglycopeptide with a very prolonged half-life enabling treatment with a single intravenous administration that has been approved to treat complicated skin and soft-tissue infections. Information on the efficacy and safety of dalbavancin in other situations is very scarce. This retrospective study included adult patients who received at least one dose of dalbavancin between 2016 and 2017 in 29 institutions in Spain. The primary objective was to report the use of dalbavancin in clinical practice, including its efficacy and tolerability. The potential impact of dalbavancin on reducing the length of hospital stay and hospital costs was also evaluated. A total of 69 patients received dalbavancin during the study period (58.0% male; median age 63.5 years). Dalbavancin was used to treat prosthetic joint infection (29.0%), acute bacterial skin and skin-structure infection (21.7%), osteomyelitis (17.4%) and catheter-related bacteraemia (11.6%). These infections were mainly caused by Staphylococcus aureus (27 isolates), coagulase-negative staphylococci (24 isolates) and Enterococcus spp. (11 isolates). All but two patients received previous antibiotics for a median of 18 days. Dalbavancin was administered for a median of 21 days (range 7-168 days), and concomitant antimicrobial therapy was prescribed to 25 patients (36.2%). The overall clinical success rate of dalbavancin was 84.1%. Adverse events, mainly mild in intensity, were reported in nine patients. Overall, dalbavancin was estimated to reduce hospitalisation by 1160 days, with an estimated overall cost reduction of €211 481 (€3064 per patient). Dalbavancin appears to be an effective therapy for many serious Gram-positive infections.

Novel strategies are necessary to decrease inflammatory parameters in successfully treated HIV-infected patients. Our aim was to evaluate the maintenance of viral suppression and potential changes in inflammatory, immune-activation and coagulation biomarkers in virologically suppressed HIV-infected patients switched to a nucleoside reverse transcriptase inhibitor-sparing (NRTI) and maraviroc (MVC)-containing combined antiretroviral therapy (cART). Fifty-eight HIV-infected patients were observed after their treatment regimens were changed to MVC 150mg/once daily plus ritonavir-boosted protease inhibitor therapy. Activation-, inflammation- and coagulation-associated biomarkers and mitochondrial (mt)DNA were analyzed after a median of 24weeks of follow-up. We observed that after changing to an NRTI-sparing regimen, 96.6% of HIV-patients on viral suppressive cART maintained viral suppression and their CD4+ T cell counts did not change significantly (median of 31weeks of follow-up). This cART switch reduced soluble CD40 ligand (p=0.002), beta-2 microglobulin (p=0.025), and soluble CD14 (p=0.009) in patients with higher baseline levels of these inflammation biomarkers after a median of 24weeks of follow-up. The results of our study show that changing to NRTI-sparing dual therapy decreased the levels of inflammatory biomarkers and maintained the immune-virologic efficacy. The potential benefits of this regimen warrant further investigation to uncover the association of this therapy with the potential decrease in the morbidity and mortality of HIV-infected patients from non-AIDS-defining illnesses.

The purpose of this study was to investigate the value of N-terminal pro brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and procalcitonin (PCT) in predicting mortality in septic patients during hospitalization with mortality risk10% evaluated by Sepsis-related Organ Failure Assessment (SOFA).Prospective, observational study performed in sepsis patients with SOFA risk10%. We obtained levels of biomarkers in the first 72h after admission in hospital. All patients were monitored during hospitalization or until death. We used ROC curves to determine area under curve (AUC) and identify the best cutoff concentrations to predict mortality.A total of 174 patients were analyzed. Seventeen (9.8%) patients died during hospitalization. The AUC of NT-proBNP was 0.793 (95% CI 0.686-0.9; P.0005) compared to AUC of CRP (0.728; 95% CI 0.617-0.839; P=.004) and AUC of PCT (0.684; 95% CI 0.557-0.811; P=.019). Factors independently associated with in-hospital mortality were NT-proBNP1,330pg/ml (OR=23.23; 95% CI 2.92-182.25; P=.003) and to have predisposing factors (OR=3.05; 95% CI 1.3-9.3; P=.044) CONCLUSIONS: In patients with low mortality risk according to SOFA score, NT-proBNP obtained in the first 72h after admission prove to be a powerful predictor of mortality. Their implementations in clinical practice would improve the predictive ability of clinical severity scores.

A proportion of HIV-patients does not normally restore their CD4 counts despite virological response to HAART. Those whose CD4 counts persistently remain closed to the critical threshold for opportunistic infections deserve special interest. To study the risk factors, the long-term CD4 counts evolution, and the risk of death of patients who persistently maintain low CD4 counts, despite virological response to HAART, within a multicenter, hospital-based cohort study. A total of 147 patients were selected from CoRIS-MD and classified into a "Low-Group" or a "High-Group", depending on their CD4 counts after two-years of effective HAART (threshold 250 cells/microL). Associated risk factors were analysed by logistic regression, the CD4 dynamics were evaluated over a total period of 7.70 years (IQR, 6.70-9.00), and mortality was estimated by Cox proportional hazard. A total of 40 patients (27%) were classified into the "Low-Group". The odds ratio for this group increased with age, being 4.56 (2.23-9.33) for over 40, and was also higher among IDU, 3.63 (1.04-12.68). Six years thereafter, among these patients, only a 30% exceeded 350 CD4 cells/microL and a 12% exceeded 500 CD4 cells/microL. Furthermore, the "Low-Group" had a death rate of 2.42 per 100 persons/year (95%CI, 1.01-5.81), although once adjusted by age the estimates were no longer significant [4.14 (0.87-19.72)]. Our results suggest that those HIV patients who have not overcome the critical threshold of 250 CD4 cells/microL after a two years period of virologically effective HAART do persist with the aforementioned failure of CD4 restoration for a much longer time.

Cuando todavia estamos digiriendo la «multirresistencia» (insulina y leptina, y probablemente la resistina) del paciente con sindrome X metabolico, el mas prevalente (el 25% de la poblacion) y de mayor riesgo cardiovascular, nos llega una nueva resistencia, la «resistencia a la aspirina». Sospechada hace mas de 50 anos, hoy disponemos de informacion suficiente para analizar sus causas y consecuencias, asi como la problematica relacionada con su tratamiento, lo que le confiere una entidad plenamente establecida, y que consideramos merecedora de un apartado especifico en el estudio de la enfermedad cardiovascular

Current clinical guidelines consider regimens consisting of either ritonavir-boosted atazanavir or ritonavir-boosted lopinavir and a nucleoside reverse transcriptase inhibitor (NRTI) backbone among their recommended and alternative first-line antiretroviral regimens. However, these guidelines are based on limited evidence from randomized clinical trials and clinical experience.We compared these regimens with respect to clinical, immunologic, and virologic outcomes using data from prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States in the HIV-CAUSAL Collaboration, 2004-2013. Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started a lopinavir or an atazanavir regimen. We estimated the 'intention-to-treat' effect for atazanavir vs lopinavir regimens on each of the outcomes.A total of 6668 individuals started a lopinavir regimen (213 deaths, 457 AIDS-defining illnesses or deaths), and 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths). The adjusted intention-to-treat hazard ratios for atazanavir vs lopinavir regimens were 0.70 (95% confidence interval [CI], .53-.91) for death, 0.67 (95% CI, .55-.82) for AIDS-defining illness or death, and 0.91 (95% CI, .84-.99) for virologic failure at 12 months. The mean 12-month increase in CD4 count was 8.15 (95% CI, -.13 to 16.43) cells/?L higher in the atazanavir group. Estimates differed by NRTI backbone.Our estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a greater 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for atazanavir compared with lopinavir regimens.? The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The aim was to analyze clinical complications in HIV-infected subjects who persistently maintain low CD4 levels despite virological response to cART in the Spanish CoRIS cohort. The main inclusion criteria were CD4 counts

La toxicidad pulmonar por amiodarona es un efecto secundario infrecuente pero que puede ser fatal en los pacientes tratados con este farmaco. En la actualidad, el principal problema es que no disponemos de la herramienta necesaria para predecir o detectar que pacientes la van a desarrollar. El KL-6 serico ha sido reconocido como un marcador de actividad de enfermedad intersticial pulmonar difusa. Presentamos el caso de una paciente que desarrollo toxicidad pulmonar por amiodarona con niveles elevados de este nuevo marcador. Se discute la utilidad clinica de esta nueva herramienta diagnostica.

Pulmonary toxicity is an infrequent but serious adverse event in patients treated with amiodarone. The main problem at present is that we lack the necessary tools to detect this event or predict which patients will develop pulmonary toxicity. Serum Krebs von den Lungen-6 (KL-6) has been previously recognized as a marker for the activity of diffuse interstitial lung disease. We describe a patient with pulmonary toxicity due to amiodarone with increased blood levels of this new marker, and discuss the clinical usefulness of this new diagnostic tool.

Our aim was to explore the association among ACSM4 and PECI polymorphisms and AIDS progression in 454 HIV- infected patients never treated with antiretroviral drugs (146 long- term nonprogressors, 228 moderate progressors, and 80 rapid progressors). For ACSM4 polymorphisms, rs7137120 AA/AG and rs7961991 CC/CT genotypes had higher odds of having a rapid AIDS progression (odds ratio (OR) = 3.21; 95% of confidence inter- val (95% CI) = 1.26 to 8.16; P = 0.014 and OR = 3.60; 95% CI = 1.38 to 9.36; P = 0.009, respectively). Additionally, the ACSM4 haplotype integrated for both rs7961991 A and rs7137120 C alleles had higher odds of having a rapid AIDS progression (OR = 2.85; 95% CI = 1.28 to 6.25; P = 0.010). For PECI polymorphisms, no significant associations were found. In conclusion, ACSM4 polymor- phisms might play a significant role in AIDS progression.

Contains fulltext : 108229.pdf (Publisher’s version ) (Closed access) BACKGROUND: The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome (IRIS) is unclear. We aim to estimate the effect of cART on tuberculosis incidence in HIV-positive individuals in high-income countries. METHODS: The HIV-CAUSAL Collaboration consisted of 12 cohorts from the United States and Europe of HIV-positive, ART-naive, AIDS-free individuals aged ≥18 years with baseline CD4 cell count and HIV RNA levels followed up from 1996 through 2007. We estimated hazard ratios (HRs) for cART versus no cART, adjusted for time-varying CD4 cell count and HIV RNA level via inverse probability weighting. RESULTS: Of 65 121 individuals, 712 developed tuberculosis over 28 months of median follow-up (incidence, 3.0 cases per 1000 person-years). The HR for tuberculosis for cART versus no cART was 0.56 (95% confidence interval [CI], 0.44-0.72) overall, 1.04 (95% CI, 0.64-1.68) for individuals aged >50 years, and 1.46 (95% CI, 0.70-3.04) for people with a CD4 cell count of 50 years old, respectively, and 2.30 (95% CI, 1.03-5.14) for people with a CD4 cell count of 50 years old or with CD4 cell counts of

Contains fulltext : 97513.pdf (Publisher’s version ) (Closed access) BACKGROUND: Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 x 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. OBJECTIVE: To identify the optimal CD4 cell count at which cART should be initiated. DESIGN: Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 x 10(9) cells/L. SETTING: HIV clinics in Europe and the Veterans Health Administration system in the United States. PATIENTS: 20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 x 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 x 10(9) cells/L and were included in the analysis. MEASUREMENTS: Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death. RESULTS: Compared with initiating cART at the CD4 cell count threshold of 0.500 x 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. Limitations: CD4 cell count at cART initiation was not randomized. Residual confounding may exist. CONCLUSION: Initiation of cART at a threshold CD4 count of 0.500 x 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 x 10(9) cells/L.

The OK04 trial has shown that 48 weeks of lopinavir-ritonavir monotherapy with reintroduction of nucleosides as needed was noninferior to continuation of triple therapy with 2 nucleosides and lopinavir-ritonavir in patients with prior stable suppression. However, it is still uncertain if this experimental strategy can maintain suppression in the long term.Patients entered this noninferiority trial (upper limit 95% confidence interval: +12%) with no history of virological failure while receiving a protease inhibitor and receiving 2 nucleosides plus lopinavir/ritonavir, with HIV RNA50 copies per milliliter for more than 6 months. Primary end point was percent of patients without therapeutic failure, defined as confirmed HIV RNA500 copies per milliliter with exclusion of monotherapy patients who resuppressed to50 copies per milliliter after resuming baseline nucleosides, or loss to follow-up, or change of randomized therapy other than reinduction.Through 96 weeks, percentage of patient without therapeutic failure was 87% (monotherapy, n = 100) vs. 78% (triple therapy, n = 98; 95% confidence interval: -20% to +1.2%). Percentage with HIV RNA50 copies per milliliter (intention to treat, missing = failure, reinduction = failure): 77% (monotherapy) vs. 78% (triple therapy). Low-level viral rebound was more frequent in the monotherapy group. Twelve patients in the monotherapy group (12%) needed reinduction with nucleosides. Discontinuations due to adverse events were significantly more frequent in the triple therapy group (8%) than in the monotherapy group (0%); P = 0.003.At 96-week lopinavir/ritonavir monotherapy with reintroduction of nucleosides as needed was noninferior to continuation of triple therapy. Incidence of adverse events leading to treatment discontinuation was significantly lower with monotherapy. (ClinicalTrials.gov number, NCT00114933).

To study the prevalence of Delayed HIV Diagnosis (DHD) and its associated risk factors, to evaluate the effect of DHD on virological and immunological responses to HAART and to estimate the impact of DHD on all-causes mortality. Prospective cohort of 2, 564 HIV-positive HAART-naive subjects attending 19 hospitals in Spain, 2004-2006. Estimations were made by logistic regression and survival analyses by Cox regression models. Prevalence of DHD was 37.3% (35.0-39.6). DHD was related to low educational level (OR:1.31, 95% CI:1.0-1.7). Compared to men who have sex with men (MSM), DHD was more frequent in heterosexuals (OR:1.9 95% CI:1.5-2.5) and injection drug users (IDUs) (OR:2.0 95% CI:1.5-2.8). An interaction between age and sex was found. Although risk of having DHD did not increase after age 30 in women, it increased linearly with age in men. No differences in virological (OR 1.2 95% CI: 0.8-1.8) and CD4 T cell (OR 1.1 95% CI: 0.7-1.8) responses to HAART were seen. The adjusted hazard ratio for death in patients with DHD was 5.2, (95% CI: 1.9-14.5). DHD is very common, especially in older men, heterosexuals and IDUs. Although we did not find differences in virological and immunological responses to HAART, we did observe higher mortality in people with DHD. Increased efforts to early diagnose HIV infection are urgently needed.

Dyslipidemia is common in HIV-infected patients receiving antiretroviral therapy (ART) and it is often associated with the use of specific antiretroviral drugs. The phenotypic profile can include elevated triglycerides or cholesterol alone, or mixed patterns with varying changes in LDL and HDL lipoproteins, which imply different levels of cardiovascular risk. Growing evidence indicates that ART-associated hyperlipidemia accelerates the development of atherosclerosis and coronary heart disease in HIV-infected patients. In recent years, a number of retrospective database reviews and prospective cohort studies have reported a higher incidence of coronary events in patients receiving ART, which seems to be closely related with the presence of dyslipidemia and the duration of exposure to ART. Although the clinical benefit of treating ART-related dyslipidemia remains unproven, most experts recommend a policy of cardiovascular disease prevention and management similar to that used in non-HIV-infected individuals. In addition, the use of antiretrovirals associated with a more favorable lipid profile is considered. Clinical experience with lipid-lowering therapy in HIV-infected patients is still limited, but there is increasing data confirming its efficacy and safety in this setting. Drug interactions should be taken into account when statins are used in patients receiving protease inhibitors.

Background Atrial fibrillation (AF) leads to the activation of the renin-angiotensin system (RAS), which seems to play an important role in atrial remodelling. It is not known yet whether RAS blockade may prevent recurrences in patients with lone AF. Methods and results Patients with an episode of persistent AF for >7 days, in the absence of cardiac or extracardiac causes and with normal blood pressure values (`lone AF'), were recruited. Ninety patients were randomised and scheduled for electrical cardioversion. Three groups of patients were compared: Group I was treated with amiodarone 400 mg daily (30 patients), group II was treated with amiodarone 400 mg daily plus irbesartan 150 mg daily (30 patients) and group III with amiodarone 400 mg daily plus irbesartan 300 mg daily (30 patients). The primary endpoint was the time to a first recurrence of AF. The patients were cardioverted and followed. The Kaplan-Meier analysis of time to first recurrence during the follow-up period showed that patients treated with amiodarone 400 mg plus irbesartan 300 mg had a greater probability of remaining free of AF (77% vs. 52% for amiodarone and 65% for amiodarone+irbesartan 150 mg), hazard 0.27—0.82; p=0.001). ratio for a recurrence in group III: 0.47 (95% CI Conclusions The combination of irbesartan plus amiodarone decreased the rate of AF recurrences, with a dose-dependent effect, in lone AF patients.

ResumenIntroducciónLa prevalencia de la leishmaniasis visceral (LV), una parasitosis endémica en la cuenca mediterránea, puede verse afectada por movimientos migratorios.ObjetivoEl objetivo de este estudio fue analizar los casos de LV valorados en hospitales de la región de Murcia.Material y métodosSe trata de un estudio retrospectivo multicéntrico de los casos de LV diagnosticados y tratados en los diferentes hospitales de nuestra región, que se agruparon en 2 cohortes: períodoA (pA), el comprendido entre los años 1997 y 2005, y períodoB (pB), el transcurrido entre 2006 y 2013.ResultadosSe analizaron 97 casos de LV (75% fueron hombres y la edad media fue de 35 años), 36 en pA y 61 en pB; el 11% de los pacientes procedían de otros países en pA y el 22% en pB (subsaharianos en 10 casos); el 55% tenían algún tipo de inmunosupresión (80% de ellos estaban diagnosticados de infección por VIH). Las manifestaciones más frecuentes fueron: fiebre (85%) y astenia (66%). La duración media de los síntomas antes de la primera consulta fue de 47días, y el tiempo medio transcurrido entre esta primera consulta y la realización de la prueba diagnóstica, de 13días. El hallazgo más común en la exploración física fue la esplenomegalia (89%), mientras que la trombocitopenia fue el hallazgo de laboratorio más constante (78%). El diagnóstico se confirmó con la detección de amastigotes y/o PCR del aspirado medular en el 61% de los casos; en el 39% restante el aspirado fue negativo y fue necesario el estudio de otras muestras (biopsia de médula ósea, ganglio linfático, laringe, colon, parótida y amígdala, PCR en sangre, serología o inmunocromatografía en orina). El tratamiento más usado fue anfotericinaB liposomal (71%), seguida de glucantime (27%) y anfotericinaB complejo lipídico (1%); en un caso no se pudo averiguar el tratamiento administrado. Se objetivaron 16 recidivas, 11 de ellas en pacientes con sida.ConclusionesAun a riesgo de sesgos propios de estudios retrospectivos y a pesar del mejor control de la infección VIH, observamos en nuestra región un aumento en la frecuencia de casos de LV, probablemente favorecido por el aumento del número de inmigrantes.AbstractIntroductionThe prevalence of visceral leishmaniasis (VL), an endemic parasitic infection in the Mediterranean basin, can be affected by migratory movements.ObjectiveTo analyze VL cases evaluated at several hospitals in the Murcia region.MethodsRetrospective, multicentric study of VL cases; patients were grouped into two time periods: periodA (pA: 1997-2005) and periodB (pB: 2006-2013).ResultsA total of 97 VL cases were analyzed (75% men, mean age 35 years), 36 of them in pA and 61 in pB; 11% and 22% of the patients were foreigners in pA and pB, respectively (10 from sub-Saharan Africa); 55% suffered from some type of immunosuppression (80% HIV). The most common clinical manifestations were fever (85%) and asthenia (66%). The mean duration of symptoms before the first medical contact was 47 days and the average time between the first contact and the microbiological confirmation was 13 days. The most common finding on physical examination was splenomegaly (89%), whereas thrombocytopenia was the most frequent laboratory finding (78%). Diagnoses were confirmed by detection of amastigotes and/or PCR of bone marrow aspiration (BMA) in 61%; in the remaining 39% of cases, BMA was negative and additional samples were necessary (bone marrow, lymph node, larynx, colon, parotid and amygdala biopsy, PCR of blood samples, serology or urine antigen detection). The most commonly used treatment was liposomal amphotericinB (71%), followed by glucantime (27%) and amphotericinB lipid complex (1%). A total of 16 recurrent cases (11 in AIDS patients), were observed.ConclusionsAlthough this is a retrospective study and despite better control of HIV infection, we have observed an increase in the frequency of VL cases in our region, which is probably related to migratory flows.

To analyze the impact of late presentation (LP) on overall mortality and causes of death and describe LP trends and risk factors (2004-2013). Cox models and logistic regression were used to analyze data from a nation-wide cohort in Spain. LP is defined as being diagnosed when CD4 4 years, aHRLP.vs.nLP = 1.5(0.7-3.1). First-year's main cause of death was HIV/AIDS (73%); and malignancies among those surviving >4 years (32%). HIV/AIDS-related deaths were more likely in LP (59.2% vs. 25.0%; p 50.vs.

Introducción. La pielonefritis aguda (PNA) es una infección del parénquima renal que afecta con mayor frecuencia a mujeres. A pesar de que se trata de una patología habitualmente benigna se pueden producir complicaciones, algunas graves, presenta una elevada prevalencia y supone un gran consumo de recursos tanto asistenciales como económicos. Suelen estar producidas por enterobacterias, fundamentalmente, constituyendo Escherichia coli (E. coli) el principal microorganismo aislado. En los últimos años, el empleo indiscriminado de las quinolonas ha conllevado un aumento marcado de las resistencias, erigiéndose las cefalosporinas como una de las principales alternativas. Objetivos. Analizar la resistencia de E. coli a quinolonas y cefalosporinas e identificar factores de riesgo asociados. Estudiar las principales causas de reingreso y reinfección. Definir criterios de mal pronóstico y mala evolución, y comprobar su prevalencia. Creación de un modelo para predecir la resistencia de E. coli a quinolonas y mal pronóstico. Material y métodos. Estudio observacional, retrospectivo, descriptivo y con componentes analíticos, de una cohorte de pacientes ingresados con el diagnóstico de PNA a lo largo de dos años en el Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA). Se incluyeron datos epidemiológicos, analíticos, clínicos y microbiológicos. Para el análisis estadístico se utilizó el programa Statistical Package for the Social Sciences (SPSS) y para la creación de los modelos predictivos R-proyect. Resultados. La muestra la conformaron 404 pacientes de los que 87,1% fueron mujeres, con una edad media de 42,7 años. La fiebre supuso el síntoma más frecuente. Se observó una estancia hospitalaria media de 5,7 días, tratando la Unidad de Corta Estancia (UCE) al mayor número de enfermos (42,6%). Resultaron positivos 234 urocultivos (60,3%); en 177 se aisló E. coli (75,7%). La resistencia de E. coli a quinolonas fue del 18,8% y del 7,4% a cefalosporinas. Dentro de los factores de riesgo, destacaron el sexo masculino para la resistencia a quinolonas y la cirugía urinaria en las cefalosporinas. Las tasas de reinfección y reingreso fueron del 21,8% y del 16,3%, respectivamente. La reinfección se asoció, fundamentalmente, con las infecciones urinarias previas, mientras que el reingreso se precisó en pacientes renales principalmente. El 28,2% de los enfermos presentaron una mala evolución y el 49% mal pronóstico; un ingreso reciente y un Índice de Charlson alto se relacionaron con la mala evolución, y la resistencia a quinolonas y la bacteriemia en el caso del mal pronóstico; el tratamiento con cefalosporinas, por su parte, se demostró como un factor protector. Conclusiones. E. coli continúa siendo el principal agente responsable de las PNA. Actualmente, la resistencia de E. coli a quinolonas y cefalosporinas en nuestro medio se encuentra en descenso, por debajo de la media nacional y europea, aunque en el primer caso sigue siendo superior a la de otros países con un nivel de desarrollo sociosanitario similar. Sin embargo, se debe seguir evitando el uso de las quinolonas, sobre todo en varones; las cefalosporinas constituyen un tratamiento empírico adecuado para las PNA, con la excepción de pacientes sometidos a cirugías urológicas previamente. Con los modelos predictivos creados, se ha calculado una probabilidad del 60% de resistencia de E. coli a quinolonas y del 90% para mal pronóstico en pacientes que cumplen las tres condiciones: sexo masculino, ingreso en los dos meses previos e Índice de Charlson elevado. Introduction. Acute pyelonephritis (APN) is an infection of the renal parenchyma that most often affects women. Despite the fact that it is a usually benign pathology, complications can occur, some serious, it has a high prevalence and involves a large consumption of both healthcare and financial resources. They are usually produced by enterobacteria, fundamentally, Escherichia coli (E. coli) is the main isolated microorganism. In recent years, the indiscriminate use of quinolones has led to a marked increase in resistance, and cephalosporins have emerged as one of the main alternatives. Objectives. Analyze the resistance of E. coli to quinolones and cephalosporins and identify associated risk factors. Study the main causes of readmission and reinfection. Define criteria for poor prognosis and poor evolution, and check their prevalence. Creation of a model to predict resistance of E. coli to quinolones and poor prognosis. Methods. Observational, retrospective and descriptive study with analytical components of a cohort of patients admitted with the diagnosis of APN over two years at the Virgen de la Arrixaca University Clinical Hospital. Epidemiological, analytical, clinical and microbiological data were included. The SPSS program was used for the statistical analysis and predictive models was created with the R-project. Results. The sample consisted of 404 patients, of which 87.1% were women, with an average age of 42.7 years. Fever was the most frequent symptom. An average hospitalization of 5.7 days was observed and most patients were treated at the Short Stay Unit (SSU) (42.6%). 234 urine cultures (60.3%) were positive; in 177 E. coli (75.7%) was isolated. The resistance of E. coli to quinolones was 18.8% and 7.4% to cephalosporins. Among the risk factors, males stood out for resistance to quinolones and urinary surgery for cephalosporins. The reinfection and readmission rates were 21.8% and 16.3%, respectively. Reinfection was mainly associated with previous urinary infections, while readmission was required mostly in patients with renal diseases. 28.2% of the patients had a poor evolution and 49% had a poor prognosis; a recent admission and a high Charlson index were associated with poor evolution, and resistance to quinolones and bacteremia in the case of poor prognosis; treatment with cephalosporins, nevertheless, was shown to be a protective factor. Conclusions. E. coli remains the main germ responsible for APN. Currently, the resistance of E. coli to quinolones and cephalosporins in our environment is in decline, below the national and European average, although in the first case it continues to be higher than other countries with a similar social and health development level. However, the use of quinolones should continue to be avoided, especially in men; cephalosporins are an adequate empirical treatment for APN, with the exception of patients previously submitted to urological surgeries. With the predictive models created, a 60% probability of resistance of E. coli to quinolones and a 90% of poor prognosis has been calculated in patients who meet the three conditions considered: male sex, admission in the previous two months and high Charlson index.