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Background We performed a nationwide population-based retrospective study to describe the epidemiology of bacterial co-infections in coronavirus disease 2019 (COVID-19)-hospitalized patients in Spain in 2020. We also analyzed the risk factors for co-infection, the etiology and the impact in the outcome. Methods Data were obtained from records in the Minimum Basic Data Set (MBDS) of the National Surveillance System for Hospital Data in Spain, provided by the Ministry of Health and annually published with 2 years lag. COVID-19 circulated in two waves in 2020: from its introduction to 31st June and from 1st July to 31st December. The risk of developing a healthcare-associated bacterial co-infection and the risk for in-hospital and intensive care unit (ICU) mortality in co-infected patients was assessed using an adjusted logistic regression model. Results The incidence of bacterial co-infection in COVID-19 hospitalized patients was 2.3%. The main risk factors associated with bacterial co-infection were organ failure, obesity and male sex. Co-infection was associated with worse outcomes including higher in-hospital, in-ICU mortality and higher length of stay. Gram-negative bacteria caused most infections. Causative agents were similar between waves, although higher co-infections with Pseudomonas spp. were detected in the first wave and with Haemophilus influenzae and Streptococcus pneumoniae in the second. Conclusions Co-infections are not as common as those found in other viral respiratory infections; therefore, antibiotics should be used carefully. Screening for actual co-infection to prescribe antibiotic therapy when required should be performed.

Human immunodeficiency virus-1 (HIV-1) elite controllers are heterogeneous due to different immunovirological features. We aimed to identify plasma biomarkers associated with loss of spontaneous HIV-1 control in long-term elite controllers (HIV-LTECs). We performed a retrospective study in 60 HIV-LTECs [36 true-LTECs and 24 LTECs losing control (LTECs-LC)]. We selected a plasma sample from true-LTECs (towards the middle of the follow-up period) and two samples from LTECs-LC (one far from the loss of control and another close to loss of control). Plasma biomarkers were evaluated using multiplex immunoassays. The partial least squares-discriminant analysis provided the variable importance in projection (VIP), and the adjusted Generalized Linear Model provided the adjusted arithmetic mean ratio (aAMR). At the moment of the first LTECs-LC samples, the only plasma biomarker with a VIP≥1.5 was sTNF-R1, which showed higher values in LTECs-LC than true-LTECs [aAMR=1.62 (95%CI=1.20-2.19); p=0.001]. After a median of 3.9 (IQR=4.5) years of follow-up from the first sample, we also had access to a second plasma sample from 10 LTECs-LC patients. At the moment of this second LTECs-LC sample, the only plasma biomarker with VIP≥1.5 was also sTNF-R1, which showed higher values in LTECs-LC than true-LTECs [aAMR=1.93 (95%CI=1.41-2.65); p

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Additional file 2: Supplementary Table 2. Summary of adjusted associations between ambient air pollutants and hospital admissions for lower respiratory tract viral infections in Spain (2013–2015).

Supplemental material, sj-docx-4-joh-10.1177_00207314211012357 for Impact of the Economic Crisis on Endocarditis Mortality in Spain: A Nationwide Study by Christian Ortega-Loubon, Gema Ruiz López del Prado, María F. Muñoz-Moreno, Esther Gómez-Sánchez, Rocío López-Herrero, Belén Sánchez-Quirós, Mario Lorenzo-Lopez, Estefanía Gómez-Pesquera, Pablo Jorge-Monjas, Juan Bustamante-Munguira, F. Javier Álvarez, Salvador Resino, Eduardo Tamayo and María Heredia-Rodríguez in International Journal of Health Services

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Additional file 1: Supplementary Table 1. Summary of ICD-9-CM coding used for baseline comorbidities investigated in this study.

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Supplemental material, sj-docx-5-joh-10.1177_00207314211012357 for Impact of the Economic Crisis on Endocarditis Mortality in Spain: A Nationwide Study by Christian Ortega-Loubon, Gema Ruiz López del Prado, María F. Muñoz-Moreno, Esther Gómez-Sánchez, Rocío López-Herrero, Belén Sánchez-Quirós, Mario Lorenzo-Lopez, Estefanía Gómez-Pesquera, Pablo Jorge-Monjas, Juan Bustamante-Munguira, F. Javier Álvarez, Salvador Resino, Eduardo Tamayo and María Heredia-Rodríguez in International Journal of Health Services

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Supplemental material, sj-docx-3-joh-10.1177_00207314211012357 for Impact of the Economic Crisis on Endocarditis Mortality in Spain: A Nationwide Study by Christian Ortega-Loubon, Gema Ruiz López del Prado, María F. Muñoz-Moreno, Esther Gómez-Sánchez, Rocío López-Herrero, Belén Sánchez-Quirós, Mario Lorenzo-Lopez, Estefanía Gómez-Pesquera, Pablo Jorge-Monjas, Juan Bustamante-Munguira, F. Javier Álvarez, Salvador Resino, Eduardo Tamayo and María Heredia-Rodríguez in International Journal of Health Services

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Supplemental material, sj-docx-1-joh-10.1177_00207314211012357 for Impact of the Economic Crisis on Endocarditis Mortality in Spain: A Nationwide Study by Christian Ortega-Loubon, Gema Ruiz López del Prado, María F. Muñoz-Moreno, Esther Gómez-Sánchez, Rocío López-Herrero, Belén Sánchez-Quirós, Mario Lorenzo-Lopez, Estefanía Gómez-Pesquera, Pablo Jorge-Monjas, Juan Bustamante-Munguira, F. Javier Álvarez, Salvador Resino, Eduardo Tamayo and María Heredia-Rodríguez in International Journal of Health Services

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Corrigendum to "PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study" [Biomed. Pharmacother. 159 (2023) 114220]. Biomed Pharmacother. 2023 Apr 27;114803. doi: 10.1016/j.biopha.2023.114803. PMID: 37120412. Background: Patients with advanced cirrhosis are at high risk of developing clinically significant portal hypertension (CSPH). We analyzed the gene expression profile of peripheral blood mononuclear cells (PBMCs) from HIV/HCV coinfected patients to identify a gene expression signature of advanced cirrhosis with high risk for CSPH. Methods: We conducted a cross-sectional study on 68 patients. Liver stiffness measurement (LSM) was used to stratify patients into < 12.5 kPa (no cirrhosis, n = 19), 12.5 - 24.9 kPa (cirrhosis, n = 20), and ≥ 25 kPa (advanced cirrhosis with high risk for CSPH, n = 29). Besides, we further evaluated LSM < 25 kPa (n = 39) vs. ≥ 25 kPa (n = 29). Total RNA was extracted from PBMCs, and poly(A) RNA sequencing was performed. Two significant differentially expressed (SDE) transcripts were validated by quantitative PCR in a different cohort (n = 46). Results: We found 60 SDE transcripts between patients with LSM < 12.5 kPa and ≥ 25 kPa. Partial least squares discriminant analysis showed that those 60 SDE transcripts collectively discriminated LSM ≥ 25 kPa, with an area under the receiver operating characteristic curve (AUROC) of 0.84. Eight genes had an AUROC ≥ 0.75 for LSM ≥ 25 kPa: five were positively associated with LSM values (SCAMP1, ABHD17B, GPR146, GTF2A1, and TMEM64), while three were inversely associated (ZFHX2-AS1, MDK, and STAG3L2). We validated the two SDE transcripts with the highest discrimination capacity in a different cohort, finding significant differences between < 25 kPa and ≥ 25 kPa (MDK (p = 0.006) and STAG3L2 (p = 0.021)). Conclusions: A gene expression signature of 60 transcripts was associated with advanced cirrhosis with high risk for CSPH in HIV/HCV coinfected patients. This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers CP17CIII/00007 and PI18CIII/00028 to MAJS, PI17/00657 and PI20/00474 to JB, PI17/00903 and PI20/00507 to JGG, PI18CIII/00020 to AFR, and PI17CIII/00003 and PI20CIII/00004 to SR) and Ministerio de Ciencia e Innovación (AEI, PID2021-126781OB-I00 to AFR). The study was also funded by the CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU (CB21/13/00044). Sí

Gender-specific consequences after HCV eradication are unexplored. MicroRNAs (miRNAs) play a crucial role in the immune response against viral infections. However, few have highlighted miRNA role in sex-biased disease or therapy response. We aim to assess gender differences reflected in the miRNA expression of HIV/HCV-coinfected patients who achieve sustained virological response (SVR) with direct acting antivirals (DAAs). We conducted a prospective study of miRNA expression in PBMCs from 28 chronic HIV/HCV-coinfected patients (HIV/HCV) at baseline and after achieving SVR with DAAs. Sixteen HIV-monoinfected patients (HIV) and 36 healthy controls (HC) were used as controls. Identification of significant differentially expressed (SDE) miRNAs was performed with generalized linear model and mixed GLMs. We also explored putative dysregulated biological pathways. At baseline, the HIV/HCV patients showed differences in the miRNA profile concerning the HIV group (165 and 102 SDE miRNAs for males and females, respectively). Gender-stratified analysis of HIV/HCV group at baseline versus at SVR achievement showed higher differences in males (80 SDE miRNAs) than in females (55 SDE miRNAs). After SVR, HIV/HCV group showed similar values to HIV individuals, especially in females (1 SDE miRNA). However, ten miRNAs in males remained dysregulated, which were mainly involved in cancer, fatty acid, and inflammatory pathways. Taken together, our results show gender-biased dysregulation in the miRNA expression profile of PBMCs after HCV eradication with DAAs. These differences were normalized in females, while miRNA profile and their target-related pathways in males lack of normalization, which may be related to a high-risk of developing liver-related complications. This work has been supported by grants from Institute of Health Carlos III, Spain [PI15CIII/00031 and PI18CIII/00020/ to AFR and VB] and the Foundation Universidad Alfonso X el Sabio-Santander, Spain [Grant no. 1.010.932 to AFR]. AFR is supported by the Miguel Servet programme from Fondo de Investigación Sanitaria (ISCIII), Spain [CP14/CIII/00010 and CPII20CIII/0001]. This study has been conducted within the Spanish AIDS Research Network (RIS), The SPANISH AIDS Research Network – funded by the Institute of Health Carlos III (ISCIII) [RD16CIII/0002/0002]. Sí

Coinfecció pel VIH/VHC; Sistema immunitari; Teràpia amb interferó Coinfección por VIH/VHC; Sistema inmunitario; Terapia con interferón HIV/HCV coinfection; Immune system; Interferon therapy Objective To evaluate the impact of hepatitis C virus (HCV) elimination via interferon (IFN)-based therapy on gene expression profiles related to the immune system in HIV/HCV-coinfected patients. Methods We conducted a prospective study in 28 HIV/HCV-coinfected patients receiving IFN-based therapy at baseline (HIV/HCV-b) and week 24 after sustained virological response (HIV/HCV-f). Twenty-seven HIV-monoinfected patients (HIV-mono) were included as a control. RNA-seq analysis was performed on peripheral blood mononuclear cells (PBMCs). Genes with a fold-change (FC) ≥ 1.5 (in either direction) and false discovery rate (FDR) ≤ 0.05 were identified as significantly differentially expressed (SDE). Results HIV/HCV-b showed six SDE genes compared to HIV-mono group, but no significantly enriched pathways were observed. For HIV/HCV-f vs. HIV/HCV-b, we found 58 SDE genes, 34 upregulated and 24 downregulated in the HIV/HCV-f group. Of these, the most overexpressed were CXCL2, PDCD6IP, ATP5B, IGSF9, RAB26, and CSRNP1, and the most downregulated were IFI44 and IFI44L. These 58 SDE genes revealed two significantly enriched pathways (FDR

Additional file 2: Table S2. List of 4723 genes related to the immune system according to InnateDB, a public database of human immune genes ( www.innatedb.com ).

Additional file 1: Table S1. Bioinformatics pipeline to analyze raw sequences from RNA-seq of HIV/HCV-infected and HIV-monoinfected patients.

Additional file 7: Appendix S1. The GESIDA 3603b Cohort Study Group.

Additional file 5: Table S5. Summary of significant KEGG pathways (FDR ≤0.05) in the HIV/HCV-f versus HIV-mono comparison.

Additional file 4: Table S4. Summary of significant KEGG pathways (FDR ≤0.05) in the HIV/HCV-f versus HIV/HCV-b comparison.

Additional file 3: Table S3. Summary of significant differentially expressed genes (FC ≥1.5; FDR ≤0.05) in peripheral blood mononuclear cells: A) HIV/HCV-b versus HIV-mono. B) HIV/HCV-coinfected at week 24 (HIV/HCV-f) after SVR versus at baseline (HIV/HCV-b). C) HIV/HCV-f versus HIV-mono.

Additional file 6: Table S6. Summary of the most deregulated SDE genes (absolute FC ≥2 and FDR ≤0.05).

Background: A better understanding of the evolution of cirrhosis after hepatitis C virus (HCV) clearance is essential since the reversal of liver injury may not happen. We aimed to assess the evolution of plasma metabolites after direct-acting antivirals (DAAs) therapy and their association with liver disease scores in HIV/HCV-coinfected patients with advanced HCV-related cirrhosis. Methods: We performed a prospective study in 49 cirrhotic patients who started DAAs therapy. Data and samples were collected at baseline and 36 weeks after SVR. Metabolomics analysis was carried out using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Inflammation-related biomarkers were analyzed using ProcartaPlex Immunoassays. Results: At 36 weeks after SVR, patients experienced significant decrease in taurocholic acid, 2,3-butanediol, and LPC(18:0); while several phosphatidylcholines (LPC(16:1), LPC(18:1), LPC(20:4), and PC(16:0/9:0(CHO))/PC(16:0/9:0(COH)), 2-keto-n-caproic acid/2-keto-isocaproic acid and N-methyl alanine increased, compared to baseline. The plasma decrease in taurocholic acid was associated with a reduction in Child-Turcotte-Pugh (CTP) (AMR=3.39; q-value=0.006) and liver stiffness measurement (LSM) (AMR=1.06; q-value

Additional file 3. Multivariate logistic regression analysis comparing outpatients against wards patients (backward stepwise selection method/Likelihood Ratio). The association between viral RNAemia with hospitalization at the wards was evaluated adjusting by major confounding factors, but it was not selected in the final model.

Additional file 1: Table S1. Characteristics of vitamin D binding protein (DBP) polymorphisms in HIV infected patients and healthy donors.

Additional file 2: Table S2. Genetic association of vitamin D binding protein (DBP) polymorphisms with distinct patterns of AIDS progression in HIV infected patients.

Additional file 1. List of European mitochondrial DNA (mtDNA) haplogroups with their defining mutation. Adapted of Hendrickson SL, Hutcheson HB, Ruiz-Pesini E, et al. Mitochondrial DNA haplogroups influence AIDS progression. AIDS 2008; 22:2429–2439.

Background: Vitamin D is a fundamental regulator of host defenses by activating genes related to innate and adaptive immunity. In this study, we analyzed the association among single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene, with clinical patterns of AIDS progression in antiretroviral treatment (ART)-naive HIV-infected patients. Methods: We conducted a retrospective study in 667 HIV-infected patients, who were classified within three groups according to their AIDS progression pattern (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)). Five VDR SNPs (rs11568820, rs4516035, rs2228570, rs1544410, and rs7975232) were genotyped using Agena Bioscience's MassARRAY platform. Results: Significant association results were found for rs2228570. Within all HIV patients, the presence of T allele at VDR rs2228570 SNP was protective against AIDS progression (ordinal outcome) under additive (adjusted odds ratio (aOR) = 0.75; p = 0.009), dominant (aOR = 0.69; p = 0.015), and codominant (aOR = 0.56; p = 0.017) inheritance models. In addition, the same allele was protective under additive and codominant inheritance models when we compared with LTNPs vs. RPs [aOR = 0.64 (p = 0.019) and aOR = 0.37 (p = 0.018), respectively] and when we compared MPs vs. RPs [aOR = 0.72 (p = 0.035) and aOR = 0.45 (p = 0.028), respectively]. Conclusions: The VDR rs2228570 T allele was related to a lower AIDS progression pattern in ART-naive HIV-infected patients. These findings expand upon the knowledge about HIV pathogenesis in untreated HIV-infected patients with different clinical outcomes., This work has been (partially) funded by the RD16/0025/0019 and RD16CIII/0002/0002, projects as part of Accion Estrategica en Salud, Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (2013-2016) and cofinanced by Instituto de Salud Carlos III (Subdireccion General de Evaluacion) and Fondo Europeo de Desarrollo Regional (FEDER), RETIC PT17/0015/0042, Fondo de Investigacion Sanitaria (FIS) (grant number PI16/01863, PI17/01115, PI17CIII/00003), EPIICAL Project and Comunidad de Madrid B2017/BMD-3703. Programa de Investigacion de la Consejeria de Sanidad de la Comunidad de Madrid to JLJ. CIBER-BBN is an initiative funded by the VI National R& D& i Plan 2008-2011, Iniciativa Ingenio 2010, the Consolider Program, and CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. COST CA17140 Cancer Nanomedicine-Front the Bench to Bebside. AFR are supported and funded by Instituto de Salud Carlos III [grant number CP14/0010].

SUPPLEMENTARY DIGITAL CONTENT (Tables S1-S4). Table S1. International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for bacterial and fungal infections. Table S2. International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for acute organ dysfunction. Table S3. International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes used to identify the source of infection causing sepsis. Table S4. International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) coding algorithms for Charlson comorbidities. (DOCX 51 kb)

Additional file 3. Summary of full multivariate model results for the regression between mitochondrial DNA (mtDNA) haplogroups and CD4+ T cell recovery in HIV-infected patients who started combination antiretroviral therapy.

Additional file 2: Table S2. Frequencies of alleles and genotypes for IL-6 rs1800795 polymorphism in septic shock patients compared to Iberian populations in Spain from 1000 Genomes Project data ( http://www.1000genomes.org/1000-genomes-browsers ) and SIRS patients, according to type of surgery.

Additional file 3: Table S3. Adjusted risk of death regarding IL-6 rs1800795 polymorphism in septic shock patients who underwent major cardiac or abdominal surgery.

Additional file 1: Table S1. Summary of epidemiological and clinical characteristics of septic shock patients according to type of surgery.

Appendix 1. International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for comorbid diseases. Appendix 2. International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for CHC related diagnoses and abuse of alcohol and drugs. Appendix 3. International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for HIV, HCV and HBV status. Appendix 4. International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for acute organ dysfunction. Appendix 5. International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for bacterial and fungal infections. Appendix 6. International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) coding algorithms for Charlson comorbidities. (DOC 219 kb)

Additional file 1: Table S1. Summary of allelic and genotypic frequencies for TRIM5 and TRIM22 polymorphisms in HIV/HCV coinfected patients.

Additional file 1: Table S1. Methodological quality of the studies included in the meta-analysis, which was assessed using a modified score based in the Newcastle–Ottawa Scale (Stang A. Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603–605). (see Supplemental Box 2). Table S2. Meta-regression analysis for hemoglobin decline (A–C), severe anemia (D) and ribavirin dose reduction or discontinuation (E) according to ITPA polymorphisms. Box 1. Description of rs1127354/rs7270101 haplotype: ITPase deficiency ranged from absent (-) (representing wild-type activity) to mild (+), moderate (++) or severe (+++) (8, 10). Box 2. Methodological criteria used to evaluate the quality of the studies included in the meta-analysis. This score was adapted from Newcastle–Ottawa Scale (Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603–605). Figure S1. Publication bias for the rs1127354 studies included in the meta-analysis for hemoglobin decline(A), severe anemia (B) and ribavirin dose reduction or discontinuation (C) according both to Begg’s funnel plots and Egger’s test. Abbreviations: Coef., asymmetry regression coefficient; Std.Err., standard error; t, statistic; P>|t|, significance; and CI, confidence interval. Coefficients correspond to the intercept value in the regression equation, which estimates the asymmetry of the funnel plot. Positive values (Coef.> 0) indicate higher levels of effect size in studies with smaller sample sizes. Figure S2. Publication heterogeneity for studies included in the meta-analysis for hemoglobin decline: rs1127354 (A), rs7270101 (B), rs6051702 (C); severe anemia: haplotype rs1127354CC / rs7270101AA (D); and ribavirin dose reduction or discontinuation: rs1127354 (E); according to Galbraith’s plots. Abbreviations 1/s.e, precision; b/s.e, standardized effect. Figure S3. Sensitivity analysis for studies included in the meta-analysis for hemoglobin decline: rs1127354 (A), rs7270101 (B), rs6051702 (C), haplotype absent (-) vs. mild (+)/moderate (++)/severe (+++) (D), haplotype mild (+) vs. moderate (++)/severe (+++) (E) and moderate (++) vs. severe (+++) (F). Sensitivity analyses were carried out to investigate the influence of any one study on the overall meta-analysis by sequential omission of individual studies. Figure S4. Forest plot of the meta-analysis performed to investigate the association between ITPA rs6051702 polymorphisms and hemoglobin decline, included in the Hwang, et al. Article (32). Abbreviations: CI, confidence intervals; OR, odds ratio. Figure S5. Sensitivity analysis for studies included in the meta-analysis for severe anemia: rs1127354 (A), haplotype absent (-) vs. mild (+)/moderate (++)/severe (+++) (B) and haplotype mild (+) vs. moderate (++)/severe (+++) (C). Sensitivity analyses were carried out to investigate the influence of any one study on the overall meta-analysis by sequential omission of individual studies. Figure S6. Sensitivity analysis for studies included in the meta-analysis for ribavirin dose reduction or discontinuation: rs1127354 (A), haplotype absent (-) vs. mild (+)/moderate (++)/severe (+++) (B), haplotype mild (+) vs. moderate (++)/severe (+++) (C) and moderate (++) vs. severe (+++) (D). Sensitivity analyses were carried out to investigate the influence of any one study on the overall meta-analysis by sequential omission of individual studies.

Additional file 4. Multivariate logistic regression analysis comparing wards patients against ICU patients (backward stepwise selection method/Likelihood Ratio). The association between viral RNAemia and viral RNA load with critical illness was evaluated adjusting by major confounding factors.

Additional file 1. Recruited patients in each hospital.

Additional file 2. Multivariate logistic regression analysis comparing outpatients against wards patients (Enter method). The association between viral RNAemia with hospitalization at the wards was evaluated adjusting by major confounding factors.

Additional file 1. Recruited patients in each hospital.

Additional file 5. Laboratory parameters levels across groups.

Additional file 5. Laboratory parameters levels across groups.