The COVID-19 outbreak has had an unclear impact on the treatment and outcomes of patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to assess changes in STEMI ...management during the COVID-19 outbreak.
Using a multicenter, nationwide, retrospective, observational registry of consecutive patients who were managed in 75 specific STEMI care centers in Spain, we compared patient and procedural characteristics and in-hospital outcomes in 2 different cohorts with 30-day follow-up according to whether the patients had been treated before or after COVID-19.
Suspected STEMI patients treated in STEMI networks decreased by 27.6% and patients with confirmed STEMI fell from 1305 to 1009 (22.7%). There were no differences in reperfusion strategy (> 94% treated with primary percutaneous coronary intervention in both cohorts). Patients treated with primary percutaneous coronary intervention during the COVID-19 outbreak had a longer ischemic time (233 150-375 vs 200 140-332 minutes,
< .001) but showed no differences in the time from first medical contact to reperfusion. In-hospital mortality was higher during COVID-19 (7.5% vs 5.1%; unadjusted OR, 1.50; 95%CI, 1.07-2.11;
< .001); this association remained after adjustment for confounders (risk-adjusted OR, 1.88; 95%CI, 1.12-3.14;
= .017). In the 2020 cohort, there was a 6.3% incidence of confirmed SARS-CoV-2 infection during hospitalization.
The number of STEMI patients treated during the current COVID-19 outbreak fell vs the previous year and there was an increase in the median time from symptom onset to reperfusion and a significant 2-fold increase in the rate of in-hospital mortality. No changes in reperfusion strategy were detected, with primary percutaneous coronary intervention performed for the vast majority of patients. The co-existence of STEMI and SARS-CoV-2 infection was relatively infrequent.
Abstract
COVID-19 has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection ...in serum as a severity biomarker in COVID-19. Retrospective observational study including 193 patients admitted for COVID-19. Detection of SARS-CoV-2 RNA in serum (viremia) was performed with samples collected at 48–72 h of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19. Viremia was detected in 50–60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p < 0.001). Patients with viremia were older (p = 0.006), had poorer baseline oxygenation (PaO
2
/FiO
2
; p < 0.001), more severe lymphopenia (p < 0.001) and higher LDH (p < 0.001), IL-6 (p = 0.021), C-reactive protein (CRP; p = 0.022) and procalcitonin (p = 0.002) serum levels. We defined "relevant viremia" when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35% specificity. Relevant viremia predicted death during hospitalization (OR 9.2 3.8–22.6 for Roche, OR 10.3 3.6–29.3 for TFS; p < 0.001). Cox regression models, adjusted by age, sex and Charlson index, identified increased LDH serum levels and relevant viremia (HR = 9.87 4.13–23.57 for TFS viremia and HR = 7.09 3.3–14.82 for Roche viremia) as the best markers to predict mortality. Viremia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 patients. Viremia is highly reproducible with two different techniques (TFS and Roche), has a good consistency with other severity biomarkers for COVID-19 and better predictive accuracy.
Background. The objective of this study was to determine the impact of sustained virologic response (SVR) to pegylated interferon (peg-IFN) plus ribavirin (RBV) on the incidence of liver-related ...complications and overall mortality in human immunodeficiency virus (HIV)—infected patients with compensated hepatitis C virus (HCV)—related cirrhosis. Methods. We included in this prospective cohort study 166 coinfected patients with compensated cirrhosis, who received peg-IFN plus RBV, to assess the time from the starting date of HCV therapy to the first hepatic decompensation and death due to any cause. Results. SVR was observed in 43 (25%) individuals. Two (4.6%) patients with SVR developed liver decompensation vs 33 (26.8%) individuals without SVR (P = .002). The incidence of liver-related complications was 0.89 cases per 100 person-years (95% confidence interval CI, .11–3.1) in SVR patients and 6.4 cases per 100 person-years (95% CI, 4.5–8.9) in non-SVR patients. Factors independently associated with liver decompensation were non-SVR (hazard ratio HR, 8.1; 95% CI, 1.08–61.5; P = .042) and MELD score ≥9 at baseline (HR, 2.9; 95% CI, 1.2–7.2; P = .016). Two (4.6%) patients with SVR died due to any cause compared with 22 (17.9%) individuals without SVR (P = .02). MELD score ≥9 (HR, 3.1; 95% CI, 1.3–7.7; P = .011) and non-SVR (HR, 8.0; 95% CI, 1.07–61; P = .043) were independently associated with overall mortality. Conclusions. The achievement of SVR following peg-IFN plus RBV markedly reduces the incidence of liver-related decompensation and the overall mortality in HIV/HCV-coinfected patients with compensated cirrhosis.
To date, former research about the impact of HIV infection on mpox poor outcomes is still limited and controversial. Therefore, the aim of this study was to assess the impact of HIV on the clinical ...course of mpox, in a large population of patients from Spain. Nationwide case‐series study. Patients from 18 Spanish hospitals, with PCR‐confirmed mpox from April 27, 2022 to June 30, 2023 were included in this study. The main outcome was the development of long or complicated (LC) mpox, defined as: (i) duration of the clinical course ≥ 28 days, or; (ii) disseminated disease, or: (iii) emergence of severe complications. One thousand eight hundred twenty‐three individuals were included. Seven hundred eighty‐six (43%) were people living with HIV (PLWH), of whom 11 (1%) had a CD4 cell count < 200 cells/mm3 and 33 (3%) <350 cells/mm3. HIV viral load ≥ 1000 cp/mL was found in 27 (3%) PLWH, none of them were on effective ART. Fifteen (60%) PLWH with HIV‐RNA ≥ 1000 cp/mL showed LC versus 182 (29%) PLWH with plasma HIV‐RNA load < 1000 copies/mL and 192 (24%) individuals without HIV infection (p < 0.001). In multivariate analysis, adjusted by age, sex, CD4 cell counts and HIV viral load at the time of mpox, only plasma HIV‐RNA ≥ 1000 cp/mL was associated with a greater risk of developing LC mpox adjusted OR = 4.06 (95% confidence interval 1.57−10.51), p = 0.004. PLWH with uncontrolled HIV infection, due to lack of ART, are at a greater risk of developing LC mpox. Efforts should be made to ensure HIV testing is carried out in patients with mpox and to start ART without delay in those tested positive.
Abstract
Background
The aim of this study was to assess the impact of human immunodeficiency virus (HIV) infection on the risk of developing hepatocellular carcinoma (HCC) in patients infected with ...hepatitis C virus (HCV) who achieve sustained virological response (SVR) with direct-acting antiviral (DAA).
Methods
Multisite prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they met: (1) SVR with DAA-based combination; (2) liver stiffness (LS) ≥9.5 kPa previous to treatment; (3) LS measurement at the SVR time-point. The main endpoint was the occurrence of HCC. Propensity score (PS) was calculated to address potential confounders due to unbalanced distribution of baseline characteristics of HIV/HCV-coinfected and HCV-monoinfected patients.
Results
In total, 1035 HCV-infected patients were included, 667 (64%) coinfected with HIV. After a median (Q1–Q3) follow-up time of 43 (31–49) months, 19 (1.8%) patients developed HCC (11 3.0%; HCV-monoinfected, 81.2%; HIV/HCV-coinfected individuals; P = .013). In the multivariable analysis, HIV coinfection was associated with a lower adjusted risk of developing HCC (subhazard ratio sHR = 0.27, 95% confidence interval CI: .08–.90; P = .034). Predictors of HCC emergence were: HCV genotype 3 (sHR = 7.9, 95% CI: 2.5–24.9; P < .001), MELD score at SVR >10 (sHR = 1.37, 95% CI: 1.01–1.86; P = .043) and LS value at SVR (sHR = 1.03, 95% CI: 1.01–1.06, for 1 kPa increase; P = .011). Using inverse probability weighting method on the PS, HIV-infected patients had a lower risk of HCC (powered HR = 0.33, 95% CI: .11–.85).
Conclusions
Among HCV-infected patients with advanced fibrosis, who achieve SVR with DAA, HIV coinfection seems to be associated with a lower risk of HCC occurrence. The underlying causes for this finding need to be investigated.
Objective:
There is scarce available evidence on the distribution over time of liver complications emergence in hepatitis C virus (HCV)-infected patients who achieve sustained virological response ...(SVR) with direct-acting antiviral (DAA)-based therapy. Therefore, we aimed at describing the kinetics of liver-related events appearance in this setting.
Design:
A multicentric prospective cohort study.
Methods:
HCV-monoinfected and HIV/HCV-coinfected patients from GEHEP-011 cohort, whose inclusion criteria were had achieved SVR with DAA-based therapy; liver stiffness prior to starting treatment at least 9.5 kPa; and available liver stiffness measurement at SVR. SVR was considered as the baseline time-point.
Results:
One thousand and thirty-five patients were included, 664 (64%) coinfected with HIV. Before DAA-based therapy, 63 (6.1%) individuals showed decompensated cirrhosis. After SVR, 51 (4.9%) patients developed liver complications. Median (Q1-Q3) time to the emergence of hepatic events was hepatic encephalopathy 11 (7–24) months, ascites 14 (6–29) months, hepatocellular carcinoma (HCC) 17 (11–42) months and portal hypertension gastrointestinal bleeding (PHGB) 28 (22–38) months (
P
= 0.152). We define two profiles of liver complications: those emerging earlier (encephalopathy and ascites) and, those occurring continuously during the follow-up (HCC, PHGB) median (Q1-Q3) time to emergence 12.7 (6.6–28.2) months vs. 25.4 (12.5–41.53) months, respectively (
P
= 0.026).
Conclusion:
The vast majority of HCV-infected patients who develop liver complications after reaching SVR with DAA do it within 3 years after SVR time-point. Specifically, hepatic encephalopathy and ascites do not usually emerge after this period. Conversely, HCC and PHGB may occur in longer term. It is critical to identify patients at risk of developing hepatic events to continue performing surveillance for them.
Effective function of CD8+ T cells and enhanced innate activation of DCs in response to HIV‐1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master ...regulator TANK‐binding Kinase 1 (TBK1) might be useful to acquire controller‐like properties. Here, we evaluated the impact of the combination of 2´3´‐c´diAM(PS)2 and Poly I:C as potential adjuvants capable of potentiating DC´s abilities to induce polyfunctional HIV‐1 specific CD8+ T‐cell responses in vitro and in vivo using a humanized BLT mouse model. Adjuvant combination enhanced TBK‐1 phosphorylation and IL‐12 and IFN‐β expression on DC and increased their ability to activate polyfunctional HIV‐1‐specific CD8+ T cells in vitro. Moreover, higher proportions of hBLT mice vaccinated with ADJ‐DC exhibited less severe CD4+ T‐cell depletion following HIV‐1 infection compared to control groups. This was associated with infiltration of CD8+ T cells in the white pulp from the spleen, reduced spread of infected p24+ cells to LN, and with preserved abilities of CD8+ T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, priming of DC with PolyI:C and STING agonists might be useful for future HIV‐1 vaccine studies.
Vaccination of humanized BLT mice with DCs primed with 2’3’‐c'diAM(PS)2 and Poly I:C increased infiltration and polyfunctionality of HIV‐1‐specific CD8+ T cells into the spleen white pulp, reduced spread of infection to the LN, and less severe CD4+ T‐cell depletion after HIV‐1 infection.
We aim to describe rates and risk factors of Hepatitis C Virus (HCV) diagnoses, follow-up HCV testing and HCV seroconversion from 2004-2011 in a cohort of HIV-positive persons in Spain.
CoRIS is a ...multicentre, open and prospective cohort recruiting adult HIV-positive patients naïve to antiretroviral therapy. We analysed patients with at least one negative and one follow-up HCV serology. Incidence Rates (IR) were calculated and multivariate Poisson regression was used to estimate adjusted Rates Ratios (aIRR).
Of 2112 subjects, 53 HCV diagnoses were observed, IR = 0.93/100 py (95%CI: 0.7-1.2). IR increased from 0.88 in 2004-05 to 1.36 in 2010-11 (aIRR = 1.55; 95%CI: 0.37-6.55). In men who have sex with men (MSM) from 0.76 to 1.10 (aIRR = 1.45; 95%CI: 0.31-6.82); in heterosexual (HTX) subjects from 1.19 to 1.28 (aIRR = 1.08; 95%CI: 0.11-10.24). HCV seroconversion rates decreased from 1.77 to 0.65 (aIRR = 0.37; 95%CI: 0.12-1.11); in MSM from 1.06 to 0.49 (aIRR = 0.46; 95%CI: 0.09-2.31); in HTX from 2.55 to 0.59 (aIRR = 0.23; 95%CI: 0.06-0.98). HCV infection risk was higher for injecting drug users (IDU) compared to HTX (aIRR = 9.63;95%CI: 2.9-32.2); among MSM, for subjects aged 40-50 compared to 30 or less (IRR = 3.21; 95%CI: 1.7-6.2); and among HTX, for female sex (aIRR = 2.35; 95%CI: 1.03-5.34) and <200 CD4-count (aIRR = 2.39; 95%CI: 0.83-6.89).
We report increases in HCV diagnoses rates which seem secondary to intensification of HCV follow-up testing but not to rises in HCV infection rates. HCV IR is higher in IDU. In MSM, HCV IR increases with age. Among HTX, HCV IR is higher in women and in subjects with impaired immunological situation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) increases immune activation, inflammation, and oxidative stress that could lead to premature senescence. Different HCV ...infections, either acute or chronic infection, could lead to distinct premature cellular senescence in people living with HIV (PLWHIV). Observational study in 116 PLWHIV under antiretroviral treatment with different HCV status: (i) n = 45 chronically infected with HCV (CHC); (ii) n = 36 individuals who spontaneously clarify HCV (SC); (iii) n = 35 HIV controls. Oxidative stress biomarkers were analyzed at lipid, DNA, protein, and nitrates levels, as well as antioxidant capacity and glutathione reductase enzyme. Replicative senescence was evaluated by relative telomere length (RTL) measurement. Additionally, 26 markers of Senescence‐Associated Secretory Phenotype (SASP) were analyzed by multiplex immunoassays (Luminex xMAP technology). Differences were evaluated by generalized linear model (GLMs) adjusted by most significant covariates. The SC group had a senescence signature similar to the HIV control group and slightly lower SASP levels. However, significant differences were observed with respect to the CHC group, where an increase in the nitrate concentration adjusted arithmetic mean ratio, aAMR = 1.73 (1.27–2.35), p < 0.001, q = 0.009 and the secretion of 13 SASP‐associated factors granulocyte macrophage colony‐stimulating factor (GM‐CSF), interferon‐β, interleukin (IL)‐1β, IL‐2, IL‐8, IL‐13, tumor necrosis factor (TNF)‐α, IL‐1α, IL‐1RA, IL‐7, IL‐15, C‐X‐C motif chemokine ligand 10 (IP‐10), stem cell factor (SCF); q < 0.1) was detected. The CHC group also showed higher values of IL‐1α, IP‐10, and placental growth factor 1 (PIGF‐1) than HIV controls. The SC group showed a slightly lower senescence profile than the HIV group, which could indicate a more efficient control of viral‐induced senescence due to their immune strengths. Chronic HCV infection in PLWHIV led to an increase in nitrate and elevated SASP biomarkers favoring the establishment of viral persistence.
BACKGROUND:Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or ...lower rates of HCC treatment, and not to HIV infection itself.
AIM:To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients.
METHODS:Multicenter cohort study (1999–2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed.
RESULTS:HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (P < 0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (P = 0.001). After a median (Q1–Q3) follow-up of 11 (3–31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (P = 0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (P = 0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality adjusted hazard ratio (AHR) 1.57; 95% confidence interval0.88–2.78; P = 0.12.
CONCLUSION:HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.
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