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We examined the relationship between peripheral blood levels of SARS-CoV-2 S (Spike protein)1/M (Membrane protein)-reactive IFN-gamma-producing CD4+ and CD8+ T cells, serum levels of biomarkers of clinical severity, and mortality in critically ill COVID-19 patients. The potential association between SARS-CoV-2-S-Receptor Binding Domain (RBD)-specific IgG levels in sera and mortality was also investigated. SARS-CoV-2T cells and anti-RBD IgG levels were monitored in 71 non-consecutive patients (49 male and 22 female; median age, 65years) by whole-blood flow cytometry and Enzyme-linked immunosorbent assay (ELISA), respectively (326 specimens). SARS-CoV-2 RNA loads in paired tracheal aspirates [TA] (n=147) were available from 54 patients. Serum levels of interleukin-6, ferritin, D-Dimer, lactose dehydrogenase and C-reactive protein in paired sera were known. SARS-CoV-2 T cells (either CD4+, CD8+ or both) were detectable in 70 patients. SARS-CoV-2 IFN-gamma CD4+ T-cell responses were documented more frequently than their CD8+ counterparts (62 vs. 56 patients) and were of greater magnitude overall. Detectable SARS-CoV-2 S1/M-reactive CD8+ and CD4+ T-cell responses were associated with higher SARS-CoV-2 RNA loads in TA. SARS-CoV-2 RNA load in TA decreased over time, irrespective of the dynamics of SARS-CoV-2-reactive CD8+ and CD4+ T cells. No correlation was found between SARS-CoV-2 IFN-gamma T-cell counts, anti-RBD IgG concentrations and biomarker serum levels (Rho=0.3). The kinetics of both T cell subsets was comparable between those who died or survived, whereas anti-RBD IgG levels were higher across different time points in deceased patients than in survivors. Enumeration of peripheral blood levels of SARS-CoV-2-S1/M-reactive IFN-gamma CD4+ and CD8+ T cells does not predict viral clearance from the lower respiratory tract or poor clinical outcomes in critically ill COVID-19 patients. In contrast, anti-RBD IgG levels were directly associated with increased mortality. © 2022. The Author(s).

Combined kinetic analysis of plasma SARS-CoV-2 RNAemia, Nucleocapsid (N)-antigenemia and virus-specific antibodies may help ascertain the role of antibodies in preventing virus dissemination in COVID-19 patients. We performed this analysis in a cohort of 71 consecutive critically ill COVID-19 patients (49 male; median age, 65 years) using RT-PCR assay, lateral flow immunochromatography method and receptor binding domain (RBD) and N-based immunoassays. A total of 338 plasma specimens collected at a median of 12 days after symptoms onset were available for analyses. SARS-CoV-2 RNAemia and N-antigenemia were detected in 37 and 43 specimens from 26 (36.5%) and 30 (42.2%) patients, respectively. Free RNA was the main biological form of SARS-CoV-2 found in plasma. The detection rate for both viral components was associated with viral load at the upper respiratory tract. Median time to SARS-CoV-2-RBD antibody detection was 14 days (range, 4-38) from onset of symptoms. Decreasing antibody levels were observed in parallel to increasing levels of both RNAemia and N-antigenemia, yet overall a fairly modest inverse correlation (Rho = -0.35; P < 0.001) was seen between virus RNAemia and SARS-CoV-2-RBD antibody levels. The data cast doubts on a major involvement of antibodies in virus clearance from the bloodstream within the timeframe examined.

Quick Pitt (qPitt), which includes temperature, systolic blood pressure, respiratory rate, cardiac arrest, and mental status, is a new prognostic score derived from the Pitt Bacteremia score. The aim of our study is to compare qPitt with quick SOFA (qSOFA) and SOFA for scoring of severity in patients with urinary tract infection (UTI). Prospective observational study of patients diagnosed with UTI. Area under the ROC curve, sensibility, and specificity to predict 30-day mortality were calculated for qPitt, qSOFA and SOFA and compared. 382 UTI cases were analyzed. Thirty-day mortality (18.8% vs. 5.9%, p < 0.001) and longer hospital stay (6 [1-11] vs. 4 [1-7] days, p < 0.001) were associated with qPitt >= 2. However, qPitt had a worse performance to predict 30-day mortality compared to qSOFA and SOFA (AUROC 0.692 vs. 0.832 and 0.806, respectively, p = 0.010 and p = 0.041). The sensitivity of qPitt was lower than the sensitivity of qSOFA and SOFA (70.45 vs. 84.09 for both qSOFA and SOFA, p < 0.001), with a specificity lower than qSOFA and similar to SOFA (60.36 vs. 82.25 and 63.61, p < 0.001 and p = 0.742, respectively). Quick Pitt had moderate prognostic accuracy and performed worse than qSOFA and SOFA scores for predicting mortality in patients with UTI.

Human milk glycans present a unique diversity of structures that suggest different mechanisms by which they may affect the infant microbiome development. A humanized mouse model generated by infant fecal transplantation was utilized here to evaluate the impact of fucosyl-alpha 1,3-GlcNAc (3FN), fucosyl-alpha 1,6-GlcNAc, lacto-N-biose (LNB) and galacto-N-biose on the fecal microbiota and host-microbiota interactions. 16S rRNA amplicon sequencing showed that certain bacterial genera significantly increased (Ruminococcus and Oscillospira) or decreased (Eubacterium and Clostridium) in all disaccharide-supplemented groups. Interestingly, cluster analysis differentiates the consumption of fucosyl-oligosaccharides from galactosyl-oligosaccharides, highlighting the disappearance of Akkermansia genus in both fucosyl-oligosaccharides. An increment of the relative abundance of Coprococcus genus was only observed with 3FN. As well, LNB significantly increased the relative abundance of Bifidobacterium, whereas the absolute levels of this genus, as measured by quantitative real-time PCR, did not significantly increase. OTUs corresponding to the species Bifidobacterium longum, Bifidobacterium adolescentis and Ruminococcus gnavus were not present in the control after the 3-week intervention, but were shared among the donor and specific disaccharide groups, indicating that their survival is dependent on disaccharide supplementation. The 3FN-feeding group showed increased levels of butyrate and acetate in the colon, and decreased levels of serum HDL-cholesterol. 3FN also down-regulated the pro-inflammatory cytokine TNF-alpha and up-regulated the anti-inflammatory cytokines IL-10 and IL-13, and the Toll-like receptor 2 in the large intestine tissue. The present study revealed that the four disaccharides show efficacy in producing beneficial compositional shifts of the gut microbiota and in addition, the 3FN demonstrated physiological and immunomodulatory roles.

The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (R-e < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants. Analysis of 2,170 SARS-CoV-2 sequences from the first wave of the COVID-19 epidemic in Spain provides insights into transmission patterns and the effects of lockdown on the emergence of new variants.

INTRODUCTION: Quick [Sepsis-related] Sequential Organ Failure Assessment (qSOFA) is a prognostic score based on sepsis-3 definition, easy to carry out, whose application has been studied in older adults with sepsis from different sources and respiratory sepsis. However, to date no study has analysed its prognostic accuracy in older adults admitted to hospital with community urinary tract infection. METHODS: In a prospective study of 282 older adults admitted to hospital with community acquired urinary tract infection, the application of qSOFA to predict hospital mortality was analysed. The predictive capacity of qSOFA for in-hospital mortality was compared with Systemic Inflammatory Response Syndrome score (SIRS) and Sequential Organ Failure Assessment (SOFA), which require laboratory test in order to be calculated. RESULTS: In a population with a median age of 81 years, where 51.8% were males and 10.6% had septic shock, qSOFA showed sensibility and specificity of 88.46 and 75.78% and area under the receiver operating characteristic curves (AUROC) of 0.810. AUROC for qSOFA was significantly higher than that of SIRS (AUROC 0.597, P = .005) and with no statistical differences with SOFA (AUROC 0.841, P = .635). CONCLUSION: qSOFA showed a better predictive prognostic accuracy than SIRS and similar to SOFA in older adults admitted to hospital with community acquired urinary tract infection, having the advantage of not requiring laboratory tests.

Introduction Previous studies have described some risk factors for multidrug-resistant (MDR) bacteria in urinary tract infection (UTI). However, the clinical impact of MDR bacteria on older hospitalized patients with community-acquired UTI has not been broadly analyzed. We conducted a study in older adults with community-acquired UTI in order to identify risk factors for MDR bacteria and to know their clinical impact. Methods Cohort prospective observational study of patients of 65 years or older, consecutively admitted to a university hospital, diagnosed with community-acquired UTI. We compared epidemiological and clinical variables and outcomes, from UTI due to MDR and non-MDR bacteria. Independent risk factors for MDR bacteria were analyzed using logistic regression. Results 348 patients were included, 41.4% of them with UTI due to MDR bacteria. Median age was 81 years. Hospital mortality was 8.6%, with no difference between the MDR and non-MDR bacteria groups. Median length of stay was 5 [4-8] days, with a longer stay in the MDR group (6 [4-8] vs. 5 [4-7] days, p = 0.029). Inadequate empirical antimicrobial therapy (IEAT) was 23.3%, with statistically significant differences between groups (33.3% vs. 16.2%, p < 0.001). Healthcare-associated UTI variables, in particular previous antimicrobial therapy and residence in a nursing home, were found to be independent risk factors for MDR bacteria. Conclusions The clinical impact of MDR bacteria was moderate. MDR bacteria cases had higher IEAT and longer hospital stay, although mortality was not higher. Previous antimicrobial therapy and residence in a nursing home were independent risk factors for MDR bacteria.

Dog vaccination is considered an effective way of reducing Leishmania infantum infection incidence in the canine population, as well as its transmission to humans. However, the use of partially effective vaccines can have the detrimental effect of "masking" vaccinated asymptomatic carriers, capable of harbouring the parasite and transmitting it to naive individuals. After eight years on the European market, few studies have been released on CaniLeish (R) vaccine safety and efficacy. The present study, a one-year randomized CaniLeish (R) vaccine field trial, was performed in a canine leishmaniosis endemic area and included animals selected from a native dog population (n = 168). No severe adverse reactions were observed in vaccinated dogs (n = 85). Cases of active L. infantum infection were detected by serological, molecular and clinical follow-up of dogs. One-year post-vaccination, no differences in number or severity of L. infantum active infections were observed between study groups (n = 4 in each group). Vaccine-induced cellular immunity, assessed through interferon-gamma quantification, showed significantly higher levels of this cytokine one-month post-vaccination in the vaccine group (p < 0.001), but no differences were observed after nine months between trial groups (p = 0.078). These results fail to support the reported CaniLeish (R) efficacy in the prevention of active L. infantum infection in dogs from endemic areas and naturally exposed to the parasite.

Aim Risk factors for complicated community acquired Enterococcus faecalis urinary tract infection (UTI) in older patients are not well known. Methods We identified the predictive factors for E. faecalis on a cohort of 659 older patients admitted to hospital with complicated UTI. We also examined the adequacy of empirical antimicrobial therapy and outcomes in E. faecalis UTI. Multivariable logistic regression was used to identify predictors of E. faecalis UTI. Results A total of 87 (13.2%) patients had E. faecalis UTI; of these 63.2% were men, their mean age was 82.3 years and they had a great number of comorbidities. Severe sepsis or septic shock was present in 50.5%, and bacteremia was present in 26%. Indwelling urinary catheter and previous urinary instrumentation were risk factors for E. faecalis UTI by multivariate analysis (OR 2.05; 95% CI 1.15-3.65 and OR 2.16; 95% CI 1.08-4.34, respectively). Inadequate empirical antimicrobial therapy was higher in E. faecalis UTI than in UTI caused by Gram-negative microorganisms (66.6% vs 19%, P < 0.001). No significant differences in length of hospital stay or mortality were noted between E. faecalis and Gram-negative UTI. Conclusions In older patients admitted to hospital with complicated community-acquired UTI, E. faecalis should be considered for empirical treatment if the patient has a urinary catheter or previous urinary tract instrumentation in order to avoid inadequate empirical antibiotic therapy. Geriatr Gerontol Int 2019; center dot center dot: center dot center dot-center dot center dot.

Previous studies suggested that herpes simplex virus (HSV) PCR testing can be safely deferred in patients with normal cerebrospinal fluid (CSF) white blood cell (WBC) counts and protein levels as long as they are older than 2years of age and are not immunocompromised, the so-called Reller criteria. In this multicenter study, we retrospectively assessed the validity of these screening criteria in our setting. A total of 4,404 CSF specimens submitted for HSV PCR testing to the respective microbiology laboratories at the participating hospitals between 2012 and 2018 were included. Six commercially available HSV PCR assays were used across the participating centers. Ninety-one of the 4,404 CSF specimens (2.1%) tested were positive for HSV DNA (75 samples for HSV-1 and 16 for HSV-2). Nine patients failed to meet the Reller criteria, of whom seven were deemed to truly have HSV encephalitis. Overall, no significant correlation between HSV PCR cycle threshold (CT ) values and WBC counts or total protein levels was found. In addition, median HSV PCR CT s were comparable between patients who met the Reller criteria and those who did not (P=0.531). In summary, we show that HSV DNA may be detected in CSF specimens with normal WBC and protein levels collected from immunocompetent individuals older than 2years with HSV encephalitis. Nevertheless, the data also indicate that the number of cases detected could be lowered at least by half if CSF specimens with borderline WBC counts (4 cells/mm3) as well as children of any age are systematically tested.

Purpose To know the predictive factors for Pseudomonas aeruginosa (PA) urinary sepsis in hospitalised elderly patients coming from community, the adequacy of empirical antibiotic therapy and its outcomes. Methods Retrospective case-control study conducted between 2007 and 2017. Patients aged 65 years or older with PA urinary sepsis were included as cases. Three age-matched controls, with urinary sepsis caused by other microorganisms, were selected for each case. Predictors for PA urinary sepsis were determined by logistic regression analysis. Adequacy of empirical antibiotic therapy and outcomes were compared between both groups. Results A total of 332 patients, from which 83 were cases, were included. Predictive factors for PA urinary sepsis were as follows: male sex (OR 3.16, 95% CI 1.61-6.10; P

Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli are currently common in community-onset infections, limiting therapeutic options. In this work we aim to identify the prevalence of and risk factors for ESBL-producing E. coli in elderly patients with urinary tract infections (UTI) admitted to hospital.

Introduction: The clinical effect of bacteremia on outcomes in urinary tract infection (UTI) is still debated. This study aims to examine the clinical effect of bacteremia in elderly patients with UTI requiring hospital admission. Methods: This retrospective observational study recorded the clinical features, microbiology and outcomes in a Spanish cohort of patients aged >= 65 years hospitalized for UTI in whom blood cultures were performed in the emergency department. The primary outcome of the study was in-hospital mortality. Results: Of 333 patients, with a mean age of 81.6 years, 137 (41.1%) had positive blood cultures. Escherichia coli, with 223 (66.9%) cases, was the most common microorganism isolated. Independent risk factors of bacteremia were temperature >38 degrees C, heart rate >90 bpm and inversely both Enterococcus faecalis and Pseudomonas aeruginosa. Bacteremia was not associated with the length of stay in hospital (6.96 +/- 3.50 days versus 7.33 +/- 5.54 days, P = 0.456). Mortality rate was 9.3% with no significant difference between bacteremic and nonbacteremic cases (8.8% and 9.7%, respectively, P = 0.773). In-hospital mortality analyzed by logistic regression was associated with McCabe index >2 (20.5% survival versus 66.7% death, adjusted odds ratio = 6.31, 95% CI: 2.71-14.67; P < 0.001) but not with bacteremia (41.4% survival versus 38.7% death, adjusted odds ratio = 0.99, 95% CI: 0.43-2.29; P = 0.992). Conclusions: Our study suggests that the presence or absence of bacteremia in elderly people with UTI requiring hospitalization does not have an influence on outcomes such as in-hospital mortality or length of stay.

Becoming a regular smoker is a process that begins even before the first cigarette, and ends in lifelong physical and psychological dependence. Various psychological and behavioral factors contribute to this process. This article discusses smoking initiation from a comprehensive perspective, including the physiological and addictive effects of nicotine, and the personal and environmental factors that lead to smoking. Because smoking usually begins in adolescence, special emphasis is placed on this developmental stage and on the situations that encourage teenagers to smoke the first cigarette. Finally, this article analyzes the importance of the initiation process in the epidemiology and prevention of smoking. This approach may prove to be particularly useful to clinicians interested in interventions aimed to curb smoking.