Adherence to the Mediterranean Diet in medical students.

OBJECTIVE: The protective effect of the Mediterranean Diet (MeDi) is undisputed. However, adherence to MeDi has decreased in recent years, particularly in young people. The aim of this study was to evaluate adherence to MeDi in medical students and to assess the influence of knowledge acquisition as well as other factors on dietary compliance. DESIGN: A cross-sectional study was conducted on medical students. The data were obtained through anonymous surveys that collected demographic characteristics, medical history, alcohol and tobacco consumption, physical activity and adherence to MeDi ­ using 14-point Mediterranean Diet Adherence Score (MEDAS) ­. Adherence to MeDi and related factors were evaluated by univariate and multivariable analysis. PARTICIPANTS: Medical students from the first to the sixth year of the 2018­2019 academic year. SETTING: The study was conducted at the university of Las Palmas de Gran Canaria. RESULTS: Of 589 respondents (73 % women) mean aged 22 years (range 18­39), 58·9 % showed good adherence to MeDi. Adherence was significantly associated with age (P = 0·017) but not with sex or the presence of comorbidities. Independently, adherence to MeDi was higher in last academic courses (OR = 2·1; 95 % CI = 1·3, 3·2; P = 0·001), in those who consumed alcohol more frequently (OR = 1·5; 95 % CI = 1·0, 2·1; P = 0·039) and in those who practiced more exercise (OR = 1·5; 95 % CI = 1·2, 1·9; P < 0·001). CONCLUSIONS: Half of all medical students did not have a good adherence to MeDi. Adherence was higher at older age in higher academic years and related to greater physical activity. It would be convenient to quantify dietary knowledge as well as implement nutritional educational programmes, favouring a healthy lifestyle.

Lethal Influenza in Two Related Adults with Inherited GATA2 Deficiency.

The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals. We studied two relatives who died from influenza. We Sanger sequenced GATA2 and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells. Both patients (father and son, P1 and P2) died in 2011 of H1N1pdm IAV infection at the ages of 54 and 31 years, respectively. They had not suffered from severe or moderately severe infections in the last 17 (P1) and 15 years (P2). A daughter of P1 had died at 20 years from infectious complications. Low B-cell, NK- cell, and monocyte numbers and myelodysplastic syndrome led to sequence GATA2. Patients were heterozygous for a novel, hypomorphic, R396L mutation leading to haplo-insufficiency. B- and T-cell rearrangement in peripheral blood from P1 during the influenza episode showed expansion of one major clone. No T-cell receptor excision circles were detected in P1 and P3 since they were 35 and 18 years, respectively. Both patients presented an exuberant, interferon (IFN)-γ-mediated hypercytokinemia during H1N1pdm infection. No data about patients with viremia was available. Two previously reported adult GATA2-deficient patients died from severe H1N1 IAV infection; GATA2 deficiency may predispose to life-threatening influenza in adulthood. However, a role of other genetic variants involved in immune responses cannot be ruled out. Patients with GATA2 deficiency can reach young adulthood without severe infections, including influenza, despite long-lasting complete B-cell and natural killer (NK) cell deficiency, as well as profoundly diminished T-cell thymic output.

Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection.

INTRODUCTION: Inherited variability in host immune responses influences susceptibility and outcome of Influenza A virus (IAV) infection, but these factors remain largely unknown. Components of the innate immune response may be crucial in the first days of the infection. The collectins surfactant protein (SP)-A1, -A2, and -D and mannose-binding lectin (MBL) neutralize IAV infectivity, although only SP-A2 can establish an efficient neutralization of poorly glycosylated pandemic IAV strains. METHODS: We studied the role of polymorphic variants at the genes of MBL (MBL2), SP-A1 (SFTPA1), SP-A2 (SFTPA2), and SP-D (SFTPD) in 93 patients with H1N1 pandemic 2009 (H1N1pdm) infection. RESULTS: Multivariate analysis showed that two frequent SFTPA2 missense alleles (rs1965708-C and rs1059046-A) and the SFTPA2 haplotype 1A(0) were associated with a need for mechanical ventilation, acute respiratory failure, and acute respiratory distress syndrome. The SFTPA2 haplotype 1A(1) was a protective variant. Kaplan-Meier analysis and Cox regression also showed that diplotypes not containing the 1A(1) haplotype were associated with a significantly shorter time to ICU admission in hospitalized patients. In addition, rs1965708-C (P = 0.0007), rs1059046-A (P = 0.0007), and haplotype 1A(0) (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO2/FiO2 ratio, whereas haplotype 1A(1) was associated with a higher PaO2/FiO2 ratio (P = 0.001). CONCLUSIONS: Our data suggest an effect of genetic variants of SFTPA2 on the severity of H1N1pdm infection and could pave the way for a potential treatment with haplotype-specific (1A(1)) SP-A2 for future IAV pandemics.

Role of CD39 in COVID-19 Severity: Dysregulation of Purinergic Signaling and Thromboinflammation.

CD39/NTPDase1 has emerged as an important molecule that contributes to maintain inflammatory and coagulatory homeostasis. Various studies have hypothesized the possible role of CD39 in COVID-19 pathophysiology since no confirmatory data shed light in this regard. Therefore, we aimed to quantify CD39 expression on COVID-19 patients exploring its association with severity clinical parameters and ICU admission, while unraveling the role of purinergic signaling on thromboinflammation in COVID-19 patients. We selected a prospective cohort of patients hospitalized due to severe COVID-19 pneumonia (n=75), a historical cohort of Influenza A pneumonia patients (n=18) and sex/age-matched healthy controls (n=30). CD39 was overexpressed in COVID-19 patients' plasma and immune cell subsets and related to hypoxemia. Plasma soluble form of CD39 (sCD39) was related to length of hospital stay and independently associated with intensive care unit admission (adjusted odds ratio 1.04, 95%CI 1.0-1.08, p=0.038), with a net reclassification index of 0.229 (0.118-0.287; p=0.036). COVID-19 patients showed extracellular accumulation of adenosine nucleotides (ATP and ADP), resulting in systemic inflammation and pro-coagulant state, as a consequence of purinergic pathway dysregulation. Interestingly, we found that COVID-19 plasma caused platelet activation, which was successfully blocked by the P2Y12 receptor inhibitor, ticagrelor. Therefore, sCD39 is suggested as a promising biomarker for COVID-19 severity. As a conclusion, our study indicates that CD39 overexpression in COVID-19 patients could be indicating purinergic signaling dysregulation, which might be at the basis of COVID-19 thromboinflammation disorder.

Autoantibodies against type I IFNs in patients with critical influenza pneumonia.

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients <70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10-5), but not >70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those <70 yr old (OR = 139.9, P = 3.1 × 10-10). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for ∼5% of cases of life-threatening influenza pneumonia in patients <70 yr old.

Pyogenic liver abscesses due to Escherichia coli are still related to worse outcomes.

BACKGROUND: In western countries, there has been a gradual shift from Escherichia coli to Klebsiella pneumoniae as an emerging pathogen isolated from pyogenic liver abscesses (PLA). AIMS: To compare outcomes between patients with Escherichia coli liver abscesses and non-Escherichia coli liver abscesses in terms of mortality. METHODS: One hundred nine-three consecutive hospital admissions of Pyogenic liver abscesses were analyzed, mean age 66.9 years old (± 13.6), 112 men (58%). The sample was divided into two groups: E. coli liver abscesses and non-E. coli liver abscesses. The etiologic, clinical, and microbiologic characteristics; therapeutic options; and outcomes, in terms of morbidity and mortality, between E. coli and non-E. coli liver abscesses were compared. In-hospital mortality, as outcome variable, was analyzed in a multivariate analysis. RESULTS: Fifty-seven episodes of PLA (29.5%) corresponded to E. coli infections, and 136 (70.5%) to non-E. coli infections. Patients with E. coli PLA were more likely to have jaundice, polymicrobial isolation (57.1% vs 21.6%, p < 0.001), biliary origin (71.9% vs 39%, p < 0.001), and septic shock (38.6% vs 12.5%, p < 0.001). Antibiotic therapy alone, without percutaneous drainage, was less common in the E. coli PLA group (5.3% vs 18.4%, p = 0.018). These patients also showed a higher mortality (28.1% vs 11%, p = 0.003). In multivariate analysis, E. coli isolation PLA adjusted remained as an independent factor of mortality (OR 2.6, 95%CI 1.04-6.56, p = 0.041). CONCLUSIONS: E. coli liver abscess may preclude a worse outcome than other microbiological agents, including the development of septic shock and mortality. Aggressive management must be considered.

Pyogenic liver abscesses: mortality-related factors.

GOAL: To analyse the characteristics and mortality-related factors in a series of patients hospitalized for pyogenic liver abscess (PLA). BACKGROUND: Pyogenic liver abscesses are infrequent but potentially life threatening. Factors related to mortality have been less studied. STUDY: The medical records of 84 patients, 56 men and 28 women, mean age of 64.4 years (SD: 14) who were hospitalized between 1992 and 2005 owing to a PLA were reviewed. The past medical history, clinical signs and symptoms, laboratory values, imaging studies, microbiological features, treatment, complications and mortality were recorded. Factors related to complications and mortality were analysed. RESULTS: One or more bacteria were isolated in 65 patients (77.4%), being Streptococcus spp. (40.5%), Escherichia coli (27.4%), Klebsiella spp. (14.3%) and anaerobics (17.9%) the most frequent isolates. Complications developed in 60.7% of the cases, the most common one being a right pleural effusion (34.5%). Mortality rate was 19% (95% confidence interval: 10-28%). Mortality was associated with age (P=0.005), a previous history of coronary heart disease (P=0.016), absence of fever (P=0.001), development of sepsis and/or septic shock (P<0.001), raise of bilirubin levels (P=0.004), a biliary (P=0.035), or cryptogenetic origin (P=0.039), infection owing to E. coli (P=0.01) or to Candida (P=0.009) and development of pneumonia (P<0.001). Logistic regression revealed sepsis and/or septic shock as an independent risk factor for mortality. CONCLUSIONS: Mortality associated with PLA is high. The main risk factor for mortality is the development of sepsis and/or septic shock.