Mycobacterium manresensis induces trained immunity in vitro.

The COVID-19 pandemic posed a global health crisis, with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants weakening vaccine-driven protection. Trained immunity could help tackle COVID-19 disease. Our objective was to analyze whether heat-killed Mycobacterium manresensis (hkMm), an environmental mycobacterium, induces trained immunity and confers protection against SARS-CoV-2 infection. To this end, THP-1 cells and primary monocytes were trained with hkMm. The increased secretion of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1ß, and IL-10, metabolic activity, and changes in epigenetic marks suggested hkMm-induced trained immunity in vitro. Healthcare workers at risk of SARS-CoV-2 infection were enrolled into the MANRECOVID19 clinical trial (NCT04452773) and were administered Nyaditum resae (NR, containing hkMm) or placebo. No significant differences in monocyte inflammatory responses or the incidence of SARS-CoV-2 infection were found between the groups, although NR modified the profile of circulating immune cell populations. Our results show that M. manresensis induces trained immunity in vitro but not in vivo when orally administered as NR daily for 14 days.

Role of renal function in cardiovascular risk assessment: A retrospective cohort study in a population with low incidence of coronary heart disease.

BACKGROUND: Early-stage chronic kidney disease (CKD), a marker of cardiovascular risk, is susceptible to therapeutic intervention but need further study in populations with low incidence of coronary heart disease (CHD). Incorporating glomerular filtration rate (GFR) could improve cardiovascular risk prediction in these patients. OBJECTIVE: To determine if decreased GFR is associated with increased risk of cardiovascular morbidity and all-cause mortality and to analyse GFR effect on cardiovascular risk prediction in a population with low CHD incidence. METHODS: Retrospective, observational, population-based study of 1,081,865 adults (35-74years old). Main exposure variable: GFR. OUTCOMES: CHD, cerebrovascular disease, cardiovascular diseases, all-cause mortality. Association between GFR categories of CKD (G1-G5) and outcomes was tested with Cox survival models. G1 was defined as the reference category. Predictive value of GFR was evaluated by integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indices. RESULTS: Beginning at stage-3a CKD, increased risk was observed for coronary (HR 1.27 (95%CI 1.14-1.43)), cerebrovascular (HR 1.19 (95%CI 1.06-1.34)), cardiovascular (HR 1.23 (95%CI 1.13-1.34)) and all-cause mortality risk (HR 1.17 (95%CI 1.07-1.27)). GFR did not increase discrimination and reclassification indices significantly for any outcome. CONCLUSION: In general population with low CHD incidence and stage-3 CKD, impaired GFR was associated with increased risk of all cardiovascular diseases studied and all-cause mortality, but adding GFR values did not improve cardiovascular risk calculation. Despite a four-fold higher rate of CHD incidence at GFR G3a compared to G1, this represents moderate cardiovascular risk in our context.

Hand-held cardiac ultrasound screening performed by family doctors with remote expert support interpretation.

OBJECTIVE: To assess the usefulness of hand-held cardiac ultrasound (HCU) performed by family doctors (FDs) in primary care, with web-based remote expert support interpretation, in a cohort of patient with symptoms or physical examination signs suggestive of cardiovascular disease. METHODS: This prospective observational study included 1312 consecutive patients, in three remote primary care areas, with symptoms or physical examination signs suggestive of cardiovascular disease. In 859 patients (group A), FDs had indicated conventional echocardiography (CE), and in 453 (Group B) the study was performed to complement the physical examination. HCU was carried out by 14 FDs after a short training period. The scans and preliminary FD reports were uploaded on a web-based program for remote expert support interpretation in <24 h. RESULTS: Experts considered HCU to be inconclusive in 116 (8.8%) patients. FD and expert agreement on diagnosis was moderate (K=0.40-0.70) except in mitral stenosis (K=0.29) and in left atrial dilation (K=0.38). Diagnostic agreement between expert interpretation and CE was good (K=0.66-0.85) except in mitral stenosis (K=0.43). After remote expert interpretation, conventional echocardiograms were finally requested by FDs in only 276 (32.1%) patients, and discharges increased by 10.2%. Furthermore, significant heart diseases were diagnosed in 32 (7%) patients of group B. CONCLUSIONS: HCU performed at the point of care by FDs with remote expert support interpretation using a web-based system is feasible, rapid and useful for detecting significant echocardiographic abnormalities and reducing the number of unnecessary echocardiographic studies.