Three-Year Mortality of Older Hospitalized Patients with Osteosarcopenia: Data from the OsteoSys Study.

Osteosarcopenia, the concurrent presence of sarcopenia and osteopenia/osteoporosis, poses a significant health risk to older adults, yet its impact on clinical outcomes is not fully understood. The aim of this prospective, longitudinal multicentre study was to examine the impact of osteosarcopenia on 3-year mortality and unplanned hospitalizations among 572 older hospitalized patients (mean age 75.1 ± 10.8 years, 78% female). Sarcopenia and low bone mineral density (BMD) were evaluated using Dual Energy X-ray Absorptiometry and the European Working Group on Sarcopenia in Older People (EWGSOP2) and WHO criteria, respectively. Among participants, 76% had low BMD, 9% were sarcopenic, and 8% had osteosarcopenia. Individuals with osteosarcopenia experienced a significantly higher rate of mortality (46%, p < 001) and unplanned hospitalization (86%, p < 001) compared to those without this condition. Moreover, "healthy" subjects-those without sarcopenia or low BMD-showed markedly lower 3-year mortality (9%, p < 001) and less unplanned hospitalization (53%, p < 001). The presence of osteosarcopenia (p = 0.009) increased the 3-year mortality risk by 30% over sarcopenia alone and by 8% over low BMD alone, underscoring the severe health implications of concurrent muscle and bone deterioration. This study highlights the substantial impact of osteosarcopenia on mortality among older adults, emphasizing the need for targeted diagnostic and therapeutic strategies.

Prevalence of masked hypertension in attended versus unattended office blood pressure measurement.

There is a controversial debate regarding whether unattended blood pressure (BP) measurement should be regarded as the new gold standard of office BP measurement. Unattended BP measurement eliminates the white-coat effect and reduces external influences on the patient. On the other hand, it might underestimate real-life BP. The present study compares the prevalence of masked hypertension using attended versus unattended office BP measurements. We performed a cross-sectional study on 213 patients in a general practitioner's outpatient clinic and compared attended and unattended office BP with 24h-ambulatory BP monitoring (24h-ABPM). Masked hypertension was defined as pressure ≥135/85 mmHg in daytime ABPM with office systolic BP < 140/90 mmHg. Median attended and unattended office BPs were 140/86 and 134/80 mmHg with a median 24h-BP of 129/79 mmHg and daytime ABP of 133/82 mmHg. The number of patients with masked hypertension was 45/213 (21.2%) using unattended and 23/213 (10.8%) using attended office BP measurements (p < .0001). Bland-Altman analysis revealed a 7.4 mmHg systolic and 6.2 mmHg diastolic bias between the attended versus unattended office BP, and two systolic and -1.7 mmHg diastolic biases between the unattended office BP and daytime ambulatory BP. In linear regression analysis, an unattended office BP of 134 mmHg corresponded to 140 mmHg in attended BP measurement. Using a cut-off of 135/85 mmHg instead of 140/90 mmHg in unattended office BP measurement, the rate of masked hypertension was 26/213 (12.2%). Thus, unattended office BP measurement results in a substantial increase in the prevalence of masked hypertension using the traditional definition of hypertension. The present findings suggest that it might be reasonable to use a definition of 135/85 mmHg.

Predictors of blood pressure response to continuous positive airway pressure treatment in patients with sleep apnea.

BACKGROUND: Sleep apnea is associated with hypertension. Metaanalyses indicate that treatment of sleep apnea by continuous positive airway pressure (CPAP) reduces blood pressure (BP) by a mean of 3 mmHg. To date, predictors of BP response to CPAP remain incompletely understood. We hypothesized that the magnitude of CPAP-induced BP reduction depends on baseline apnea-hypopnea index (AHI) and the extent of daytime sleepiness. METHODS: We performed a retrospective study on the association of BP response to CPAP with polysomnographic readings, intensity of sleepiness (measured by Epworth Sleepiness Scale, ESS), and epidemiologic parameters in 2461 patients with obstructive sleep apnea. BP response was defined as the difference between office BP at polysomonography examinations before and after initiation of CPAP. RESULTS: Five hundred and fifty-five patients fulfilled all inclusion and exclusion criteria and were included in the analysis. Median monthly CPAP usage was 143.7 h (85.4-204.1 h). BP was significantly higher at baseline than at follow-up (129.9 ±â€Š15.5 vs. 128.3 ±â€Š15.2, P  = 0.021) resulting in mean reduction of BP of -1.5 ±â€Š19.2 mmHg. patients with a higher than median baseline AHI (median 21) showed a more pronounced reduction of BP than those with lower AHI (AHI ≥21: 130.5 ±â€Š15.3 vs. 128.6 ±â€Š14.6, P  = 0.06; AHI <21: 129.5 ±â€Š15.8 vs. 127.9 ±â€Š15.8, P  = 0.18). CPAP therapy led to a significant reduction in sleepiness (8.3 ±â€Š4.8 vs. 6.6 ±â€Š4.5, P  < 0.0001). Those subjects with higher than median sleepiness score (ESS ≥8), however, did not show a significant difference in BP response compared with those with a lower sleepiness score. Receiver-operating characteristic (ROC) curve analyses investigating the accuracy of AHI and ESS to predict a BP reduction at least 5 mmHg revealed an AUC of 0.51 and 0.52, respectively. CONCLUSION: The study confirms that CPAP therapy for sleep apnea has a mild BP lowering effect. Although this effect is slightly higher in patients with above-average AHI, neither AHI nor ESS can be used to define threshold values predicting a BP decrease at least 5 mmHg.

Oxidized high-density lipoprotein associates with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common heart arrhythmia and considered to be a progressive chronic disease associated with increased morbidity and mortality. Recent data suggest a link between inflammation, oxidative stress, and AF, although the underlying mechanisms are not fully understood. Because oxidized lipoproteins cause structural damage and electrophysiologic changes in cardiomyocytes, it is feasible that the transformation of atheroprotective high-density lipoprotein (HDL) into dysfunctional HDL contributes to the development of AF. OBJECTIVE: The purpose of this study was to determine whether a reduced antioxidant function of HDL is associated with the presence of AF. METHODS: In this multicenter cross-sectional cohort study, we assessed HDL function in sera of 1206 participants. Patients were divided into groups according to the presence of AF (n = 233) or no AF (n = 973). A validated cell-free biochemical assay was used to determine reduced HDL antioxidant function as assessed by increased normalized HDL lipid peroxide content (nHDLox). RESULTS: Participants with AF had a 9% higher mean relative nHDLox compared to persons without AF (P = .025). nHDLox was strongly associated with AF in all models of logistic regression, including the analysis adjusted for age, sex, and risk factors for AF (all P ≤.01). CONCLUSION: Reduced antioxidant HDL function is associated with the presence of AF, which supports growing evidence that impaired lipoprotein function is linked to electrophysiological changes in cardiomyocytes. nHDLox is one of several contributors to the initiation and perpetuation of AF.

Plasma NGAL levels in stable kidney transplant recipients and the risk of allograft loss.

BACKGROUND: The objective of this study was to investigate the utility of neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin (CPT) to predict long-term graft survival in stable kidney transplant recipients (KTR). METHODS: A total of 709 stable outpatient KTR were enrolled >2 months post-transplant. The utility of plasma and urinary NGAL (pNGAL, uNGAL) and plasma and urinary CPT at enrollment to predict death-censored graft loss was evaluated during a 58-month follow-up. RESULTS: Among biomarkers, pNGAL showed the best predictive ability for graft loss and was the only biomarker with an area under the curve (AUC) > 0.7 for graft loss within 5 years. Patients with graft loss within 5 years (n = 49) had a median pNGAL of 304 [interquartile range (IQR) 235-358] versus 182 (IQR 128-246) ng/mL with surviving grafts (P < .001). Time-dependent receiver operating characteristic analyses at 58 months indicated an AUC for pNGAL of 0.795, serum creatinine-based Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) had an AUC of 0.866. pNGAL added to a model based on conventional risk factors for graft loss with death as competing risk (age, transplant age, presence of donor-specific antibodies, presence of proteinuria, history of delayed graft function) had a strong independent association with graft loss {subdistribution hazard ratio (sHR) for binary log-transformed pNGAL [log2(pNGAL)] 3.4, 95% confidence interval (CI) 2.24-5.15, P < .0001}. This association was substantially attenuated when eGFR was added to the model [sHR for log2(pNGAL) 1.63, 95% CI 0.92-2.88, P = .095]. Category-free net reclassification improvement of a risk model including log2(pNGAL) in addition to conventional risk factors and eGFR was 54.3% (95% CI 9.2%-99.3%) but C-statistic did not improve significantly. CONCLUSIONS: pNGAL was an independent predictor of renal allograft loss in stable KTR from one transplant center but did not show consistent added value when compared with baseline predictors including the conventional marker eGFR. Future studies in larger cohorts are warranted.

Increased SARS-CoV-2 reactive low avidity T cells producing inflammatory cytokines in pediatric post-acute COVID-19 sequelae (PASC).

BACKGROUND: A proportion of the convalescent SARS-CoV-2 pediatric population presents nonspecific symptoms, mental health problems, and a reduction in quality of life similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 symptomatic. However, data regarding its clinical manifestation and immune mechanisms are currently scarce. METHODS: In this study, we perform a comprehensive clinical and immunological profiling of 17 convalescent COVID-19 children with post-acute COVID-19 sequelae (PASC) manifestation and 13 convalescent children without PASC manifestation. A detailed medical history, blood and instrumental tests, and physical examination were obtained from all patients. SARS-CoV-2 reactive T-cell response was analyzed via multiparametric flow cytometry and the humoral immunity was addressed via pseudovirus neutralization and ELISA assay. RESULTS: The most common PASC symptoms were shortness of breath/exercise intolerance, paresthesia, smell/taste disturbance, chest pain, dyspnea, headache, and lack of concentration. Blood count and clinical chemistry showed no statistical differences among the study groups. We detected higher frequencies of spike (S) reactive CD4+ and CD8+ T cells among the PASC study group, characterized by TNFα and IFNγ production and low functional avidity. CRP levels are positively correlated with IFNγ producing reactive CD8+ T cells. CONCLUSIONS: Our data might indicate a possible involvement of a persistent cellular inflammatory response triggered by SARS-CoV-2 in the development of the observed sequelae in pediatric PASC. These results may have implications on future therapeutic and prevention strategies.

Macrophage migration inhibitory factor receptor CD74 expression is associated with expansion and differentiation of effector T cells in COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused millions of COVID-19 cases and deaths worldwide. Severity of pulmonary pathologies and poor prognosis were reported to be associated with the activation non-virus-specific bystander T cells. In addition, high concentrations of the macrophage migration inhibitory factor (MIF) were found in serum of COVID-19 patients. We hypothesized that these two pathogenic factors might be related and analyzed the expression of receptors for MIF on T cells in COVID-19. T cells from PBMCs of hospitalized patients with mild and severe COVID-19 were characterized. A significantly higher proportion of CD4+ and CD8+ T cells from COVID-19 patients expressed CD74 on the cell surface compared to healthy controls. To induce intracellular signaling upon MIF binding, CD74 forms complexes with CD44, CXCR2, or CXCR4. The vast majority of CD74+ T cells expressed CD44, whereas expression of CXCR2 and CXCR4 was low in controls but increased upon SARS-CoV-2 infection. Hence, T cells in COVID-19 patients express receptors that render them responsive to MIF. A detailed analysis of CD74+ T cell populations revealed that most of them had a central memory phenotype early in infection, while cells with an effector and effector memory phenotype arose later during infection. Furthermore, CD74+ T cells produced more cytotoxic molecules and proliferation markers. Our data provide new insights into the MIF receptor and co-receptor repertoire of bystander T cells in COVID-19 and uncovers a novel and potentially druggable aspect of the immunological footprint of SARS-CoV-2.

Fading SARS-CoV-2 humoral VOC cross-reactivity and sustained cellular immunity in convalescent children and adolescents.

Cross-reactive cellular and humoral immunity can substantially contribute to antiviral defense against SARS-CoV-2 variants of concern (VOC). While the adult SARS-CoV-2 cellular and humoral immunity and its cross-recognition potential against VOC is broadly analyzed, similar data regarding the pediatric population are missing. In this study, we perform an analysis of the humoral and cellular SARS-CoV-2 response immune of 32 convalescent COVID-19 children (children), 27 convalescent vaccinated adults(C + V+) and 7 unvaccinated convalescent adults (C + V-). Similarly to adults, a significant reduction of cross-reactive neutralizing capacity against delta and omicron VOC was observed 6 months after SARS-CoV-2 infection. While SAR-CoV-2 neutralizing capacity was comparable among children and C + V- against all VOC, children demonstrated as expected an inferior humoral response when compared to C + V+. Nevertheless, children generated SARS-CoV-2 reactive T cells with broad cross-recognition potential. When compared to V + C+, children presented even comparable frequencies of WT-reactive CD4 + and CD8 + T cells with high avidity and functionality. Taking into consideration the limitations of study - unknown disease onset for 53% of the asymptomatic pediatric subjects, serological detection of SARS-CoV-2 infection-, our results suggest that following SARS-CoV-2 infection children generate a humoral SARS-CoV-2 response with neutralizing potential comparable to unvaccinated COVID-19 convalescent adults as well a sustained SARS-CoV-2 cellular response cross-reactive to VOC.

Severity of neurological Long-COVID symptoms correlates with increased level of autoantibodies targeting vasoregulatory and autonomic nervous system receptors.

BACKGROUND: The Long-COVID syndrome constitutes a plethora of persisting symptoms with neurological disorders being the most disabling ones. The pathogenesis of Long-COVID is currently under heavy scrutiny and existing data on the role of auto-immune reaction to G-protein coupled receptors (GPCR) are conflicting. METHODS: This monocentric, cross-sectional study included patients who suffered a mild to moderate SARS-CoV-2 infection up to 12 months prior to enrollment with (n = 72) or without (n = 58) Long-COVID diagnosis according to the German S1 guideline or with no known history of SARS-CoV-2 infection (n = 70). While autoantibodies specific for the vasoregulation associated Adrenergic Receptor (ADR) B1 and B2 and the CNS and vasoregulation associated muscarinic acetylcholine receptor (CHR) M3 and M4 were measured by ELISA, neurological disorders were quantified by internationally standardized questionnaires. RESULTS: The prevalence and concentrations of evaluated autoantibodes were significantly higher in Long-COVID compared to the 2 other groups (p = 2.1*10-9) with a significantly higher number of patients with simultaneous detection of more than one autoantibody in the Long-COVID group (p = 0.0419). Importantly, the overall inflammatory state was low in all 3 groups. ARB1 and ARB2 correlated negatively CERAD Trail Marking A and B (R ≤ -0.26, p ≤ 0.043), while CHRM3 correlated positively with Chadler Fatigue Scale (R = 0.37, p = 0.0087). CONCLUSIONS: Concentrations of autoantibodies correlates to the intensity of neurological disorders including psychomotor speed, visual search, attention, and fatigue.

Dysfunctional high-density lipoprotein in chronic inflammatory rheumatic diseases.

Background: The mechanism explaining low cholesterol concentrations in chronic inflammatory rheumatic disease (CIRD) is incompletely understood. We hypothesized that chronic inflammation impairs the functionality of high-density lipoprotein (HDL), for example, by oxidative processes. Objectives: Assessment of oxidized HDL (HDLox), a marker of dysfunctional HDL, in newly diagnosed patients with CIRD before and after initiation of immunosuppressive therapy and comparison of HDLox values of patients with CIRD to non-CIRD controls. Design: Prospective observational trial. Methods: The study was conducted on 44 newly diagnosed CIRD patients, who were initiated on immunosuppressive therapy (baseline). A total of 136 patients without CIRD served as control. Lipid profiles including HDLox levels and C-reactive protein (CRP) were measured in both groups at baseline. In CIRD patients, measurements were repeated 12 weeks after baseline. Validated outcome tools for disease activity and function were assessed at baseline and 12 weeks. Results: A total of 33 (75%) patients with rheumatoid arthritis, 7(16%) with axial spondyloarthritis, and 4 (9%) with systemic lupus erythematosus were included. Groups were comparable for age and BMI. CIRD patients had higher HDLox concentrations (1.57 versus 0.78, p = 0.02) and tended to have lower low-density lipoprotein cholesterol, HDL cholesterol, and cholesterol concentrations compared to controls. HDLox (1.57 versus 1.4, p = 0.26) and CRP levels (2.1 versus 0.7 mg/dl, p < 0.01) decreased in CIRD patients from baseline to follow-up. Conclusion: CIRD is associated with an impairment of the anti-inflammatory properties of HDL as reflected by an increase in HDLox concentrations. This effect may contribute to the increased cardiovascular risk in chronic inflammatory diseases.

Empagliflozin Reduces Interleukin-6 Levels in Patients with Heart Failure.

Background: The inhibition of sodium-glucose co-transporter 2 (SGLT-2) has been shown to be beneficial in the treatment of diabetic and non-diabetic patients with heart failure. The underlying mechanisms are incompletely understood. The present prospective study investigates for the first time the effect of empagliflozin on various soluble markers of inflammation in patients with reduced ejection fraction (HFrEF). Methods: We included 50 inpatients with HFrEF and diabetes mellitus type 2. A total of 25 patients received a therapy with the SGLT-2-inhibitor empagliflozin in addition to standard medication; the other 25 patients did not receive empagliflozin and were considered the control group. Quality of life, functional status and soluble immunological parameters in serum were assessed at baseline and after 3 months. Results: The baseline characteristics of both groups revealed no significant differences. Patients on empagliflozin demonstrated a significant improvement in the Minnesota living with heart failure questionnaire (baseline 44.2 ± 20.2 vs. 24 ± 17.7; p < 0.001), in distance in the 6-min walk test (baseline 343 ± 145 m vs. 450 ± 115 m; p < 0.001) and in soluble interleukin-6 level (baseline 21.7 ± 21.8 pg/mL vs. 13.7 ± 15.8 pg/mL; p = 0.008). There was no significant change of these or other parameters in the control group (p > 0.05 each). Conclusions: The empagliflozin-induced improvement of quality of life and functional capacity in patients with HFrEF and type 2 diabetes mellitus is accompanied by a substantial reduction of interleukin-6 levels. Thus, anti-inflammatory effects may contribute to the benefits of SGLT-2-inhibitors in heart failure.

Low avidity circulating SARS-CoV-2 reactive CD8+ T cells with proinflammatory TEMRA phenotype are associated with post-acute sequelae of COVID-19.

The role of adaptive SARS-CoV-2 specific immunity in post-acute sequelae of COVID-19 (PASC) is not well explored, although a growing population of convalescent COVID-19 patients with manifestation of PASC is observed. We analyzed the SARS-CoV-2-specific immune response, via pseudovirus neutralizing assay and multiparametric flow cytometry in 40 post-acute sequelae of COVID-19 patients with non-specific PASC manifestation and 15 COVID-19 convalescent healthy donors. Although frequencies of SARS-CoV-2-reactive CD4+ T cells were similar between the studied cohorts, a stronger SARS-CoV-2 reactive CD8+ T cell response, characterized by IFNγ production and predominant TEMRA phenotype but low functional TCR avidity was detected in PASC patients compared to controls. Of interest, high avidity SARS-CoV-2-reactive CD4+ and CD8+ T cells were comparable between the groups demonstrating sufficient cellular antiviral response in PASC. In line with the cellular immunity, neutralizing capacity in PASC patients was not inferior compared to controls. In conclusion, our data suggest that PASC may be driven by an inflammatory response triggered by an expanded population of low avidity SARS-CoV-2 reactive pro-inflammatory CD8+ T cells. These pro-inflammatory T cells with TEMRA phenotype are known to be activated by a low or even without TCR stimulation and lead to a tissue damage. Further studies including animal models are required for a better understanding of underlying immunopathogensis. Summary: A CD8+ driven persistent inflammatory response triggered by SARS-CoV-2 may be responsible for the observed sequelae in PASC patients.

Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019.

It has recently been shown that von Willebrand factor (VWF) multimers contribute to immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, whether the generation of autoantibodies to ADAMTS13 contributes to this finding. In this observational prospective controlled multicenter study blood samples and clinical data of patients hospitalized for COVID-19 were collected from April to November 2020. The study included 156 individuals with 90 patients having confirmed COVID-19 of mild to critical severity. 30 healthy individuals and 36 critically ill ICU patients without COVID-19 served as controls. ADAMTS13 antibodies occurred in 31 (34.4%) COVID-19 patients. Antibodies occurred more often in critically ill COVID-19 patients (55.9%) than non-COVID-19 ICU patients and healthy controls (5.6% and 6.7%; p < 0.001), respectively. Generation of ADAMTS13 antibodies in COVID-19 was associated with lower ADAMTS13 activity (56.5%, interquartile range (IQR) 21.25 vs. 71.5%, IQR 24.25, p = 0.0041), increased disease severity (severe or critical in 90% vs. 62.3%, p = 0.019), and a trend to higher mortality (35.5% vs. 18.6%, p = 0.077). Median time to antibody development was 11 days after first positive SARS-CoV-2-PCR specimen. Gel analysis of VWF multimers resembled the constellation in patients with TTP. The present study demonstrates for the first time, that generation of ADAMTS13 antibodies is frequent in COVID-19, associated with lower ADAMTS13 activity and increased risk of an adverse disease course. These findings provide a rationale to include ADAMTS13 antibodies in the diagnostic workup of SARS-CoV-2 infections.

Oscillometric pulse wave analysis for detecting low flow arteriovenous fistula.

BACKGROUND: Pulse wave analysis may be useful to assess fistula function. We aimed to prospectively evaluate if convenient oscillometric devices are applicable to detect flow below 500 ml/min in a real life clinical setting. METHODS: Pulse waves were recorded ambilaterally with the vicorder® device at the brachial artery in 53 patients on haemodialysis with native fistula. Primary variables consisted of the mean slope between the systolic maximum and the diacrotic notch (Slope2), the sum of the mean slopes in the four characteristic sections of pulse waves (Slope∑) and the amplitude of relative volumetric change in the measuring cuff at the upper arm (AMP). Fistula flow was measured with the use of duplex sonography using a standardized approach. RESULTS: Parameter values above or below the median indicated measurement at the non-fistula side, with sensitivities/specificities of 0.79/0.79 (p < 0.001) for Slope 2, 0.64/0.64 (p = 0.003) for Slope∑ and 0.81/0.81 (p < 0.001) for AMP if measurements at the fistula and non-fistula arm were considered. ROC-analyses of parameter values measured at the fistula to detect low flow demonstrated AUCs (with CI) of 0.652 (0.437-0.866, p = 0.167) for Slope2, 0.732 (0.566-0.899, p = 0.006) for Slope∑ and 0.775 (0.56-0.991, p = 0.012) for AMP. The point with maximal youden's index was regarded as optimal cut-off, which corresponded to sensitivities and specificities of 0.8/0.56 for slope2, 0.86/ 0.56 for Slope∑ and 0.93/0.78 for AMP. CONCLUSION: Functional surveillance with oscillometry is a promising clinical application to detect a low fistula flow. Among all investigated pulse wave parameters AMP revealed the highest diagnostic accuracy.

Case report: SARS-CoV-2 specific T-cells are associated with myocarditis after COVID-19 vaccination with mRNA-1273.

Vaccination of SARS-CoV-2 with BNT162b2 or mRNA-1273 both have a low incidence of induction of myocarditis. Here we report on utilizing adaptive immune receptor repertoire sequencing (AIRR-Seq) as a way to assess the specificity of tissue infiltrating immune cells.

Association of plasma propionate concentration with coronary artery disease in a large cross-sectional study.

Background: Microbiome has been linked to the pathogenesis of coronary artery disease (CAD) but data providing direct evidence for an association of short-chain fatty acids (SCFA) with CAD are lacking. This study aimed to evaluate the role of propionate, the most important SCFA in patients with CAD. Methods: We performed a cross-sectional study enrolling patients admitted for invasive coronary angiography in two university hospitals in Germany. Patients with known or suspected CAD and risk factors for cardiovascular disease were prospectively recruited. Blood sampling was performed after overnight fasting and before invasive procedures. Measurement of propionate was performed by liquid chromatography. Results: The study included 1,253 patients (median [IQR], 67 [58-76] years; 799 men [64%]). A total of 739 had invasively confirmed CAD with at least one coronary artery stenosis ≥50% and 514 had exclusion of CAD. CAD patients had significant lower levels of propionate (median 5.75 µM, IQR, 4.1-7.6) compared to the non-CAD groups 6.53 µM (4.6-8.6, p < 0.001). Multivariate linear regression analysis revealed an odds ratio of 0.94 (CI 0.90-0.98, p = 0.002) for propionate as predictor of CAD. The odds ratio was further decreased to 0.45 (CI 0.31-0.65, p < 0.001) when comparing patients in the lowest quartile of propionate with those with higher levels of propionate. Conclusion: The study provides large-scale in vivo data for the association of propionate to manifest coronary artery disease, independent of other traditional cardiovascular risk factors.

Use and effectiveness of remdesivir for the treatment of patients with covid-19 using data from the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS): a multicentre cohort study.

OBJECTIVES: The use of remdesivir (RDV) as the first drug approved for coronavirus disease 2019 (COVID-19) remains controversial. Based on the Lean European Open Survey on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected patients (LEOSS), we aim to contribute timing-focused complementary real-world insights to its evaluation. METHODS: SARS-CoV-2 infected patients between January 2020 and December 2021 treated with RDV were matched 1:1 to controls considering sociodemographics, comorbidities and clinical status. Multiple imputations were used to account for missing data. Effects on fatal outcome were estimated using uni- and multivariable Cox regression models. RESULTS: We included 9,687 patients. For those starting RDV administration in the complicated phase, Cox regression for fatal outcome showed an adjusted hazard ratio (aHR) of 0.59 (95%CI 0.41-0.83). Positive trends could be obtained for further scenarios: an aHR of 0.51 (95%CI 0.16-1.68) when RDV was initiated in uncomplicated and of 0.76 (95% CI 0.55-1.04) in a critical phase of disease. Patients receiving RDV with concomitant steroids exhibited a further reduction in aHR in both, the complicated (aHR 0.50, 95%CI 0.29-0.88) and critical phase (aHR 0.63, 95%CI 0.39-1.02). CONCLUSION: Our study results elucidate that RDV use, in particular when initiated in the complicated phase and accompanied by steroids is associated with improved mortality. However, given the limitations of non-randomized trials in estimating the magnitude of the benefit of an intervention, further randomized trials focusing on the timing of therapy initiation seem warranted.

Urinary biomarkers to predict acute kidney damage and mortality in COVID-19.

INTRODUCTION: Acute kidney injury (AKI) is a frequent condition in patients hospitalized for COVID-19. There are only a few reports on the use of urinary biomarkers in COVID-19 and no data so far comparing the prognostic use of individual biomarkers in the prediction of adverse outcomes. MATERIALS AND METHODS: We performed a prospective mono-centric study on the value of urinary biomarkers in predicting the composite endpoint of a transfer to the intensive care unit, the need for renal replacement therapy, mechanical ventilation, and in-hospital mortality. 41 patients hospitalized for COVID-19 were enrolled in this study. Urine samples were obtained shortly after admission to assess neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), calprotectin, and vascular non-inflammatory molecule-1 (vanin-1). RESULTS: We identified calprotectin as a predictor of a severe course of the disease requiring intensive care treatment (AUC 0.728, p = 0.016). Positive and negative predictive values were 78.6% and 76.9%, respectively, using a cut-off concentration of 127.8 ng/mL. NGAL tended to predict COVID-19-associated AKI without reaching statistical significance (AUC 0.669, p = 0.053). The best parameter in the prediction of in-hospital mortality was NGAL as well (AUC 0.674, p = 0.077). KIM-1 and vanin-1 did not reach significance for any of the investigated endpoints. CONCLUSION: While KIM-1 and vanin-1 did not provide prognostic clinical information in the context of COVID-19, the present study shows that urinary calprotectin is moderately predictive of the need for intensive care unit (ICU) admission, and NGAL may be modestly predictive of AKI in COVID-19. Calprotectin and NGAL show promise as potential helpful adjuncts in the identification of patients at increased risk of poor outcomes or complications in COVID-19.