Regular physical exercise is broadly recommended by current European and American hypertension guidelines. It remains elusive, however, whether exercise leads to a reduction of blood pressure in ...resistant hypertension as well. The present randomized controlled trial examines the cardiovascular effects of aerobic exercise on resistant hypertension. Resistant hypertension was defined as a blood pressure ≥140/90 mm Hg in spite of 3 antihypertensive agents or a blood pressure controlled by ≥4 antihypertensive agents. Fifty subjects with resistant hypertension were randomly assigned to participate or not to participate in an 8- to 12-week treadmill exercise program (target lactate, 2.0±0.5 mmol/L). Blood pressure was assessed by 24-hour monitoring. Arterial compliance and cardiac index were measured by pulse wave analysis. The training program was well tolerated by all of the patients. Exercise significantly decreased systolic and diastolic daytime ambulatory blood pressure by 6±12 and 3±7 mm Hg, respectively (P=0.03 each). Regular exercise reduced blood pressure on exertion and increased physical performance as assessed by maximal oxygen uptake and lactate curves. Arterial compliance and cardiac index remained unchanged. Physical exercise is able to decrease blood pressure even in subjects with low responsiveness to medical treatment. It should be included in the therapeutic approach to resistant hypertension.
The G1 cell cycle inhibitors tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as promising biomarkers for the prediction ...of adverse outcomes including renal replacement therapy (RRT) and mortality in critically ill adult patients who develop acute kidney injury (AKI). However, the prognostic value of urinary TIMP-2 and IGFBP7 in neonatal and pediatric AKI for adverse outcome has not been investigated yet.
The product of the urinary concentration of TIMP-2 and IGFBP7 (TIMP-2•IGFBP7) was assessed by a commercially available immunoassay (NephroCheck™) in a prospective cohort study in 133 subjects aged 0-18 years including 46 patients with established AKI according to pRIFLE criteria, 27 patients without AKI (non-AKI group I) and 60 apparently healthy neonates and children (non-AKI group II). AKI etiologies were: dehydration/hypovolemia (n = 7), hemodynamic instability (n = 7), perinatal asphyxia (n = 9), septic shock (n = 7), typical hemolytic-uremic syndrome (HUS; n = 5), interstitial nephritis (n = 5), vasculitis (n = 4), nephrotoxic injury (n = 1) and renal vein thrombosis (n = 1).
When AKI patients were classified into pRIFLE criteria, 6/46 (13%) patients fulfilled the criteria for the category "Risk", 13/46 (28%) for "Injury", 26/46 (57%) for "Failure" and 1/46 (2%) for "Loss". Patients in the "Failure" stage had a median 3.7-fold higher urinary TIMP-2•IGFBP7 compared to non-AKI subjects (P<0.001). When analyzed for AKI etiology, highest TIMP-2•IGFBP7 values were found in patients with septic shock (P<0.001 vs. non-AKI I+II). Receiver operating characteristic (ROC) curve analyses in the AKI group revealed good performance of TIMP-2•IGFBP7 in predicting 30-day (area under the curve (AUC) 0.79; 95% CI, 0.61-0.97) and 3-month mortality (AUC 0.84; 95% CI, 0.67-0.99) and moderate performance in predicting RRT (AUC 0.67; 95% CI, 0.50-0.84).
This study shows that urinary TIMP-2•IGFBP7 has a good diagnostic performance in predicting adverse outcomes in neonatal and pediatric AKI of heterogeneous etiology.
Background/Aims: Urinary biomarkers like neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) do not only allow an early diagnosis of acute kidney injury, but also ...provide prognostic information in this setting. The present prospective study investigates, whether the urinary biomarkers NGAL, KIM-1 and calprotectin have prognostic information in chronic kidney disease (CKD) as well. Methods: Urinary calprotectin, NGAL and KIM-1 concentrations were assessed in a study population of 143 patients with stable CKD comprising diabetic and hypertensive nephropathy, glomerulonephritis/vasculitis, and autosomal dominant polycystic kidney disease. An eGFR fluctuation > 5ml/min/1.73m2 in the past 12 months was defined as an exclusion criterion in order to exclude cases with acute on chronic kidney injury. Renal function was monitored for a median follow-up of 37 months. Results: In the overall study population, all the three biomarkers failed to predict DeGFR and DACR from baseline to follow-up in linear regression analysis adjusted for age, gender, and baseline eGFR. Contrarily, baseline ACR was significantly associated with DeGFR (p< 0.001). In the subgroup of patients with vasculitis and glomerulonephritis, all the three biomarkers were significantly associated with DeGFR, with calprotectin having the highest regression coefficient. Conclusion: In contrast to the traditional biomarker “albuminuria”, neither the inflammatory biomarker calprotectin, nor the tubular biomarkers NGAL and KIM-1, provide robust prognostic information on the loss or renal function in a heterogeneous CKD population. All of them, however, are candidate prognostic biomarkers in primarily inflammatory renal diseases.
Pyuria in dipstick examination serves as the most widespread screening tool for urinary tract infections (UTI). The absence of pyuria, however, does not exclude UTI. We investigated the diagnostic ...value of urinary calprotectin, a mediator protein of the innate immune system, which is released by leukocytes, for the detection of UTI and compared it with dipstick pyuria. Since even low numbers of leukocytes in the urine significantly increase urinary calprotectin concentrations, calprotectin might be a more sensitive marker than pyuria detected by dipstick. All 162 patients were prospectively included and underwent a urine dipstick, urine culture, quantification of proteinuria and determination of calprotectin in the urine. Urinary calprotectin was determined using an enzyme-linked immunosorbent assay (ELISA). UTI was defined as urine cultures with detection of one or a maximum of two uropathogenic bacteria with ≥ 10
colony-forming units per millilitre (CFU/ml). Exclusion criteria were acute kidney injury, chronic renal insufficiency and tumors of the urinary tract. 71 (43.8%) patients had a UTI. Of the 91 patients without UTI, 23 had a contamination and 19 had evidence of ≥ 10
CFU/ml considered to be asymptomatic bacteriuria. The median calprotectin concentration in patients with UTI and pyuria was significantly higher than in patients with UTI and without pyuria (5510.4 vs. 544.7 ng/ml). In ROC analyses, calprotectin revealed an area under the curve (AUC) of 0.70 for the detection of significant bacteriuria. Pyuria in dipstick examinations provided an AUC of 0.71. There was no significant difference between these AUCs in the DeLong test (p = 0.9). In patients with evidence of significant bacteriuria but without pyuria, a significantly higher calprotectin concentration was measured in the urine than in patients with neither pyuria nor UTI (544.7 ng/ml vs 95.6 ng/ml, p = 0.029). Urinary calprotectin is non-inferior to dipstick pyuria in the detection of UTI.
T cell immunity toward SARS-CoV-2 spike (S-), membrane (M-), and nucleocapsid (N-) proteins may define COVID-19 severity. Therefore, we compare the SARS-CoV-2-reactive T cell responses in moderate, ...severe, and critical COVID-19 patients and unexposed donors. Overlapping peptide pools of all three proteins induce SARS-CoV-2-reactive T cell response with dominance of CD4+ over CD8+ T cells and demonstrate interindividual immunity against the three proteins. M-protein induces the highest frequencies of CD4+ T cells, suggesting its relevance for diagnosis and vaccination. The T cell response of critical COVID-19 patients is robust and comparable or even superior to non-critical patients. Virus clearance and COVID-19 survival are not associated with either SARS-CoV-2 T cell kinetics or magnitude of T cell responses, respectively. Thus, our data do not support the hypothesis of insufficient SARS-CoV-2-reactive immunity in critical COVID-19. Conversely, it indicates that activation of differentiated memory effector T cells could cause hyperreactivity and immunopathogenesis in critical patients.
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M-, N-, and S-proteins induce T cell reactivity with differing immune dominanceM-protein triggers a strong CD4+ T cell responseICU and non-ICU COVID-19 patients have comparable SARS-CoV-2 T cell responsesViral clearance and COVID-19 survival are not associated with SARS-CoV-2 immunity
Thieme et al. demonstrate the T cell response against M-, N-, and S-proteins of SARS-CoV-2, with M-protein triggering a stronger CD4+ T cell response. ICU COVID-19 patients are capable of generating functional SARS-CoV-2 immunity non-inferior to non-ICU COVID-19 patients. SARS-CoV-2 clearance and COVID-19 survival are not associated with the magnitude of T cell response.
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