Attenuation of COVID-19-induced cytokine storm in a young male patient with severe respiratory and neurological symptoms.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), produces protean manifestations and causes indiscriminate havoc in multiple organ systems. This rapid and vast production of proinflammatory cytokines contributes to a condition termed cytokine storm. A 35-year-old, otherwise healthy, employed, male patient was tested positive for COVID-19. He was admitted to the hospital on disease day 10 due to retarded verbal reactions and progressive delirium. On account of these conditions and the need for noninvasive/invasive ventilation, a combination treatment with baricitinib and remdesivir in conjunction with standard of care was initiated. The cytokine storm was rapidly blocked, leading to a vast pulmonary recovery with retarded recovery of the central nervous system. We conclude that the rapid blockade of the COVID-19-induced cytokine storm should be considered of avail as a principle of careful decision-making for effective recovery.

Correction to: Serum levels of sclerostin reflect altered bone microarchitecture in patients with hepatic cirrhosis.

Correction to: Wien Klin Wochenschr 2019 https://doi.org/10.1007/s00508-019-01595-8 The original version of this article unfortunately contained a mistake. The last sentence should read: Patients with ALD had significantly lower sclerostin levels, compared to controls. The authors apologize for the ….

Serum levels of sclerostin reflect altered bone microarchitecture in patients with hepatic cirrhosis.

BACKGROUND: Patients with hepatic cirrhosis are at increased risk of bone loss. Recent work on areal bone mineral density has reported contradictory findings. As the assessment of bone microarchitecture is complex, a search was made for correlations with new serum markers of bone turnover. Current data on serum sclerostin levels in patients with increased fracture risk are divergent and to date only one study has examined patients with hepatic cirrhosis. Therefore, the aim of this study was to evaluate serum sclerostin levels and to test for correlations with microarchitecture. METHODS: This study was performed in 32 patients with recently diagnosed hepatic cirrhosis and 32 controls. The parameters of bone microarchitecture were assessed by high-resolution peripheral quantitative computed tomography. Sclerostin was detected via a new ELISA that detects the active receptor interaction site at loop 2 of the sclerostin core region. RESULTS: Sclerostin levels were slightly, but not significantly lower in the patient group, compared to controls. In contrast, patients with alcoholic liver cirrhosis had significantly lower levels than the controls. A significant correlation with areal bone mineral density (BMD) and trabecular microarchitecture was observed in the patient group. However, there was hardly any correlation between sclerostin and bone microarchitecture in the controls. CONCLUSION: In hepatic cirrhosis, sclerostin is related to altered bone microarchitecture and lower areal BMD. In alcoholic liver disease, low sclerostin concentrations were seen.

Serum level of IP-10 increases predictive value of IL28B polymorphisms for spontaneous clearance of acute HCV infection.

BACKGROUND & AIMS: Single nucleotide polymorphisms (SNPs) in IL28B and serum levels of interferon γ inducible protein 10 (IP-10) predict outcomes of antiviral therapy in patients with chronic hepatitis C. We associated IL28B SNPs rs12979860 and rs8099917, along with serum levels of IP-10, with outcomes of patients with acute hepatitis C (AHC). METHODS: We studied 120 patients with AHC (64 male; 37 ± 16 years old) and 96 healthy individuals (controls). The IL28B SNPs rs12979860 and rs8099917 were detected using real-time polymerase chain reaction; serum concentrations of IP-10 were measured by enzyme-linked immunosorbent assays of 62 patients with AHC. RESULTS: Hepatitis C virus was cleared spontaneously from 59 patients (49.2%). The IL28B rs12979860 C/C genotype was more frequent among patients with AHC than controls (62.5% vs 39.6%; P < .001) and among patients with spontaneous clearance than those without (74.6% vs 51.7%; P = .02) (positive predictive value, 60.3%). Patients with IL28B rs12979860 C/C more frequently developed jaundice (53.2% vs 27.6%; P = .022) than carriers of the T allele. The median level of IP-10 was lower among patients with AHC and spontaneous clearance (764 [113-2470] pg/mL) than those without spontaneous clearance (1481 [141-4412] pg/mL; P = .006). Based on receiver operating characteristic analysis, 540 pg/mL IP-10 was set as the cutoff for patients most likely to have spontaneous clearance (positive predictive value, 71.4%; negative predictive value, 65.9%). Including data on IP-10 levels increased the ability of the IL28B rs12979860 C/C to identify patients most likely to have spontaneous clearance (83% of those who had an IP-10 level <540 pg/mL and 32% who had an IP-10 level >540 pg/mL) (P < .01). CONCLUSIONS: The combination of serum level of IP-10 and SNPs in IL28B can identify patients with AHC who are most likely to undergo spontaneous clearance and those in need of early antiviral therapy.

Alkaline phosphatase predicts relapse in chronic hepatitis C patients with end-of-treatment response.

AIM: To investigate relapse predictors in chronic hepatitis C (CHC) patients with end-of-treatment response (ETR), after pegylated interferon-alpha (PegIFN-alpha) and ribavirin treatment. METHODS: In a retrospective study we evaluated a spectrum of predictors of relapse after PegIFN-alpha and ribavirin treatment in 86 CHC patients with ETR. Viral loads were determined with real-time reverse transcription polymerase chain reaction. Hepatitis C virus genotyping was performed by sequencing analysis. Patients with genotype 1 were treated for 48 wk with 180 microg PegIFN-alpha2a or 1.5 microg/kg PegIFN-alpha2b once weekly plus ribavirin at a dosage of 1000 mg/d for those under 75 kg or 1200 mg/d for those over 75 kg. Patients with genotypes 2 and 3 were treated for 24 wk with 180 microg PegIFN-alpha2a or 1.5 microg/kg PegIFN-alpha2b once weekly plus ribavirin at a dosage of 800 mg/d. RESULTS: In all ETR patients, binary logistic regression analysis identified absence of complete early virological response (cEVR) (OR 27.07, 95% CI: 3.09-237.26, P < 0.005), serum alkaline phosphatase (ALP) levels prior to therapy < 75 U/L (OR: 6.16, 95% CI: 2.1-18.03, P < 0.001) and body mass index > 26 kg/m(2) (OR: 8.27, 95% CI: 2.22-30.84, P < 0.005) as independent predictors of relapse. When cEVR patients were analyzed exclusively, ALP prior to therapy < 75 U/L remained the only predictor of relapse. CONCLUSION: Lower levels of ALP prior to, during and after therapy seem to be associated with a higher risk of relapse in CHC patients with ETR.

Serum levels of N-terminal pro-B-type natriuretic peptide are associated with allograft function in recipients of renal transplants.

BACKGROUND: B-type natriuretic peptide (BNP) plays a key role in the regulation of volume homeostasis, and elevated blood levels of BNP are associated with end-stage renal disease. Renal transplantation leads to a decrease of elevated BNP levels with established graft function. Assessment of N-terminal pro-BNP (NT-proBNP) is established as reflecting volume homeostasis, and we therefore studied the relationship between NT-proBNP and allograft function in a prospective study. METHODS: NT-proBNP was assessed in 76 patients with end-stage renal disease undergoing renal transplantation. Patients were grouped according to immediate or delayed graft function. The degree of allograft function was assessed from the estimated glomerular filtration rate according to the MDRD formula. RESULTS: In patients with immediate graft function (n = 48), median NT-proBNP decreased immediately after transplantation; in patients with delayed function (n = 28), median NT-proBNP first increased and then decreased as function improved. Patients with early acute rejection showed significantly higher NT-proBNP levels prior to transplantation than patients without rejection. NT-proBNP levels measured 2 or 3 weeks post-transplant were significantly correlated with the estimated glomerular filtration rate 1 year after transplantation. CONCLUSIONS: An association was observed between renal allograft function and post-transplant levels of NT-proBNP. The association was not found to be a useful general predictor for graft function in individual patients in a clinical setting, as the range of NT-proBNP levels measured was too wide.

Impact of smoking on progression of vascular diseases and patient survival in type-1 diabetic patients after simultaneous kidney-pancreas transplantation in a single centre.

We evaluated the impact of smoking on the progression of macro-angiopathy as well as patient and graft survival in 35 type-1 diabetic patients with simultaneous kidney-pancreas transplantation (SKPT). According to their smoking history, the patients were divided into smokers (n = 12) and nonsmokers (n = 23). Mean observation period was 80 (12-168) vs. 84 (12-228) months. The prevalence of vascular diseases as well as the incidence of vascular complications during the observation period was evaluated in each group. Graft- and patient survival were calculated. The prevalence of all vascular diseases was higher in the smokers with prior SKPT at the start as also at the end of study; however, the differences were not significant. In addition, the incidence of vascular complications (stroke, myocardial infarction and amputation) during the follow-up period was higher in the smoking group. Taking all vascular complications together (events/patient/year) the difference was significant (0.105 vs. 0.066, P < 0.05). One- and 5-year patient survival was 100% and 75% for smokers vs. 100% and 91% for nonsmokers. One- and 5-year pancreas graft survival at the same time was 100% and 75% in living smokers as well as 100% and 83% in the nonsmokers: We conclude that smoking after SKPT is associated with a progression of macro-angiopathy. Additionally, mortality after SKPT tends to be higher in smoking patients.

Hyperthyroidism affects arterial stiffness, plasma NT-pro-B-type natriuretic peptide levels, and subendocardial perfusion in patients with Graves' disease.

BACKGROUND: Arterial stiffness is thought to play a critical role in the pathogenesis of cardiovascular events, and in hyperthyroidism increased cardiovascular event rates have been reported. AIM: To investigate markers of systemic arterial stiffness, volume homeostasis, and subendocardial perfusion and its interrelationship in patients with Graves' disease (GD) in hyperthyroidism and euthyroidism. METHOD: Aortic augmentation index (AIx@75) as a measure of systemic arterial stiffness and subendocardial viability ratio (SEVR) as a surrogate measure of subendocardial perfusion were assessed by applanation tonometry in 59 patients with GD in hyperthyroidism and euthyroidism, and measurements were compared to plasma levels of NT-pro-B-type natriuretic peptide (NT-ProBNP). RESULTS: AIx@75 and NT-ProBNP levels were significantly increased in hyperthyroidism compared to euthyroidism and were positively correlated with each other. SEVR was significantly decreased in hyperthyroidism compared to euthyroidism, mainly due to increased heart rates as shown by the heart rate-corrected SEVR75. CONCLUSIONS: In hyperthyroidism, patients with GD exhibited increased systemic arterial stiffness, paralleled by increased levels of NT-ProBNP, a marker of volume overload. The decreased subendocardial perfusion in hyperthyroidism seemed to be mainly due to increased heart rates. The observed unfavorable hemodynamic alterations in hyperthyroidism may serve to explain increased cardiovascular event rates in patients with GD.

Diurnal variation of pulse wave velocity assessed non-invasively by applanation tonometry in young healthy men.

PURPOSE: Pulse wave velocity (PWV) is at least partially controlled by vascular tone. Vascular tone and underlying physiological processes such as sympathetic activity, plasma catecholamin, and cortisol levels have been shown to follow diurnal variations. MATERIALS AND METHODS: Carotid-to-radial PWV was non-invasively assessed by applanation tonometry in 21 young (26.5+/-2.3 years) healthy men at three different time points (8:00 hr, 12:00 hr, 17:00 hr) during a day. Additionally, heart rate, systolic, diastolic and mean blood pressure, and radial pulse pressure were assessed at the same time points. RESULTS: The mean PWV was significantly higher at 8:00 hr compared with the mean PWV assessed at later time points. No significant differences were found between mean PWV at 12:00 hr and at 17:00 hr. When PWV was corrected for blood pressure, the difference between values at 8:00 hr and 12:00 hr was no longer significant. Systolic, diastolic and mean blood pressure were significantly lower at 17:00 hr compared with those at 8:00 hr. CONCLUSION: A small but significant diurnal variation of PWV was observed in young healthy men, which might have been caused at least partly by variations of blood pressure. This finding could be of value, when PWV is used in human research. Thus, in longitudinal investigations the measurements should be performed at similar time points in the course of a day, in order to obtain comparable data. Additionally, our observations ought to be of assistance to studies in which novel pharmacological compounds with activity on the vasculature are investigated.

Prevalence, severity and predictors of HOMA-estimated insulin resistance in diabetic and nondiabetic patients with end-stage renal disease.

BACKGROUND: Prevalence of insulin resistance (IR) is increased in type 2 diabetes and in end-stage renal disease (ESRD). IR is associated with advanced atherosclerosis and is an independent predictor for cardiovascular disease in diabetes and ESRD patients. We investigated prevalence, severity, predictors and relation to vascular diseases by the homeostasis model assessment (HOMA-IR) in diabetic and nondiabetic ESRD patients. METHODS: ESRD patients with type 2 diabetes (n = 27) and nondiabetic ESRD patients (n = 35) were included in the study. IR was assessed with the HOMA-IR using fasting glucose and insulin levels. Additionally, serum levels of C-peptide, HbA1c, triglycerides, cholesterol and C-reactive protein and blood pressure were assessed. RESULTS: Median HOMA-IR was significantly higher in the diabetic ESRD patients than in the nondiabetic ESRD patients (6.3 [range 0.7-61.7] vs. 2.4 [range 0.3-5.7]; p < 0.001). Systolic blood pressure and triglycerides were significantly higher in patients with higher HOMA-IR, whereas HDL cholesterol was significantly lower in those patients. Only nondiabetic patients with increased HOMA-IR had significantly higher C-peptide levels than those with lower HOMA-IR (14.9 + 5.7 vs. 9.0 + 4.3, p = 0.004). Vascular disease prevalence was significantly higher in diabetic patients with higher HOMA-IR than in those with lower HOMA-IR. CONCLUSIONS: Prevalence and severity of HOMA-IR was greater in diabetic ESRD patients than in those without diabetes. In diabetic patients low HDL cholesterol was the only predictor for higher HOMA-IR, whereas in nondiabetic patients a high C-peptide level was the only predictor for higher HOMA-IR. The prevalence of vascular diseases is associated with higher HOMA-IR in ESRD patients.

Genotyping of the lactase-phlorizin hydrolase -13910 polymorphism by LightCycler PCR and implications for the diagnosis of lactose intolerance.

BACKGROUND: Hypolactasia and lactose intolerance are common conditions worldwide. Hypolactasia seems to be strongly correlated with genotype C/C of the genetic variant C-->T(-13910) upstream of the lactase phlorizin hydrolase (LPH) gene. We developed a rapid genotyping assay for LPH C-->T(-13910) and investigated the relationship of positive lactose breath hydrogen test (LBHT) results suggesting lactose intolerance with LPH C-->T(-13910) genotype. METHODS: Using automated DNA purification on the MagNA Pure LC and real-time PCR on the LightCycler, we examined samples from 220 individuals to estimate genotype frequencies; we then determined LPH C-->T(-13910) genotype in samples from 54 Caucasian patients with a positive LBHT result and symptoms of lactose intolerance. RESULTS: Genotyping of 220 individuals revealed frequencies of 21.4%, 41.8%, and 36.8% for genotypes C/C, C/T, and T/T. Of the patients with positive LBHT results, only 50% had the C/C genotype suggestive of primary adult hypolactasia in our study population. The other patients had various degrees of secondary hypolactasia or symptoms of lactose intolerance. Patients with C/C genotype had a mean (SD) peak H2 increase in the LBHT [108 (58) ppm] that was significantly higher than in patients with the C/T [65 (54) ppm] and T/T [44 (34) ppm] genotypes. CONCLUSIONS: The new real-time PCR assay provides a rapid, labor-saving means for the genotyping of LPH C-->T(-13910). Use of the assay may assist in differentiating patients with primary hypolactasia from those with secondary hypolactasia and lactose intolerance, who may need further clinical examinations to diagnose their underlying primary diseases.

Diurnal variation of arterial stiffness and subendocardial perfusion noninvasively assessed using applanation tonometry in healthy young men.

BACKGROUND: Arterial stiffness is at least partially controlled by vascular tone. Vascular tone and underlying physiological processes, e.g. sympathetic activity, have been shown to follow diurnal variations. METHODS: This study investigated whether arterial stiffness and perfusion of subendocardial myocardium relative to cardiac workload show diurnal variations under physiological conditions. The aortic augmentation index (AIx) and subendocardial viability ratio (SEVR) were measured noninvasively in 26 healthy young men (27.6 +/- 3.4 years) using applanation tonometry at three different times (8:00, 12:00, 17:00) during one day. RESULTS: Mean AIx was significantly higher and mean SEVR significantly lower at 8:00 than at the later times. No significant differences were found between mean AIx and mean SEVR at 12:00 and at 17:00. CONCLUSIONS: The observed diurnal variations of AIx and SEVR will be of value when applanation tonometry is used in human research. In order to arrive at comparable data in longitudinal investigations, measurements should be made at similar times during the course of a day. In addition, our observation should assist in studies in which novel pharmacological compounds with activity on the vasculature are investigated.

Type 2 diabetes in patients with end-stage renal disease is not associated with further increased serum inflammatory parameters.

BACKGROUND: Cardiovascular morbidity and mortality is markedly increased in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) and is further pronounced when diabetes mellitus is also present. As atherogenesis is mediated by inflammation of vessel walls and as evidence evolves that atherosclerosis and diabetes mellitus share a common inflammatory basis, we considered whether ESRD patients with additional diabetes mellitus exhibit increased inflammation levels exceeding those of ESRD patients without diabetes mellitus. METHODS: The study included 20 ESRD patients with type 2 diabetes mellitus and 16 non-diabetic ESRD patients on long-term HD. The patients' clinical characteristics and serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), soluble tumor necrosis factor receptor I (sTNF-RI), neopterin and fibrinogen were assessed. RESULTS: There were no significant differences in serum levels of CRP, IL-6, neopterin, sTNF-RI and fibrinogen found in ESRD patients with and without diabetes mellitus. HD duration correlated significantly with neopterin (r=0.515, p<0.001) and sTNF-RI (r=0.429, p<0.05) serum levels. HD led to a significant reduction in neopterin levels whereas CRP, IL-6 and sTNF-RI levels did not change significantly. CONCLUSIONS: With the inherent limitations of a small number of patients studied, we observed that the presence of type 2 diabetes mellitus in addition to ESRD was not associated with further increased serum levels of the examined inflammatory parameters. Our observations suggest that the worsened prognosis of diabetic ESRD patients is probably not explainable by superimposing inflammatory processes.