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Background MicroRNAs are small, endogenous, non-coding RNAs that regulate the expression of many genes. It has recently been shown that circulating microRNAs may be biomarkers of hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy (HCM). Objective To determine whether circulating levels of microRNAs involved in HCM are associated with electrocardiographic and echocardiographic parameters. Methods This study enrolled 20 patients with familial HCM and 20 blood donors. Peripheral serum levels of miR-29a-3p, miR-199a-5p and miR-451a were assessed by quantitative real-time polymerase chain reaction and compared with levels in the control group. Whether circulating levels of miRNAs in HCM patients correlated with electrocardiographic and echocardiographic parameters was also assessed. Results Median circulating levels of miR-29a and miR-451a were significantly higher in HCM than the control group. Median miR-199a levels did not differ between groups. However, circulating levels of miR-199a negatively correlated with corrected QT duration (Bazett formula). Median miR-29a levels positively correlated with QRS duration. In addition, circulating levels of miR-29a correlated with maximal wall thickness, left ventricular mass index and left atrial volume index. Conclusions The data suggested that serum levels of miR-29a and miR-451a were significantly increased in HCM patients. As the circulating level of miR-29a correlated with QRS duration, left ventricular hypertrophy and left atrial dilatation, the serum miR-199a level negatively correlated with corrected QT duration. These miRNAs may be seen as potential biomarkers for further research in HCM pathophysiology.

Vitamin D contributes to blood pressure (BP) regulation. We compared the association of BP in diabetic patients with either total vitamin D - the standard way of analyzing the vitamin D status - or free vitamin D, because only free vitamin D passes the cell membrane and interacts with the nuclear vitamin D receptor (VDR). An analytical cross-sectional study was conducted with 178 diabetic patients with impaired kidney function. Free and total vitamin D concentrations were measured in all patients. Multiple linear regression analysis considering patient age, sex, body mass index, height, smoking and drinking situation, the use of antihypertensive drugs, cholecalciferol treatment, C-reactive protein and estimated glomerular filtration rate as confounding factors were conducted to compare the association of free and total vitamin D with systolic and diastolic blood pressure (SBP and DBP). Multiple linear regression analysis revealed that neither SBP nor DBP was correlated with total vitamin D (SBP, 95% CI -0.405 ~ 0.159, p = 0.390; DBP, 95% CI -0.131 ~ 0.142, p = 0.933) (Table 2). However, the concentration of free vitamin D was independently associated with SBP (95% CI -2.691 ~ -0.210; p = 0.022) (Table 3), but not with DBP (95% CI -0.934 ~ 0.285; p = 0.293). In conclusion, free - but not total - vitamin D serum concentrations in patients with diabetes and impaired kidney function are inversely correlated with SBP. This study suggests that free vitamin D measurements might be more clinically relevant - as compared to measurements of total vitamin D - to adjust vitamin D therapy in diabetic patients with impaired kidney function.

Objective: In this study, we aimed to compare the functional adaptations of the left ventricle in variant forms of left ventricular hypertrophy (LVH) and to evaluate the use of two-dimensional speckle tracking echocardiography (2D-STE) in differential diagnosis and prognosis. Methods: This was a prospective cohort study of 68 patients with LVH, including 20 patients with non-obstructive hypertrophic cardiomyopathy (HCM), 23 competitive top-level athletes free of cardiovascular disease, and 25 patients with hypertensive heart disease (HHD). All the subjects underwent 2D transthoracic echocardiography (TTE) and 2D-STE. The primary endpoint was all-cause mortality. Global longitudinal strain (GLS) below −12.5% was defined as severely reduced strain, −12.5% to −17.9% as mildly reduced strain, and above −18% as normal strain. Results: The mean LV-GLS value was higher in athletes than in patients with HCM and HHD with the lowest value being in the HCM group (HCM: −11.4±2.2%; HHD: −13.6±2.6%; and athletes: −15.5±2.1%; p

BACKGROUND We aimed to compare the clinical and laboratory characteristics and imaging methods of patients diagnosed with preseptal cellulitis and orbital cellulitis in the pediatric age group. METHODS The study was designed retrospectively, and the medical records of all patients who were hospitalized with the diagnosis of preseptal cellulitis and orbital cellulitis were reviewed. The findings of preseptal cellulitis and orbital cellulitis groups were compared. The risk factors for the development of orbital involvement were analyzed. RESULTS A total of 123 patients were included, 90.2% with preseptal cellulitis and 9.8% with cellulitis. The male gender ratio was 60.2%, and the mean age was 72 ± 43 months. While all patients had eyelid swelling and redness, 20.3% had fever. Ocular involvement was 51.2% in the right eye and 4.9% in both eyes. The most common predisposing factor was rhinosinusitis (56.1%). Radiological imaging (computed tomography/magnetic resonance imaging) was performed in 83.7% of the patients. Subperiostal abscess was detected in 7 cases (5.6%) in which three of the cases were managed surgically and four were treated with medically. The levels of C-reactive protein were significantly higher in patients with orbital involvement (P = 0.033), but there was no difference between the presence of fever, leukocyte and platelet values. CONCLUSIONS Rhinosinusitis was the most common predisposing factor in the development of preseptal cellulitis and orbital cellulitis. Orbital involvement was present in 9.8% of the patients. It was determined that high C-reactive protein value could be used to predict orbital involvement.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin-25 are involved in catalytic iron-related kidney injury after cardiac surgery with cardiopulmonary bypass. We explored the predictive value of plasma NGAL, plasma hepcidin-25, and the plasma NGAL:hepcidin-25 ratio for major adverse kidney events (MAKE) after cardiac surgery. Methods: We compared the predictive value of plasma NGAL, hepcidin-25, and plasma NGAL:hepcidin-25 with that of serum creatinine (Cr) and urinary output and protein for primary-endpoint MAKE (acute kidney injury [AKI] stages 2 and 3, persistent AKI >48 hours, acute dialysis, and in-hospital mortality) and secondary-endpoint AKI in 100 cardiac surgery patients at intensive care unit (ICU) admission. We performed ROC curve, logistic regression, and reclassification analyses. Results: At ICU admission, plasma NGAL, plasma NGAL:hepcidin-25, plasma interleukin-6, and Cr predicted MAKE (area under the ROC curve [AUC]: 0.77, 0.79, 0.74, and 0.74, respectively) and AKI (0.73, 0.89, 0.70, and 0.69). For AKI prediction, plasma NGAL:hepcidin-25 had a higher discriminatory power than Cr (AUC difference 0.26 [95% CI 0.00-0.53]). Urinary output and protein, plasma lactate, C-reactive protein, creatine kinase myocardial band, and brain natriuretic peptide did not predict MAKE or AKI (AUC

Background Acute kidney injury (AKI) subtypes combining kidney functional parameters and injury biomarkers may have prognostic value. We aimed to determine whether neutrophil gelatinase-associated lipocalin (NGAL)/hepcidin-25 ratio (urinary concentrations of NGAL divided by that of hepcidin-25) defined subtypes are of prognostic relevance in cardiac surgery patients. Methods We studied 198 higher-risk cardiac surgery patients. We allocated patients to four groups: Kidney Disease Improving Global Outcomes (KDIGO)-AKI-negative and NGAL/hepcidin-25 ratio-negative (no AKI), KDIGO AKI-negative and NGAL/hepcidin-25 ratio-positive (subclinical AKI), KDIGO AKI-positive and NGAL/hepcidin-25 ratio-negative (clinical AKI), KDIGO AKI-positive and NGAL/hepcidin-25 ratio-positive (combined AKI). Outcomes included in-hospital mortality (primary) and long-term mortality (secondary). Results We identified 127 (61.6%) patients with no AKI, 13 (6.6%) with subclinical, 40 (20.2%) with clinical and 18 (9.1%) with combined AKI. Subclinical AKI patients had a 23-fold greater in-hospital mortality than no AKI patients. For combined AKI vs. no AKI or clinical AKI, findings were stronger (odds ratios (ORs): 126 and 39, respectively). After adjusting for EuroScore, volume of intraoperative packed red blood cells, and aortic cross-clamp time, subclinical and combined AKI remained associated with greater in-hospital mortality than no AKI and clinical AKI (adjusted ORs: 28.118, 95% CI 1.465–539.703; 3.737, 95% CI 1.746–7.998). Cox proportional hazard models found a significant association of biomarker-informed AKI subtypes with long-term survival compared with no AKI (adjusted ORs: pooled subclinical and clinical AKI: 1.885, 95% CI 1.003–3.542; combined AKI: 1.792, 95% CI 1.367–2.350). Conclusions In the presence or absence of KDIGO clinical criteria for AKI, the urinary NGAL/hepcidin-25-ratio appears to detect prognostically relevant AKI subtypes. Trial registration number NCT00672334, clinicaltrials.gov, date of registration: 6th May 2008, https://clinicaltrials.gov/ct2/show/NCT00672334. Graphic abstract Definition of AKI subtypes: subclinical AKI (KDIGO negative AND Ratio-positive), clinical AKI (KDIGO positive AND Ratio-negative) and combined AKI (KDIGO positive AND Ratio-positive) with urinary NGAL/hepcidin-25 ratio-positive cut-off at 85% specificity for in-hospital death. AKI, acute kidney injury. AUC, area under the curve. NGAL, neutrophil gelatinase-associated lipocalin. KDIGO, Kidney Disease Improving Global Outcomes Initiative AKI definition.

© 2020 Elsevier Ltd. All rights reserved., Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.

It was shown that hypertension delays SARS CoV-2 viral clearance and exacerbates airway hyperinflammation in the respiratory tract. However, it is unknown whether hypertension determines the long-term cellular and humoral response to SARS Cov2. Health care workers (HCWs) after an outbreak of SARS Cov-2 infections were analyzed. Infected HCWs were not vaccinated before blood collection. 5-14 months (median 7 months) after detection of SARS CoV-2 infection, blood was taken to analyze humoral response (S1 IgG and SARS CoV-2 neutralizing antibodies) and cellular (T cell responses to SARS-CoV-2 with Lymphocyte Transformation Test). To identify clinical factors that determine the immune response, a multivariate regression analysis was done considering age, BMI, sex, diabetes, hypertension, smoking, COPD, asthma and time between PCR positivity and blood collection as confounding factors. Infected hypertensive HCWs more often needed to be hospitalized than non-hypertensive HCWs, but were less likely to develop anosmia and myalgia. The long-term humoral and cellular immune response was significantly strengthened in hypertensive versus normotensive infected HCWs. Multivariate regression analysis revealed that hypertension was independently associated with the humoral response to SARS CoV-2 infection. Multivariate regression analysis using same confounding factors for the humoral response showed a clear trend for an association with the cellular response to SARS CoV-2 infection as well. In conclusion, SARS CoV-2 infection strengthened immune response to SARS CoV-2 infection in hypertensive HCWs independent of other risk factors.

The aim of the study was to investigate whether retinal neurovascular structural impairment in children and adolescents with type 1 diabetes mellitus (T1D) without clinical signs of diabetic retinopathy (DR) could be detected early via optical coherence tomography (OCT) and OCT angiography (OCTA). In the current prospective, cross-sectional, observational clinical study children and adolescents with T1D without DR were evaluated between December 2018 and May 2019. Retinal neurovascular structures in the macular and optic disc regions were examined in detail and quantitatively assessed using OCT and OCTA. Data from subjects with T1D were compared with data from healthy controls. Whether retinal neurovascular structural changes were significantly associated with puberty stage, diabetes duration, and HbA1c level was also investigated. The T1D group included 110 eyes and the control group included 84 eyes. In the T1D group the mean inside disc vessel density (VD) was significantly lower than that of the control group (p

Background Babies born small for gestational age (SGA) are at risk of obesity and metabolic syndrome (MetS). Spexin (SPX) is a novel peptide implicated in food intake and obesity. Spexin levels are lower in obese subjects. This study investigated the potential association of SPX and some obesity related peptides such as leptin and active ghrelin with size at birth and MetS components in prepubertal children born term and either SGA or appropriate for GA (AGA). Secondary aim was to identify whether any of the investigated peptides were associated with MetS components. Methods We conducted a cross-sectional study of 37 consecutive (median age: 5.6 y) SGA- and 50 (median age: 5.9 y) AGA-born children. Clinical evaluations were performed using standard methods. Several biochemical variables (SPX, total leptin, and active ghrelin levels) were analyzed. Age-dependent cut-off values were used to define MetS components, including excess adiposity, hypertension, insulin resistance, and dyslipidemia. The associations between the assessed clinical and laboratory variables and MetS components were investigated. Results Children born SGA had higher frequencies of MetS components than AGA-born peers (p 0.05 for all). Serum SPX levels were lower in children with at least one metS component than those without MetS components (p = 0.018). Conclusions Size at birth had no association with serum SPX. Serum SPX levels are decreased in prepubertal children with MetS components.

BACKGROUND Acute kidney injury requiring renal replacement therapy (AKI-RRT) is strongly associated with mortality after cardiac surgery; however, options for early identification of patients at high risk for AKI-RRT are extremely limited. Early after cardiac surgery, the predictive ability for AKI-RRT even of one of the most extensively evaluated novel urinary biomarkers, neutrophil gelatinase-associated lipocalin (NGAL), appears to be only moderate. We aimed to determine whether the NGAL/hepcidin-25 ratio (urinary concentrations of NGAL divided by that of hepcidin-25) early after surgery may compare favorably to NGAL for identification of high-risk patients after cardiac surgery. METHODS This is a prospective substudy of the BICARBONATE trial, a multicenter parallel-randomized controlled trial comparing perioperative bicarbonate infusion for AKI prevention to usual patient care. At a tertiary referral center, 198 patients at increased kidney risk undergoing cardiac surgery with cardiopulmonary bypass were included into the present study. The primary outcome measure was defined as AKI-RRT. Secondary outcomes were in-hospital mortality and long-term mortality. We compared area under the curve of the receiver operating characteristic (AUC-ROC) of urinary NGAL with that of the urinary NGAL/hepcidin-25 ratio within 60 minutes after end of surgery. We compared adjusted AUC and performed cross-validated reclassification statistics of the (logarithmic) urinary NGAL/hepcidin-25 ratio adjusted to Cleveland risk score/EuroScore, cross-clamp time, age, volume of packed red blood cells, and (logarithmic) urinary NGAL concentration. The association of the NGAL/hepcidin-25 ratio with long-term patient survival was assessed using Cox proportional hazard regression analysis adjusting for EuroScore, aortic cross-clamp time, packed red blood cells and urinary NGAL. RESULTS Patients with AKI-RRT (n = 13) had 13.7-times higher NGAL and 3.3-times lower hepcidin-25 concentrations resulting in 46.9-times higher NGAL/hepcidin-25 ratio early after surgery compared to patients without AKI-RRT. The NGAL/hepcidin-25 ratio had higher AUC-ROC compared with NGAL for risk of AKI-RRT and in-hospital mortality (unadjusted AUC-ROC difference 0.087, 95% confidence interval [CI], 0.036-0.138, P < .001; 0.082, 95% CI, 0.018-0.146, P = .012). For AKI-RRT, the NGAL/hepcidin-25 ratio increased adjusted category-free net reclassification improvement (cfNRI; 0.952, 95% CI, 0.437-1.468; P < .001) and integrated discrimination improvement (IDI; 0.040, 95% CI, 0.008-0.073; P = .016) but not AUC difference. For in-hospital mortality, the ratio improved AUC of the reference model (AUC difference 0.056, 95% CI, 0.003-0.108; P = .037) and cfNRI but not IDI. The urinary NGAL/hepcidin-25 ratio remained significantly associated with long-term mortality after adjusting for the model covariates. CONCLUSIONS The urinary NGAL/hepcidin-25 ratio appears to early identify high-risk patients and outperform NGAL after cardiac surgery. Confirmation of our findings in other cardiac surgery centers is now needed.

Background:Acute rheumatic fever in childhood continues to cause serious morbidity despite all developments. The objective of this study was to evaluate the clinical and laboratory characteristics of patients with acute rheumatic fever and to determine the frequency of subclinical carditis and the side effects of the drugs used in the treatment.Methods:The data of patients hospitalised between 2008 and 2018 with the diagnosis of acute rheumatic fever were included in the study. The relationship of gender and age with the frequency of major symptoms and the distribution of the drugs used in the treatment and their side effects were evaluated.Results:Medical records of 102 patients with complete data were reviewed. 56.9% of the patients were male and the mean age was 10.7 ± 1.9 years. The most common distribution of complaints found were arthritis (51%), arthralgia (25.5%) and fever (16.7%). 10.8% of all patients (n = 11) were diagnosed subclinical carditis via echocardiographic evaluation. The frequency of carditis was higher in female patients with a borderline statistical significance (p = 0.05). However, there was no statistically significant difference between gender and arthritis (p = 0.22) and carditis (p > 0.05). Anti-congestive therapy was required in 22% and inotropic treatment was needed in 6.1% cases. Toxic hepatitis developed in four cases during the acetylsalicylic acid treatment.Conclusions:In a 10-year period, detection of subclinical carditis in 10.8% cases supported that echocardiography should be performed as a standard method for the diagnosis of acute rheumatic fever. Patients should be followed closely in terms of hepatic toxicity due to acetylsalicylic acid used in the treatment.

BACKGROUND Vascular calcification is common in chronic kidney disease and is associated with significant cardiovascular morbidity and mortality. One of the important factors regulating vascular calcification is osteoprotegerin (OPG). There are, however, limited data on the impact of OPG on all-cause mortality and graft loss in kidney transplant recipients so far. Given its impact on vascular calcification, the aim of our study is to analyze whether OPG was a risk factor of all-cause mortality and graft loss in 600 stable kidney transplant recipients. MATERIALS AND METHODS 600 stable renal transplant recipients (367 women, 233 men) were followed for all-cause mortality and graft loss for 3 years. Blood and urine samples for analysis and clinical data were collected at study entry. We performed Kaplan-Meier survival analysis and Cox regression models considering confounding factors such as age, estimated glomerular filtration rate (eGFR), cold ischemia time, HbA1c, phosphorus, calcium, and albumin. RESULTS 65 patients died, and 38 patients had graft loss during the observation period. The OPG baseline concentrations had no effect on graft loss, whereas Kaplan-Meier survival curve showed that baseline plasma OPG concentrations were associated with all-cause mortality in stable kidney transplant recipients (p

Objectives To determine the allergic reactions that develop after Measles and Measles-Mumps-Rubella (MMR) vaccination, and whether any delay in the timing of vaccination occurs in children with food allergy. Methods Children with food allergy who were admitted to the Sisli Hamidiye Etfal Training and Research Hospital Healthy Child Clinic between 1st January 2015 and 30th June 2018 for Measles or MMR vaccination were studied retrospectively. Their age, delayed days of vaccination, the types of allergic food, the results of the specific IgE and skin tests, and any reaction after the vaccination were recorded. Results During the study period, 159 patients were vaccinated and 170 doses of Measles or MMR vaccine were administered. Children allergic to egg were 50.3%, allergic to egg and milk were 25.8%, and 13.2% had multiple food allergy including egg. The rate of post-vaccination reactions in the patients with food allergy was 1.76%. Minor reaction was observed in three patients and no anaphylaxis was seen in any patient. Delayed days of vaccination in the patients referred by another center were greater than followed-up by present clinic (p < 0.001). Conclusions Any serious allergic reaction was not observed in this study. Food allergy does not necessitate modification of routine vaccination. Anaphylaxis may develop in any vaccinated child regardless of whether he/she has food allergy or not. Therefore, vaccines should be administered in a healthcare facility that can treat anaphylaxis. WOS:000487126700012 31104294 Q3

No-reflow (NR) is one of the major complications of primary percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation myocardial infarction (NSTEMI). We aim to assess the value of multilayer longitudinal strain parameter to predict NR in patients with NSTEMI and preserved ejection fraction. 230 consecutive patients who were admitted to the emergency department and diagnosed with NSTEMI were prospectively included in this study. Echocardiography was performed 1 h before angiography. Specific analysis for endocardial, mid-myocardial and epicardial layers were performed by two-dimensional (2D) speckle tracking echocardiography (STE) for multilayer longitudinal strain. NR was described as flow grade of ≤ TIMI 2 when mechanical occlusions like dissection, intimal tear, arterial spasm and thromboembolism during angiography were excluded. 49 of 168 patients admitted to the study had NR. No significant differences were observed between the groups regarding age and gender. Multilayer longitudinal strain imaging (endocard, midmyocard and epicard) revealed lower strain values particularly in endocardial layer in patients with NR (GLS-endocard: − 14.14 ± 1.39/− 17.41 ± 2.34, p

Summary: Inferior vena cava syndrome (IVCS) is caused by agenesis, compression, invasion, or thrombosis of the IVC, or may be associated with Budd-Chiari syndrome. Its incidence and prevalence are unknown. Benign IVCS is separated from malignant IVCS. Both cover a wide clinical spectrum reaching from asymptomatic to highly symptomatic cases correlated to the underlying cause, the acuity, the extent of the venous obstruction, and the recruitment and development of venous collateral circuits. Imaging is necessary to determine the underlying cause of IVCS and to guide clinical decisions. Interventional therapy has changed the therapeutic approach in symptomatic patients. This article provides an overview over IVCS and focuses on interventional therapeutic methods and results.

25-Hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)2D) need to be bound to carrier proteins to be transported to their target cells. The majority of either 25OHD or 1,25(OH)2D is bound to vitamin D-binding protein (DBP), a smaller fraction is bound to albumin and only very small amounts of 25OHD or 1,25(OH)2D are free. Albumin-bound 25OHD or 1,25(OH)2D is relatively easily available after dissociation from albumin. Thus, the sum of free and albumin-bound forms is called bioavailable 25OHD and bioavailable 1,25(OH)2D. Total 25OHD and 1,25(OH)2D are defined as the sum of free, albumin-bound and DBP-bound 25OHD and 1,25(OH)2D, respectively. This cross-sectional study in 427 pregnant women compared the correlation of the six vitamin D compounds with biomarkers of bone health, lipid metabolism, kidney function, endocrine parameters, and group B water-soluble vitamins. Among the 25OHD metabolites analysed, total 1,25(OH)2D showed clearly the best correlation with calcium, bone-specific alkaline phosphatase, adiponectin, LDL, HDL, urea, thyroxine, and group B water-soluble vitamins. When comparing the three 25OHD metabolites, both free 25OHD and bioavailable 25OHD showed overall good correlations with calcium, bone-specific alkaline phosphatase, adiponectin, LDL, HDL, urea, thyroxine, triiodothyronine, and group B water-soluble vitamins, The correlations of 1,25(OH)2D and 25OHD metabolites went always in opposite directions. Only PTH correlates always inversely with all six vitamin D compounds. In conclusion, free 25(OH)D and bioavailable 25(OH)D are more precise determinants of the vitamin D status than total 25(OH)D in normal pregnancy, whereas total 1,25(OH)2D is superior to free and bioavailable 1,25(OH)2D. Except for PTH, correlations of 25(OH)D and 1,25(OH)2D metabolites with typical clinical chemistry readouts go in opposite directions.

BackgroundIncreased fibroblast growth factor 23 (FGF23) is a risk factor for mortality, cardiovascular disease, and progression of chronic kidney disease. Limited data exist comparing the association of either c-terminal FGF23 (cFGF23) or intact FGF23 (iFGF23) in kidney transplant recipients (KTRs) with overall (all-cause) graft loss.MethodsWe conducted a prospective observational cohort study in 562 stable kidney transplant recipients. Patients were followed for graft loss and all-cause mortality for a median follow-up of 48 months.ResultsDuring a median follow-up of 48 months, 94 patients had overall graft loss (primary graft loss or death with functioning graft). Both cFGF23 and iFGF23 concentrations were significantly higher in patients with overall graft loss than those without (24.59 [11.43–87.82] versus 10.67 [5.99–22.73] pg/ml;p p = 0.002 for cFGF23 and iFGF23, respectively). Time-dependent ROC analysis showed that cFGF23 concentrations had a better discriminatory ability than iFGF23 concentrations in predicting overall (all-cause) graft loss. Cox regression analyses adjusted for risk factors showed that cFGF23 (HR for one unit increase of log transformed cFGF23: 1.35; 95% CI, 1.01–1.79;p = 0.043) but not iFGF23 (HR for one unit increase of log transformed iFGF23: 0.97; 95% CI, 0.75–1.25;p = 0.794) was associated with the overall graft loss.ConclusionElevated cFGF23 concentrations at baseline are independently associated with an increased risk of overall graft loss. iFGF23 measurements were not independently associated with overall graft loss. The cFGF23 ELISA might detect bioactive FGF23 fragments that are not detected by the iFGF23 ELISA.

Summary: The superior vena cava syndrome (SVCS) is caused by compression, invasion, and/or thrombosis of the superior vena cava and/or the brachiocephalic veins. Benign SVCS is separated from malignant SVCS. SVCS comprises a broad clinical spectrum reaching from asymptomatic cases to rare life-threatening emergencies with upper airway obstruction and increased intracranial pressure. Symptoms are correlated to the acuity and extent of the venous obstruction and inversely correlated to the development of the venous collateral circuits. Imaging is necessary to determine the exact underlying cause and to guide further interventions. Interventional therapy has widely changed the therapeutic approach in symptomatic patients. This article provides an overview over this complex syndrome and focuses on interventional therapeutic methods and results.

Background T‐wave peak‐to‐end interval (TPEI) is a measure of repolarization dispersion on surface electrocardiogram (ECG). TPEI has been reported as a prognostic parameter with heart disorders. In this study, we aimed to evaluate the relationship between echocardiogram‐derived right heart parameters, right heart catheterization (RHC) measurements, and TPEI in patients with precapillary pulmonary arterial hypertension (PAH). Methods Thirty‐eight patients (29 females and 9 males, mean age of 54.9 ± 10.9 years) who had undergone RHC for a preliminary diagnosis of pulmonary hypertension (PH) were included in the study. We performed transthoracic echocardiography (TTE), and resting 12‐lead ECG was recorded before RHC. TPEI was measured from leads of V1‐V6, DII, DIII, and aVF, and these values are averaged to obtain the global TPEI. Results Duration of TPEI was significantly correlated with mean PAP, pulmonary vascular resistance (PVR), and cardiac index (CI). Longer TPEI was associated with higher N terminal probrain natriuretic peptide (NT pro‐BNP) level, lower 6‐min walk distance (6MWD), and lower tricuspid annular plane systolic excursion (TAPSE). Conclusion Prolongation of TPEI could be a new predictor of adverse outcome in PAH and may provide additional prognostic information for patients with PAH.

Addressing early childhood development (ECD) and developmental difficulties (DDs) in low and middle-income countries (LMICs) requires applicable and sustainable programs. Seven years after its implementation in 2010, we evaluated the Developmental Pediatrics Unit (DPU) Training Program in pediatric referral centers in Turkey.We applied crosssectional design and quantitative/qualitative methods to assess services, training, research and advocacy of the DPUs.Five of six established DPUs sustained clinical services, training, research, and advocacy. A total of 23,710 children (9085 new cases in 2017) had been referred mainly for perinatal risks and chronic illness, all centers contributed with similar proportions of children. Staff motivation and endurance, hospital administrator support, and client satisfaction facilitated the program; whereas invisibility within the performance based healthcare system was a barrier.In Turkey and possibly other LMICs, the DPU Training Program is applicable and sustainable if health system barriers are addressed.Introducción. El abordaje del desarrollo en la primera infancia (DPI) y las dificultades del desarrollo (DD) en los países de ingresos bajos o medios (PIBM) requiere de programas aplicables y sostenibles. Se evaluó el programa de capacitación para las unidades de pediatría del desarrollo (UPD) en los centros de referencia tras siete años. Población y métodos. Diseño transversal con métodos cualicuantitativos para evaluar los servicios, la capacitación, la investigación y la promoción de las UPD. Resultados. Se mantuvieron los servicios clínicos, la capacitación, investigación y promoción. En total, 23 710niños fueron derivados. La motivación y resistencia del personal, el respaldo de los administradores y la satisfacción del paciente facilitaron el programa, aunque la invisibilidad dentro del sistema de salud fue un obstáculo. Conclusiones. En Turquía, y posiblemente otros PIBM, el programa de capacitación para las UPD es aplicable y sostenible si se abordan los obstáculos del sistema de salud.

Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare but life-threatening condition. In 2018, the nanobody caplacizumab was approved for the treatment of adults experiencing an acute episode of aTTP, in conjunction with plasma exchange (PEX) and immunosuppression for a minimum of 30 days after stopping daily PEX. We performed a retrospective, observational analysis on the use of caplacizumab in 60 patients from 29 medical centers in Germany during acute disease management. Caplacizumab led to a rapid normalization of the platelet count (median, 3 days; mean 3.78 days). One patient died after late treatment initiation due to aTTP-associated complications. In 2 patients with initial disease presentation and in 4 additional patients with laboratory signs of an exacerbation or relapse after the initial therapy, PEX-free treatment regimens could be established with overall favorable outcome. Caplacizumab is efficacious in the treatment of aTTP independent of timing and ancillary treatment modalities. Based on this real-world experience and published literature, we propose to administer caplacizumab immediately to all patients with an acute episode of aTTP. Treatment decisions regarding the use of PEX should be based on the severity of the clinical presentation and known risk factors. PEX might be dispensable in some patients.

Introduction of the nanobody caplacizumab was shown to be effective in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP) in the acute setting. The official recommendations include plasma exchange (PEX), immunosuppression, and the use of caplacizumab for a minimum of 30 days after stopping daily PEX. This study was a retrospective, observational analysis of the use of caplacizumab in 60 patients from 29 medical centers in Germany. Immunosuppressive treatment led to a rapid normalization of ADAMTS13 activities (calculated median, 21 days). In 35 of 60 patients, ADAMTS13 activities started to normalize before day 30 after PEX; in 11 of 60 patients, the treatment was extended beyond day 30; and in 5 patients, it was extended even beyond day 58 due to persistent autoimmune activity. In 34 of 60 instances, caplacizumab was stopped before day 30 with a favorable outcome whenever ADAMTS13 activities were >10%. In contrast, 11 of 34 patients with ADAMTS13 activities

BACKGROUND Adolescent pregnancy remains a global public health issue with serious implications on maternal and child health, particularly in developing countries The aim of this study was to investigate maternal characteristics and obstetric and neonatal outcomes of singleton pregnancies among adolescents. MATERIAL AND METHODS A total of 241 adolescent women who gave birth to singletons between January 2015 and December 2015 at our hospital were included in this descriptive cross-sectional study. Data on maternal sociodemographic and obstetric characteristics as well as neonatal outcome were recorded. RESULTS Primary school education (66.0%), lack of regular antenatal care (69.7%), religious (36.7%) and consanguineous (37.0) marriage, Southeastern Anatolia hometown (34.9%) and Eastern Anatolia hometown (21.2%) were noted in most of the adolescent pregnancies, while 95% were desired pregnancies within marriage. Pregnancy complications were noted in 19.5% (preeclampsia in 5.8%) and cesarean delivery was performed in 44.8% of adolescent pregnancies. Preterm delivery rate was 27.0% (20.3% were in >34 weeks). Overall, 13.3% of neonates were admitted to neonatal intensive care unit (NICU) in the postpartum period (prematurity in 28.1%), while 25.3% were re-admitted to NICU admission in the post-discharge 1-month (hyperbilirubinemia in 55.7%). Adolescent pregnancies were associated considerably high rates of fetal distress at birth (28.7%), preterm delivery (26.9%), and re-admission to NICU after hospital discharge (25.3%). CONCLUSIONS In conclusion, our findings indicate that along with considerably high rates of poor antenatal care, maternal anemia and cesarean delivery, adolescent pregnancies were also associated with high rates for fetal distress at birth, preterm delivery, and NICU re-admission within post-discharge 1-month.

Introduction: The aim of this study was to determine the knowledge, attitudes, and practices of family physicians and pediatricians in regard to adolescent immunization. Methods: The study was conducted from March to May 2017. A total of 665 physicians participated. Participants were asked 31 questions about their personal sociodemographic characteristics and their knowledge, attitudes, and practices around adolescent immunization. Results: The study sample consisted of 348 family physicians (52.3% of the sample) and 317 pediatricians (47.7%). The results showed that 5.4% of family physicians and 10.4% of pediatricians thought that they had enough knowledge about adolescent immunization (p

BACKGROUND: In patients with acute kidney injury (AKI), specialized treatment—initiated in response to an early-warning system—may be beneficial compared with routine treatment. METHOD: To explore effect estimators in a pilot trial (DRKS00010530), patients with AKI on regular wards of a university hospital were treated either in the usual way (control group) or more intensively (intervention group). The subjects were allotted randomly to the two treatment groups. The more intensive treatment consisted of an early warning system for a rise in the serum creatinine concentration, immediate consultation of a specialist, and the issuance of a patient kidney passport. The primary endpoint was recovery of renal function after AKI during the index hospitalization. Renal complications and process indicators were the secondary endpoints. RESULTS: The proportion of patients whose renal function returned to baseline after AKI was 50% in the intervention group (N = 26) and 42% in the control group (N = 26) (odds ratio 1.4, 95% confidence interval [0.5; 4.0], p = 0.58). The calculated glomerular filtration rate went down, from hospital admission to discharge, by 3 mL/min/1.73 m(2) (1st–3rd quartile: [6; –20]) in the intervention group and by 13 mL/min/1.73 m(2) in the control group (1st–3rd quartile: [0; –25]; p = 0.09). Complications of AKI such as hyperkalemia, pulmonary edema, and renal acidosis were rarer in the intervention group (15% versus 39%; p = 0.03). In the intervention group, compared with the control group, the cause of AKI was identified more frequently (27% versus 4%; p = 0.05); drugs with relevance to the kidney were discontinued more frequently (65% versus 31%; p = 0.01); and the diagnosis of AKI was more frequently documented in the patient’s chart (58% versus 37%; p = 0.03). CONCLUSION: Specialized consultations supported by an early warning system for AKI seem to be beneficial for patients. The findings of this pilot trial should be verified in larger-scale randomized controlled trials.

Objectives. To assess and evaluate the risk factors affecting the neuromotor development of preterm babies at corrected age 18 to 24 months. Methods. Preterm babies ≤ 34 weeks of gestational age (GA) who were born in our hospital between 2011 and 2014 were prospectively included in the study. Prenatal, perinatal, and postnatal features of the babies were recorded. Bayley Scales of Infants and Toddler Development, Third Edition (Bayley-III), was applied at corrected age 18 to 24 months. Results. All data of 96 babies were obtained during the study, mean birth weight was 1542 ± 518 g, and mean corrected age was 20.9 ± 4.7 months. Cerebral palsy was found in 11 babies (11.5%). According to Bayley III scores, 13.5% cognitive delay, 19.8% language delay, and 33.3% motor delay rations were detected. A positive correlation was found between GA and motor composite scores ( p = 0.011 ). The mean motor composite score was lower in babies with the Apgar score less than 7 at 1st and 5th minutes ( p = 0.007 and p = 0.003 ) and applied resuscitation in the delivery room ( p = 0.033 ). The mean language composite score was found to be higher in babies with antenatal steroid administration ( p = 0.003 ). A negative correlation was found between the motor composite score and the oxygen treatment time and mechanical ventilation support time ( p = 0.001 and p = 0.007 ). Conclusion. In preterm babies less than 34 weeks, the birth weight, GA, Apgar score, oxygen treatment time, mechanical ventilation support time, and resuscitation in a delivery room were determined to affect the Bayley III motor score. Language development was found better in babies with antenatal steroid administration.

The randomized, controlled STOP-IgAN trial in patients with IgA nephropathy (IgAN) and substantial proteinuria showed no benefit of immunosuppression added on top of supportive care on renal function over three years. As a follow-up we evaluated renal outcomes in patients over a follow-up of up to ten years in terms of serum creatinine, proteinuria, end-stage kidney disease (ESKD), and death. The adapted primary endpoint was the time to first occurrence of a composite of death, ESKD, or a decline of over 40% in the estimated glomerular filtration rate (eGFR) compared to baseline at randomization into STOP-IgAN. Data were analyzed by Cox-regression models. Follow-up data were available for 149 participants, representing 92% of the patients originally randomized. Median follow-up was 7.4 years (inter quartile range 5.7 to 8.3 years). The primary endpoint was reached in 36 of 72 patients randomized to supportive care and 35 of 77 patients randomized to additional immunosuppression (hazard ratio 1.20; 95% confidence interval 0.75 to 1.92). ESKD occurred in 17 of the patients with supportive care and in 20 of the patients with additional immunosuppression. Additionally, the rates of eGFR loss over 40% and annual eGFR loss did not differ between groups. Two patients died with supportive care and three with additional immunosuppression. Thus, within the limitations of a retrospective study, over a follow-up of up to ten years, and using an adapted primary endpoint, we failed to detect differences in key clinical outcomes in IgAN patients randomized to receive added immunosuppression on top of supportive care versus supportive care alone.

Background: Endostatin is a 20-kDa C-terminal fragment of collagen XVIII, known for its ability to inhibit the proliferation of capillary endothelial cells. Previous studies suggested that circulating endostatin independently predicts incident chronic kidney disease. However, the impact of endostatin on graft loss level in kidney transplant recipients (KTRs) remains unknown. Methods: We conducted a prospective observational cohort study in 574 maintenance KTRs. Patients were followed for kidney graft loss and all-cause mortality during a median follow-up of 48 months. Serum-, and urine-samples and clinical data were collected at baseline. Serum Endostatin concentration was analyzed by an ELISA. Results: Among 574 patients, 37 patients had graft loss and 62 patients died. For graft loss, the optimal cut-off value based on receiver operating characteristics analysis (area under the curve 0.79, 95% CI 0.71–0.86, p < 0.001) of endostatin was 147.3 pmol/L. Kaplan-Meier curves revealed that higher serum endostatin concentrations positively correlated with graft loss (p < 0.001). Multivariable Cox regression analyses showed that baseline endostatin concentrations were significantly associated with graft loss after adjusting for graft loss risk factors (adjusted hazard ratio [HR] 8.34; 95% CI 2.19–31.72; p = 0.002). The adjusted HRs for classical graft loss risk factors such as baseline estimated glomerular filtration rate and urinary protein excretion were lower (1.91 and 5.44, respectively). In contrast to graft loss, baseline endostatin concentrations were not associated with all-cause mortality. Conclusion: Increased serum endostatin at baseline is independently associated with the risk of graft loss in KTRs.

Maternal smoking during pregnancy affects fetal neurological development. Metabolomic studies in the general population suggest that smoking is associated with characteristic metabolic alterations. We investigated the association between the maternal smoking status, the fetal metabolome and head circumference at birth, as a surrogate parameter of brain development. 320 mother/newborn pairs of the Berlin Birth Cohort were investigated. Anthropometric parameters, including head circumference, of newborns of smoking mothers, former smoking mothers, and never smoking mothers were compared to assess the impact of maternal smoking behavior. Associations between maternal smoking behavior and 163 cord blood metabolites and associations between newborn head circumference and concentrations of smoking behavior related metabolites were analysed. Male newborns of smoking mothers had a reduced head circumference when compared with newborns from former smoking and never smoking mothers (p < 0.05). Using linear regression models corrected for established confounding factors, maternal smoking during pregnancy showed an independent association with head circumference (95% CI: -0.75～-0.41 cm, p = 2.45×10-11). In a stepwise linear regression model corrected for known confounding factors of brain growth lyso-phosphatidylcholine 20:3 (95% CI: 6.68～39.88 cm, p = 4.62×10-4) was associated with head circumference in male offspring only. None of the metabolites were associated with head circumference of female newborns. In conclusion, maternal smoking during pregnancy impacted on male offspring's development including brain development. The smoking related metabolite lyso-phosphatidylcholine 20:3 was associated with head circumference of male offspring.

The aim of this study was to evaluate vitamin D levels between 12-24 monthold healthy children supplemented with vitamin D (400 IU/day) during the first year.Descriptive-sectional study conducted between June 2015, and May 2016, in Istanbul (latitude 41ºN). Children aged 12-24 months followed up by the well-child clinic who had vitamin D supplementation in the first year were included in the study. The levels of calcium, phosphorus, alkaline phosphatase, parathyroid hormone and 25-hydroxyvitamin D [25(OH)D] were measured. Vitamin D status was defined as20 ng/mL: sufficiency, 15-20 ng/mL: insufficiency and15 ng/mL: deficiency.The study was completed with 197 children. 26.9 % of children (n = 53) went on receiving supplementation after one year (mean dose 491 ± 267 IU/day). The mean 25(OH)D level was 38.0 ± 13.9 ng/mL. It was found that regular vitamin D intake under one year of age (p = 0.008) and continued support after one year of age (p = 0.042) increased level of 25(OH)D in children aged 12-24 months. Vitamin D deficiency was found in 4.1 % and vitamin D insufficiency in 7.1 %. Mother's education (p = 0.009) and use of formula (p = 0.012) were protective factors in relation to development of vitamin D deficiency or insufficiency.The level of 25(OH)D was sufficient in 88.8 % of children aged 12-24 months receiving 400 IU/day vitamin D supplementation in the first year. Vitamin D supplementation could not be required in healthy children aged 12- 24 months who received properly vitamin D supplementation in the first year.Introducción. El objetivo fue evaluar la concentración de vitamina D en niños sanos de 12 a 24 meses suplementados con vitamina D (400 UI/día) durante el primer año. Métodos. Estudio descriptivo transversal entre junio de 2015 y mayo de 2016 en Estambul. Se incluyó a niños de 12 a 24 meses en seguimiento en la clínica del niño sano y con suplementación con vitamina D durante el primer año. Se midió calcio, fósforo, fosfatasa alcalina, hormona paratiroidea y 25-hidroxivitamina D [25(OH)D]. Se definió suficiencia (20 ng/ml), insuficiencia (15-20 ng/ ml) y deficiencia (15 ng/ml) de vitamina D. Resultados. El estudio incluyó 197 niños. El 26,9 % (n = 53) siguió recibiendo suplementación después del año (dosis media: 491 ± 267 UI/ día). La concentración media de 25(OH)D fue 38,0 ± 13,9 ng/ml. La ingesta regular de vitamina D en menores de un año (p = 0,008) y la continuación de suplementación después del año (p = 0,042) aumentaron la concentración de 25(OH)D en niños de 12 a 24 meses. Hubo deficiencia en 4,1 % e insuficiencia en 7,1 %. El nivel educativo materno (p = 0,009) y la leche maternizada (p = 0,012) fueron factores protectores contra deficiencia o insuficiencia. Conclusiones. La concentración de 25(OH)D era suficiente en el 88,8 % de los niños de 12 a 24 meses con suplementación con vitamina D (400 UI/día) durante el primer año. Los niños sanos de 12 a 24 meses con una suplementación correcta de vitamina D en el primer año podrían no requerir suplementación.

Free vitamin D is the biologically active form of vitamin D. Vitamin D deficiency is associated with cardiovascular disease, the most common cause of mortality in hemodialysis patients. The goal of our current study was to investigate the relation between blood concentrations of free 25-hydroxyvitamin D with cardiovascular events in end-stage chronic kidney disease patients on hemodialysis, because this is unknown so far. We measured free vitamin D levels in 117 stable consecutive prevalent patients in September as a surrogate of vitamin D exposure during the past 6 months, and recorded the number of cardiovascular events during the previous 6 months defined as hospitalization due to heart failure, episodes of acute coronary syndrome, and stroke. Fourteen events occurred during the observation period. In patients without any cardiovascular events the free vitamin D levels were significantly higher as compared to those with cardiovascular events (patients without events: 5.68 [4.37–9.27] pg/mL; patients with events: 4.74 [3.46–5.37] pg/mL, p = 0.015). This finding remained stable after multiple regression analysis considering confounding factors such as age, time on dialysis, preexisting diabetes, hypertension, and coronary heart disease. In conclusion, our study shows that free vitamin D serum concentrations are independently associated with major cardiovascular events in chronic kidney disease patients on dialysis.

Endothelial specific molecule 1 (Endocan) is a biomarker of the inflammatory process occurring in endothelial cells. It was shown that endocan was increased in acute coronary syndromes. We aimed at investigating the endocan levels in acute coronary syndrome patients after coronary bypass surgery.The study included 35 patients who presented with acute coronary syndrome to the Emergency Department. Serum endocan levels and other inflammatory markers were evaluated before and after coronary artery by-pass surgery. The correlation coefficients and their significance were calculated by Pearson's test and the difference in mean values before and after bypass surgery was calculated by paired sample t-test. Statistical analyses were performed using SPSS version 20.0 (SPSS Inc., Chicago, IL, USA). Statistical significance was taken as p0.05.There was a significant change in serum hs-CRP and endocan levels and also LVEF before and after CABG operation (p0.05).Serum endocan level was significantly decreased after successful reperfusion in our study. Thus, it may be an important biomarker in terms of clinical use as an indicator of successful reperfusion.

INTRODUCTION Two-dimensional (2D) speckle-tracking echocardiographic (STE) imaging is frequently performed in the assessment of cardiovascular diseases. We aim to investigate the role of the global and territorial longitudinal strain (GLS and TLS) values assessed via 2D STE imaging to detect significant coronary artery disease (CAD) in non-ST-segment elevation myocardial infarction (NSTEMI) patients without wall-motion abnormalities. METHODS This study enrolled 150 patients with the diagnosis of NSTEMI. Patients who had typical chest pain with unstable angina characteristics within the last 24 hours were 18-80 years of age and had a typical rise and/or fall of cardiac biomarkers were included. Myocardial functions were assessed via myocardial deformation analyses of 2D STE images. RESULTS The mean age of the CAD group was 52.91 ± 9.11, vs 50.31 ± 8.32 in the control group. In the CAD group, 56 patients were male (65%), whereas 21 were male (60%) in control group. GLS and TLS assessments demonstrated a statistically significant difference between CAD and control groups, with GLS values of -16.27 ± 1.91 and -18.74 ± 1.93 (P

Patients with primary aldosteronism induced hypertension are more likely to experience cardiovascular events compared to patients with essential hypertension. Primary aldosteronism may therefore have distinct adverse effects on cardiovascular structure and function, independent of hypertension. However, current data on such effects of primary aldosteronism are conflicting. The aim of the present study was to investigate the influence of primary aldosteronism on vascular structure and endothelial function, using intima-media thickness as a vascular remodeling index and flow-mediated dilation as a functional parameter. In total, 70 participants were recruited from patients with resistant hypertension. Twenty-nine patients diagnosed with primary aldosteronism and 41 patients with essential hypertension were prospectively enrolled. Primary aldosteronism was due to aldosterone-producing adenoma in 10 cases and due to idiopathic adrenal hyperplasia in 19 cases. All patients underwent ultrasound of the common carotid intima-media thickness and flow-mediated dilation of the brachial artery. Primary aldosteronism patients had significantly lower flow-mediated dilation (3.3 [2.4-7.4] % vs 14.7 [10.3-19.9] %, P 0.05). Hypertensive patients with hyperaldosteronism appear to exhibit deteriorative effects on both vascular structure and function, independent of hypertension.

A 31-year-old male patient presented with complaints of palpitations, dizziness, and recurrent episodes of syncope. A 12-lead electrocardiogram (ECG) revealed manifest ventricular preexcitation, which suggested Wolff Parkinson White syndrome. In addition, an incomplete right bundle branch block and a 3-mm ST segment elevation ending with inverted T-waves in V2 were consistent with coved-type (type 1) Brugada pattern. An electrophysiological study was performed, and during the mapping, the earliest ventricular activation with the shortest A-V interval was found on the mitral annulus posterolateral site. After successful radiofrequency catheter ablation of the accessory pathway, the Brugada pattern on the ECG changed, which prompted an ajmaline provocation test. A type 1 Brugada ECG pattern occurred following the administration of ajmaline. Considering the probable symptom combinations of these 2 coexisting syndromes and the presence of recurrent episodes of syncope, programmed ventricular stimulation was performed and subsequently, ventricular fibrillation was induced. An implantable cardioverter-defibrillator was implanted soon after.

Objective Energy drinks (EDs) are widely consumed products of the beverage industry and are often chosen by teenagers and young adults. Several adverse cardiovascular events and malignant cardiac arrhythmias following consumption of EDs have been reported in the literature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the dispersion of repolarization and that an increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. This study investigated the acute effects of Red Bull ED on ventricular repolarization as assessed by the Tp-e interval and Tp-e/QT ratio. Methods A prospective, open-label study design was used. After an 8-h fast, 50 young, healthy subjects consumed 355 mL of Red Bull ED. The Tp-e interval, Tp-e/QTc ratio, and several other electrocardiographic parameters were measured at baseline and 2 h after ingestion of Red Bull ED. Results No significant changes in the Tp-e interval or Tp-e/QTc ratio were observed with Red Bull ED consumption. Red Bull ED consumption led to increases in both systolic and diastolic blood pressures, which were associated with an increased heart rate. Conclusion Although ingestion of Red Bull ED increases the heart rate and diastolic and systolic blood pressures, it does not cause alterations in ventricular repolarization as assessed by the Tp-e interval and Tp-e/QTc ratio.

A 51-year-old male patient presented with frequent and symptomatic premature ventricular complexes (PVCs) that had induced cardiomyopathy. Radiofrequency (RF) catheter ablation of the origin of the PVCs was planned and the patient underwent electrophysiological study. During activation mapping, the earliest ventricular activation was identified at the His bundle region. Small His bundle electrogram recording by the distal ablation electrode during sinus rhythm revealed that the earliest ventricular activation during PVC preceded the QRS onset by 58 milliseconds. The PVCs were successfully eliminated without occurrence of atrioventricular block using incremental application of RF energy to the para-Hisian region. At the conclusion of a 5-month follow-up period, the patient remained asymptomatic and transthoracic echocardiography demonstrated an improvement in left ventricular ejection fraction.

Background Arrhythmogenic right ventricular dysplasia (ARVD) is a heritable disorder characterized by fibro-fatty replacement of right ventricular myocytes, increased risk of ventricular arrhythmias, and sudden cardiac death. Galectin-3 (GAL3) is known to play an important role in a number of fibrotic conditions, including cardiac fibrosis. Many studies have focused on the association between GAL3 levels and cardiac fibrosis in heart failure. However, the role of GAL3 in the pathogenesis of ARVD and ventricular arrhythmias has not yet been evaluated thoroughly. The aim of this study was to explore GAL3 levels in patients with ARVD and its association with ventricular arrhythmias. Methods Twenty-nine patients with ARVD and 24 controls were included. All patients with ARVD had an implantable cardiac defibrillator (ICD) for primary or secondary prevention. Ventricular arrhythmia history was obtained from a chart review and ICD data interrogation. Galectin-3 levels were measured using an enzyme-linked immunosorbent assay. Results Patients with ARVD had higher plasma GAL3 levels (16.9 ± 2.6 ng/mL vs 11.3 ± 1.8 ng/mL, P 0.001) than the control group. Ten patients had sustained or non-sustained ventricular arrhythmias during follow-up. In the multivariable analysis, left ventricular disease involvement (HR: 1.05; 95% CI: [1.01-1.12]; P = 0.03); functional capacity2 (HR: 1.21; 95% CI: [1.13-1.31]; P 0.005); and GAL3 levels (HR: 1.05; 95% CI: [1.00-1.11]; P = 0.01) independently predicted VT/VF. Conclusion We demonstrated that serum GAL3 was significantly elevated in patients with ARVD. Also, serum GAL 3 levels could be regarded as a candidate biomarker in the diagnosis of ARVD which needs to be tested in larger prospective studies. In addition, GAL3 levels were higher in patients with VT/VF as compared with those without VT/VF.

Background We aimed to determine the knowledge and attitudes of Turkish pediatricians concerning vitamin D supplement. Methods The study was planned cross-sectional to be carried out between April–May 2015 in Turkey. A questionnaire form that determined the participants’ opinions and practices concerning vitamin D supplement was completed via face-to-face interview. Results A total of 107 pediatricians (49.3%) and 110 pediatric residents (50.7%) participated in the study. Of the physicians, 85.2% recommended vitamin D supplement for all infants and children regardless of diet, 13.4% recommended for the infants which are solely breastfed. Vitamin D supplement is recommended at a dose of 400 IU/day by 88.8% of pediatricians and by 90% of pediatric residents. Of the pediatricians and pediatric residents, 72% and 68.2%, respectively commence vitamin D supplement when the newborn is 15 days old. The rates of recommending vitamin D supplement until the age of one and two years were higher among pediatricians (48.6% and 41.1%, respectively) than pediatric residents (40.9% and 32.7%, respectively). The rate of starting vitamin D supplement for fontanelle closure was significantly higher among pediatric residents (15.5%) than pediatricians (3.7%) (p = 0.002). It was determined that the rate of prescribing vitamin D supplement until fontanelle closure was higher among pediatric residents (18.2%) than pediatricians (0.9%). Conclusions The present study suggest that the knowledge of pediatricians about recommendation of vitamin D needs to be enhanced by education programs in addition to free vitamin D supplement provided by the Ministry of Health.

Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a sensitive and specific diagnostic test for acute kidney injury (AKI) in the Emergency Department (ED), but its economic impact has not been investigated. We hypothesized that uNGAL used in combination with serum creatinine (sCr) would reduce costs in the management of AKI in patients presenting to the ED in comparison to using sCr alone.A cost simulation model was developed for clinical algorithms to diagnose AKI based on sCr alone vs. uNGAL plus sCr (uNGAL+sCr). A cost minimization analysis was performed to determine total expected costs for patients with AKI. uNGAL test characteristics were validated with eight-hundred forty-nine patients with sCr ≥1.5 from a completed study of 1635 patients recruited from EDs at two U.S. hospitals from 2007-8. Biomarker test, AKI work-up, and diagnostic imaging costs were incorporated.For a hypothetical cohort of 10,000 patients, the model predicted that the expected costs were $900 per patient (pp) in the sCr arm and $950 in the uNGAL+sCr arm. uNGAL+sCr resulted in 1,578 fewer patients with delayed diagnosis and treatment than sCr alone (2,013 vs. 436 pts) at center 1 and 1,973 fewer patients with delayed diagnosis and treatment than sCr alone at center 2 (2,227 vs. 254 patients). Although initial evaluation costs at each center were $50 pp higher in with uNGAL+sCr, total costs declined by $408 pp at Center 1 and by $522 pp at Center 2 due to expected reduced delays in diagnosis and treatment. Sensitivity analyses confirmed savings with uNGAL + sCr for a range of cost inputs.Using uNGAL with sCr as a clinical diagnostic test for AKI may improve patient management and reduce expected costs. Any cost savings would likely result from avoiding delays in diagnosis and treatment and from avoidance of unnecessary testing in patients given a false positive AKI diagnosis by use of sCr alone.

Background: The use of antracycline (ANT) in breast cancer has been associated with adverse cardiac events. Two-dimensional (2D) strain imaging (SI) can provide a more sensitive measure of altered left ventricular (LV) systolic function. We aimed to evaluate the preventive effect of carvedilol administration assessed by SI in a patient with breast cancer treated with ANT. Methods: Patients receiving ANT were randomly assigned to the carvedilol- or placebo-receiving group. Each received an echocardiographic examination with conventional 2D echocardiography, pulsed tissue Doppler, and 2D SI prior to and 6 months post ANT treatment. Results: During the 6-month follow-up period there were no patient deaths or interrupted chemotherapy treatments due to doxorubicin-induced cardiotoxicity. Both left ventricular ejection fraction (LVEF) and fractional shortening (FS) were within normal limits for all patients before and after ANT therapy. EF, FS and LV dimensions were measured using M-mode echocardiography and found to be similar in both groups before and after ANT therapy. The mean EF, FS, and LV echocardiograph baseline and control dimensions were similar in both groups after 6 months. Though baseline SI parameters were similar between the groups, there was a significant decrease in LV basal septal and basal lateral peak systolic strain in the control group compared to the carvedilol group. Conclusions: These results indicate that carvedilol has a protective effect against the cardiotoxicity induced by ANT.

Immunhistopathological and serological data favors an immunopathogenesis of thromboangiitis onliterans (TAO, Buerger's disease). Auto antbodies seem to play a major role. Immunoadsorption (IA) proved to be therapeutically effective. We focused on agonistic autoantibodies (agAAB) directed against G-protein coupled receptors (GPCR) and proved the hypothesis, that these agAAB might be present in TAO and that a five day course of IA might be able to eliminate these agAAB effectively.Between December 2012 and May 2014 11 TAO-patients were treated by IA in a five day course. AgAAB-analysis was performed using specific ELISA techniques.AgAAB were detected in 9 out of 11 patients (81.8 %).Multiple agAAB were present in 7 patients (63.6 %). A clustering of agAAB directed against loop1 of the adrenergic α1-receptor and the endothelin-A-(ETA)receptor was identified, representing 72.7 % resp. 54.5 % of the patients. AgAAB directed against the angiotensin-1 (AT-1) epitope 1 or 2 were detected in 3 patients and agAAB directed against protease-activated receptor (PAR) loop1/2 were seen in 2 patients. AgAAB directed against ETA-receptor loop1 never appeared without agAAB directed against α1-receptor loop1. Immediately after a five day-course of IA agAAB were absent in 81.8 % of the total study group and in 77.8 % of all cases tested positive for agAAB before IA.AgAAB directed against GPCR were identified in TAO patients with a clustering of agAAB directed against α-1-adrenergic receptor loop1 and ETA-receptor loop1. AgAA were eliminated by IA in the majority of cases. We suggest that these agAA play an important role in the pathogenesis of TAO and that their elimination might be responsible for the positive therapeutic effects reported in patients treated with IA.Hintergrund: Histopathologische und serologische Befunde sprechen für eine Immunpathogenese der Thromboangiitis obliterans (TAO, Buerger’sche Erkrankung). Autoantikörper scheinen eine wichtige Rolle im Krankheitsgeschehen zu spielen. Es wurden wiederholt positive therapeutische Effekte durch eine Immunadsorption (IA) gezeigt. Wir analysierten agonistische Autoantikörper (agAAK), die gegen G-Protein gekoppelte Rezeptoren (GPCR) gerichtet sind und analysierten, ob diese durch eine IA effektiv beseitigt werden können. Patienten und Methoden: Zwischen Dezember 2012 und Mai 2014 wurden 11 Patienten mittels IA über 5 konsekutive Tage behandelt. Die agAAK wurden unter Verwendung spezifischer ELISA-Techniken bestimmt. Ergebnisse: AgAAK wurden bei 9 von 11 Patienten (81.8 %) gefunden. Multiple agAAK waren bei 7 Patienten (63.6 %) nachweisbar. Darüber hinaus wurde ein agAAK-Cluster entdeckt, das sich gegen Loop1 des adrenergen α1-Rezeptors und Loop1 des Endothelin A (ETA)-Rezeptors richtet, und sich bei 72.7 % respektive 54.5 % der TAO-Patienten nachweisen ließ. AgAAK gegen Epitop 1 oder 2 des Angiotensin-1-Rezeptors wurden bei 3 Patienten, agAAK gegen Loop1/2 des Proteinase-aktivierten Rezeptor (PAR) wurden bei 2 Patienten nachgewiesen. AgAAK gegen den ETA-Rezeptor traten niemals ohne gleichzeitigen Nachweis von agAAK gegen den α1-adrenergen Rezeptor auf und waren immer gegen Loop1 gerichtet. Unmittelbar nach Beendigung der IA ließen sich bei 81.8 % aller Patienten und bei 77.8 % aller Fälle mit positiven agAAK vor der IA keine agAAK mehr nachgewiesen. Schlussfolgerungen: Wir konnten bei Patienten mit aktiver TAO agAAK gegen GPCR und darüber hinaus ein Antikörper-Cluster nachweisen, das sich bevorzugt gegen Loop1 des α-1-adrenergen Rezeptors und Loop1 des ETA-Rezeptors richtet. Die agAAK wurden mehrheitlich erfolgreich durch die IA eliminiert. Wir sind der Auffassung, dass gegen GPCR-gerichtete agAAK eine wichtige Rolle in der Pathogenese der TAO spielen und ihre Elimination für die publizierten positiven Effekte der IA verantwortlich sein könnten.

The aim of this study was to test the hypothesis that aspirin would reduce the risk for acute coronary syndromes (ACSs) in patients with pneumonia.Pooled data suggest that pneumonia may trigger an ACS as a result of inflammatory reactions and the prothrombotic changes in patients with pneumonia. Hypothetically considering its antiaggregating and anti-inflammatory effects, aspirin might also be beneficial for the primary prevention of ACS in patients with pneumonia.One hundred and eighty-five patients with pneumonia who had more than one risk factor for cardiovascular disease were randomized to an aspirin group (n=91) or a control group (n=94). The patients in the aspirin group received 300 mg of aspirin daily for 1 month. ECGs were recorded on admission and 48 h and 30 days after admission to assess silent ischemia. The level of high-sensitivity cardiac troponin T was measured on admission and 48 h after admission. The primary endpoint was the development of ACS within 1 month. The secondary endpoints included cardiovascular death and death from any cause within 1 month.The χ-test showed that the rates of ACS at 1 month were 1.1% (n=1) in the aspirin group and 10.6% (n=10) in the control group (relative risk, 0.103; 95% confidence interval 0.005-0.746; P=0.015). Aspirin therapy was associated with a 9% absolute reduction in the risk for ACS. There was no significant decrease in the risk of death from any cause (P=0.151), but the aspirin group had a decreased risk of cardiovascular death (risk reduction: 0.04, P=0.044).This randomized open-label study shows that acetyl salicylic acid is beneficial in the reduction of ACS and cardiovascular mortality among patients with pneumonia.

Polymorphisms in DNA repair genes may be associated with differences in the repair efficiency of DNA damage and may influence an individual's risk of atherosclerosis. Genetic research on coronary artery disease (CAD) has traditionally focused on investigation aimed at identifying disease-susceptibility genes. The aim of this study was to investigate the relationship between AP-endonuclease-1 (Asp148Glu), XRCC1 (Arg399Gln), XRCC3 (Thr241Met), XPD (Lys751Gln), XPG (Asp1104His), and hOGG1 (Ser326Cys), gene polymorphisms and the risk of developing CAD in a Turkish population. The study population consisted of 197 patients with acute coronary syndrome (ACS) with chronic CAD and 135 healthy subjects' age and sex matched. Gene polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism method. We demonstrated for the first time, a positive association of XRCC3 and hOGG1 DNA repair gene variants with CAD risk. XRCC3 Thr/Thr genotype and Thr allele frequencies were significantly increased in ACS and chronic CAD patients compared with the control group (p0.05). It was also observed that there is a protective role of XRCC3 Met alleles against both ACS and chronic CAD (p0.05). hOGG1 Cys alleles were found significantly higher in ACS patients than in the control group and carriers of the Cys allele had a 1.7-fold increased risk for ACS. In addition, we confirmed the association of XRCC3 Thr241Met and hOGG1 Ser326Cys gene variants with CAD by haplotype analysis. We found that CAD risk is associated with XRCC3 Thr: hOGG1 Cys haplotype, whereas XRCC3 Met: hOGG1 Ser haplotype was found to be protective against the disease. The preliminary results suggested that XRCC3 and hOGG1 genetic variants may be risk factors by affecting the enzyme's function that may lead to development of CAD.

Angiogenesis and arteriogenesis have a crucial role in the formation of coronary collateral vessels. It has been shown that endocan and vascular cell adhesion molecule-1 (VCAM-1) are potential angiogenetic factors. We investigated the relationship between serum endocan levels and grade of coronary collaterals, and also the correlation of endocan levels with serum VCAM-1 levels. Patients with stable angina and at least one total coronary occlusion at invasive coronary angiography were included in our study. Collateral degree was graded according to Rentrop and Cohen's classification. Patients who had grade 0 or 1 collateral vessels were included in the poorly-developed collateral group, and those with grade 2 or 3 coronary collateral vessels were included in the well-developed collateral group. Serum endocan and VCAM-1 levels were significantly higher in the well-developed collateral group (436.6 ± 213.3 ng/mL vs. 216.1 ± 78.5 ng/mL, p

Background/aims: Endothelial dysfunction is an early and reversible feature in the pathogenesis of atherosclerosis. Coronary flow velocity reserve is a noninvasive test showing endothelial function of epicardial coronary arteries and coronary microcirculatory function. This study was designed to evaluate the carotid intima-media thickness and myocardial microvascular circulation in patients with non-alcoholic fatty liver disease. Materials and Methods: Twenty-four patients with non-alcoholic fatty liver disease and 28 healthy subjects were studied. Ac- cording to the pathology of liver biopsies, patients with non-alcoholic fatty liver disease were divided into non-alcoholic fatty liver and non- alcoholic steatohepatitis groups. Coronary diastolic peak flow velocities were measured at baseline, and then dipyridamole infusion was me- asured by transthoracic Doppler echocardiography. The ratio of hyperemic to baseline diastolic peak velocities was calculated and the inti- ma-media thicknesss of the carotid arteries were measured. Results: Baseline average diastolic peak and diastolic mean flow velocities we- re similar between non-alcoholic fatty liver disease patients and healthy subjects. However, hyperemic average diastolic peak and diastolic mean flow velocities were significantly lower in the patient groups compared to those in the controls (p=0.005 and p=0.002). Coronary flow velocity reserve was 1.65±0.36 and 2.67±0.81 in patients and healthy subjects, respectively (p

Background The use of iodine-based contrast agents entails the risk of contrast induced nephropathy (CIN). Radiocontrast agents elicit the third most common cause of nephropathy among hospitalized patients, accounting for 11-12% of cases. CIN is connected with clinically significant consequences, including increased morbidity, prolonged hospitalization, increased risk of complications, potential need for dialysis, and increased mortality rate. The number of in hospital examinations using iodine-based contrast media has been significantly increasing over the last decade. In order to protect patients from possible complications of such examinations, new biomarkers are needed that are able to predict a risk of contrast-induced nephropathy. Urinary and plasma cyclic guanosine monophosphate (cGMP) concentrations are influenced by renal function. Urinary cGMP is primarily of renal cellular origin. Therefore, we assessed if urinary cGMP concentration may predict major adverse renal events (MARE) after contrast media exposure during coronary angiography. Methods Urine samples were prospectively collected from non-randomized consecutive patients with either diabetes or preexisting impaired kidney function receiving intra-arterial contrast medium (CM) for emergent or elective coronary angiography at the Charite Campus Mitte, University Hospital Berlin. Urinary cGMP concentration in spot urine was analyzed 24 hours after CM exposure. Patients were followed up over 90 days for occurrence of death, initiation of dialysis, doubling of plasma creatinine concentration or MARE. Results In total, 289 consecutive patients were included into the study. Urine cGMP/creatinine ratio 24 hours before CM exposure expressed as mean +/- SD was predictive for the need of dialysis (no dialysis: 89.77 +/- 92.85 mu M/mM, n = 277; need for dialysis: 140.3 +/- 82.90 mu M/mM, n = 12, p = 0.008), death (no death during follow-up: 90.60 +/- 92.50 mu M/mM, n = 280; death during follow-up: 169.88 +/- 81.52 mu M/mM, n = 9; p = 0.002), and the composite endpoint MARE (no MARE: 86.02 +/- 93.17 mu M/mM, n = 271; MARE: 146.64 +/- 74.68 mu M/mM, n = 18, p= 120 mu M/mM before CM exposure is a promising biomarker for the need of dialysis and all-cause mortality 90 days after CM exposure in patients with preexisting renal impairment or diabetes.

Background and purpose: Interferon beta (IFNβ) preparations have some effect on the progressive phase of multiple sclerosis (MS). This limited effect might be partially because of a certain number of IFNβ non-responders. Myxovirus resistance protein A (MxA) – a marker of IFNβ bioactivity – was correlated with the clinical response during an uncontrolled trial, investigating the safety of IFNβ-1b in primary progressive (PPMS) patients. Methods: Twenty PPMS were treated with IFNβ-1b (s.c.) for 1 year. Blood samples were taken before and 1, 2, 3, 6, 9, 12, and 15 months after treatment initiation and MxA protein levels were measured. Patients were clinically evaluated by EDSS and the more sensitive Incapacity Status Scale (ISS) and stratified in a stable and a progressing group. Results: Using ISS criteria, 11 patients remained stable and nine patients progressed during treatment. The mean area under the curve of log MxA levels during treatment were significantly higher in stable than in progressing patients (10.87 vs. 5.99; P = 0.002). Conclusion: A good biological response to IFNβ might be associated with a better clinical effect of this drug and could be helpful in future clinical studies for early identification of treatment responders.