Nickel contamination after minimally-invasive repair of pectus excavatum persists after bar removal

Background Minimally-invasive repair of pectus excavatum (MIRPE) has been shown to be associated with high release of trace metals into patient’s body. The aim of our study was to analyze the kinetics of metal contamination after MIRPE and after bar removal. Methods We prospectively assessed nickel and chromium changes in blood, urine, and local tissue in patients undergoing MIRPE with stainless-steel bar(s). Baseline samples were taken prior to surgery, further samples were taken at six defined time points until 30 months after bar removal. Clinical symptoms were evaluated at the time of every sample collection. Results 28 patients were included (mean age 16.4 years). At four weeks after MIRPE and persisting up to bar removal, we found significantly elevated trace metal levels in blood and urine. Tissue nickel and chromium levels were significantly elevated at the time of bar removal. After bar removal, the concentration of trace metal in urine and the concentration of chromium in plasma decreased gradually. In contrast, nickel levels in blood further increased. Five patients showed irritative symptoms after MIRPE, all symptomatic patients had elevated metal levels. Conclusions Following MIRPE, we found a rapid systemic increase of nickel and chromium. Our data indicate that trace metal release could cause irritative symptoms. The prolonged elevated systemic nickel levels beyond bar removal necessitate further investigations of the long-term side effects of MIRPE

Treatment Strategies and Outcome of the Exstrophy–Epispadias Complex in Germany: Data From the German CURE-Net

Introduction: To evaluate the impact of reconstructive strategies and post-operative management on short- and long-term surgical outcome and complications of classical bladder exstrophy (CBE) patients' comprehensive data of the multicenter German-wide Network for Congenital Uro-Rectal malformations (CURE-Net) were analyzed. Methods: Descriptive analyses were performed between 34 prospectively collected CBE patients born since 2009, median 3 months old [interquartile range (IQR), 2–4 months], and 113 cross-sectional patients, median 12 years old (IQR, 6–21 years). Results: The majority of included individuals were males (67%). Sixty-eight percent of the prospectively observed and 53% of the cross-sectional patients were reconstructed using a staged approach (p = 0.17). Although prospectively observed patients were operated on at a younger age, the post-operative management did not significantly change in the years before and after 2009. Solely, in prospectively observed patients, peridural catheters were used significantly more often (p = 0.017). Blood transfusions were significantly more frequent in males (p = 0.002). Only half of all CBE individuals underwent inguinal hernia repair. Cross-sectional patients after single-stage reconstructions showed more direct post-operative complications such as upper urinary tract dilatations (p = 0.0021) or urinary tract infections (p = 0.023), but not more frequent renal function impairment compared to patients after the staged approach (p = 0.42). Continence outcomes were not significantly different between the concepts (p = 0.51). Self-reported continence data showed that the majority of the included CBE patients was intermittent or continuous incontinent. Furthermore, subsequent consecutive augmentations and catheterizable stomata did not significantly differ between the two operative approaches. Urinary diversions were only reported after the staged concept. Conclusions: In this German multicenter study, a trend toward the staged concept was observed. While single-stage approaches tended to have initially more complications such as renal dilatation or urinary tract infections, additional surgery such as augmentations and stomata appeared to be similar after staged and single-stage reconstructions in the long term

Titanium nitride coating of pectus bar increases metal contamination after minimally-invasive repair of pectus excavatum

Introduction Previous studies demonstrated a release of toxic metals, e.g. nickel and chromium, from stainless steel bars used for minimally invasive repair of pectus excavatum (MIRPE). In the present study, we investigated the impact of titanium nitride coating on the metal release and exposure of MIRPE patients. Material and methods We analyzed the courses of nickel and chromium levels in blood, urine and local tissue in patients undergoing MIRPE with a titanium nitride coated pectus bar between 03/2017 and 10/2018. Sample collection was scheduled prior to MIRPE, at defined postoperative time points and at bar removal. Additionally, we evaluated irritative symptoms. Results were compared to a control group who received uncoated stainless steel bars in a previous time period (03/2015–02/2017). Results 12 patients received coated pectus bars (mean age 15.7 years). The control group included 28 patients. After implantation of a titanium nitride coated bar, significant increase in systemic nickel and chromium levels after one, two and three years was noted. In an interim analysis one year after MIRPE, we observed patients with coated bars to have significantly elevated trace metal values compared to the control group. This elevation persisted throughout the observation period. Tissue metal values were also significantly increased. Irritative symptoms occurred significantly more often in study patients compared to controls (50.0% vs. 14.3%). Conclusions Coating of pectus bars with titanium nitride failed to reduce metal contamination after MIRPE. Instead, it resulted in a significant increase of trace metal levels after MIRPE, compared to patients with stainless steel bars, which may be explained by wear of the coating and inter-component mobilization processes. </jats:sec

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

A century of trends in adult human height

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5-22.7) and 16.5 cm (13.3-19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8-144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries

Trace metal release after minimally-invasive repair of pectus excavatum

Background Several studies have shown a high incidence of metal allergy after minimally-invasive repair of pectus excavatum (MIRPE). We postulated that MIRPE is associated with a significant release of trace metal ions, possibly causing the allergic symptoms. Methods We evaluated the concentration with chromium, cobalt and nickel in blood, urine and tissue in patients prior to MIRPE and in patients who underwent an explantation of the stainless-steel bar(s) after three years. Results Our study group consisted of 20 patients (mean age 19 years) who had bar explantation and our control group included 20 patients (mean age 16 years) prior to MIRPE. At the time of bar removal we detected significantly elevated concentrations of chromium and nickel in the tissue compared to patients prior to the procedure (p<0,001). We also found a significant increase in the levels of chromium in urine and nickel in blood in patients three years post MIRPE (p<0,001). Four patients temporarily developed symptoms of metal allergy, all had elevated metal values in blood and urine at explantation. Conclusions Minimally-invasive repair of pectus excavatum can lead to a significant trace metal exposure

Chromium and nickel concentrations in blood preoperatively and at the time of bar removal.

<p>Bars show mean concentrations of chromium and nickel in blood and error bars show standard error of the mean. The difference between nickel concentrations preoperatively and at the time of bar removal was statistically significant (**p<0.001).</p