Severe neurological outcomes after very early bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD)

To test the association between bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD) and long-term clinical outcome and to identify risk factors for severe outcomes, a dataset comprising 504 patients from the international registry study ARegPKD was analyzed for characteristics and complications of patients with very early (� 3 months; VEBNE) and early (4�15 months; EBNE) bilateral nephrectomies. Patients with very early dialysis (VED, onset � 3 months) without bilateral nephrectomies and patients with total kidney volumes (TKV) comparable to VEBNE infants served as additional control groups. We identified 19 children with VEBNE, 9 with EBNE, 12 with VED and 11 in the TKV control group. VEBNE patients suffered more frequently from severe neurological complications in comparison to all control patients. Very early bilateral nephrectomies and documentation of severe hypotensive episodes were independent risk factors for severe neurological complications. Bilateral nephrectomies within the first 3 months of life are associated with a risk of severe neurological complications later in life. Our data support a very cautious indication of very early bilateral nephrectomies in ARPKD, especially in patients with residual kidney function, and emphasize the importance of avoiding severe hypotensive episodes in this at-risk cohort. © 2020, The Author(s)

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol�which is a marker of cardiovascular risk�changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95 credible interval 3.7 million�4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world. © 2020, The Author(s), under exclusive licence to Springer Nature Limited

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)

In Vivo Multiphoton Microscopy of Basal Cell Carcinoma

IMPORTANCE: Basal cell carcinomas (BCCs) are diagnosed by clinical evaluation, which can include dermoscopic evaluation, biopsy, and histopathologic examination. Recent translation of multiphoton microscopy (MPM) to clinical practice raises the possibility of noninvasive, label-free in vivo imaging of BCCs that could reduce the time from consultation to treatment. OBJECTIVES: To demonstrate the capability of MPM to image in vivo BCC lesions in human skin, and to evaluate if histopathologic criteria can be identified in MPM images. DESIGN, SETTING, AND PARTICIPANTS: Imaging in patients with BCC was performed at the University of California–Irvine Health Beckman Laser Institute & Medical Clinic, Irvine, between September 2012 and April 2014, with a clinical MPM-based tomograph. Ten BCC lesions were imaged in vivo in 9 patients prior to biopsy. The MPM images were compared with histopathologic findings. MAIN OUTCOMES AND MEASURES: MPM imaging identified in vivo and noninvasively the main histopathologic feature of BCC lesions: nests of basaloid cells showing palisading in the peripheral cell layer at the dermoepidermal junction and/or in the dermis. RESULTS: The main MPM feature associated with the BCC lesions involved nests of basaloid cells present in the papillary and reticular dermis. This feature correlated well with histopathologic examination. Other MPM features included elongated tumor cells in the epidermis aligned in 1 direction and parallel collagen and elastin bundles surrounding the tumors. CONCLUSIONS AND RELEVANCE: This study demonstrates, in a limited patient population, that noninvasive in vivo MPM imaging can provide label-free contrast that reveals several characteristic features of BCC lesions. Future studies are needed to validate the technique and correlate MPM performance with histopathologic examination

Measurement of the differential inclusive B+ hadron cross sections in pp collisions at s=13 TeV

The differential cross sections for inclusive production of B+ hadrons are measured as a function of the B+ transverse momentum pT B and rapidity yB in pp collisions at a centre-of-mass energy of 13 TeV, using data collected by the CMS experiment that correspond to an integrated luminosity of 48.1 pb−1. The measurement uses the exclusive decay channel B+→J/ψK+, with J/ψ mesons that decay to a pair of muons. The results show a reasonable agreement with theoretical calculations within the uncertainties. © 2017 The Author(s

Treatment and long-term outcome in primary distal renal tubular acidosis

BACKGROUND: Primary distal renal tubular acidosis (dRTA) is a rare disorder, and we aimed to gather data on treatment and long-term outcome. METHODS: We contacted paediatric and adult nephrologists through European professional organizations. Responding clinicians entered demographic, biochemical, genetic and clinical data in an online form. RESULTS: Adequate data were collected on 340 patients (29 countries, female 52). Mutation testing had been performed on 206 patients (61); pathogenic mutations were identified in 170 patients (83). The median (range) presentation age was 0.5 (0-54) years and age at last follow-up was 11.0 (0-70.0) years. Adult height was slightly below average with a mean (SD score) of -0.57 (±1.16). There was an increased prevalence of chronic kidney disease (CKD) Stage �2 in children (35) and adults (82). Nephrocalcinosis was reported in 88. Nephrolithiasis was more common with SLC4A1 mutations (42 versus 21). Thirty-six percent had hearing loss, particularly in ATP6V1B1 (88). The median (interquartile range) prescribed dose of alkali (mEq/kg/day) was 1.9 (1.2-3.3). Adequate metabolic control (normal plasma bicarbonate and normocalciuria) was achieved in 158 patients (51), more commonly in countries with higher gross domestic product (67 versus 23), and was associated with higher height and estimated glomerular filtration rate. CONCLUSION: Long-term follow-up from this large dRTA cohort shows an overall favourable outcome with normal adult height for most and no patient with CKD Stage 5. However, 82 of adult patients have CKD Stages 2-4. Importance of adequate metabolic control was highlighted by better growth and renal function but was achieved in only half of patients. © The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved

Major results from the first plasma campaign of the Wendelstein 7-X stellarator

After completing the main construction phase of Wendelstein 7-X (W7-X) and successfully commissioning the device, first plasma operation started at the end of 2015. Integral commissioning of plasma start-up and operation using electron cyclotron resonance heating (ECRH) and an extensive set of plasma diagnostics have been completed, allowing initial physics studies during the first operational campaign. Both in helium and hydrogen, plasma breakdown was easily achieved. Gaining experience with plasma vessel conditioning, discharge lengths could be extended gradually. Eventually, discharges lasted up to 6 s, reaching an injected energy of 4 MJ, which is twice the limit originally agreed for the limiter configuration employed during the first operational campaign. At power levels of 4 MW central electron densities reached 3  ×  1019 m−3, central electron temperatures reached values of 7 keV and ion temperatures reached just above 2 keV. Important physics studies during this first operational phase include a first assessment of power balance and energy confinement, ECRH power deposition experiments, 2nd harmonic O-mode ECRH using multi-pass absorption, and current drive experiments using electron cyclotron current drive. As in many plasma discharges the electron temperature exceeds the ion temperature significantly, these plasmas are governed by core electron root confinement showing a strong positive electric field in the plasma centre