Clinical predictors of neurocognitive deficits in children with chronic kidney disease

The purpose of the study was to explore associations between neurocognitive function and chronic kidney disease (CKD)-related clinical characteristics. Twenty-nine children, ages 7 to 19 years, with an estimated creatinine clearance (eCrCl) of 4–89 ml/min per 1.73 m(2) body surface area were enrolled. Intellectual function (IQ), memory, and attention were measured and expressed as age-based standard scores. Clinical data were obtained by physical examination, laboratory testing, parental questionnaires and medical chart review. Pearson correlations and standard Student’s t-tests were used to identify significant (P < 0.05) relationships between targeted clinical variables and neurocognitive scores. Increased CKD severity correlated with lower IQ (P = 0.001) and memory function (P = 0.02). Memory function was lower in children with longer duration of disease (P = 0.03). Similarly, IQ scores were lowest when kidney disease had started at a younger age (P = 0.03) and with a greater percent of life with CKD (P = 0.04). Our findings provide preliminary evidence that increased disease severity, longer duration of disease, and younger age of onset of kidney disease potentially place children with CKD at increased risk of neurocognitive deficits. Additional investigation is required to better quantify these risk factors, particularly regarding how much variability is accounted for by these specific risk factors

Combined Carpal Tunnel Release and Palmar Fasciectomy for Dupuytren’s Contracture Does Not Increase the Risk for Complex Regional Pain Syndrome

Background: Hand surgery dogma suggests that simultaneous surgical treatment of carpal tunnel syndrome (CTS) and Dupuytren’s contracture (DC) results in an increased incidence of Complex Regional Pain Syndrome (CRPS). As a result, many surgeons do not perform surgery for the two conditions concurrently. Our goal was to determine the extent of this association. Methods: We identified all patients undergoing surgical treatment for CTS, DC, or both between April 1982 and March 2017 using the Indiana Network for Patient Care (INPC), a large, multi-institutional, statewide information exchange. Demographics, comorbidities, and 1-year post-operative incidence of CRPS were recorded. Results: A total of 51,739 (95.6%) patients underwent carpal tunnel release (CTR) only, 2,103 (3.9%) underwent palmar fasciectomy (PF) only, and 305 (0.6%) underwent concurrent CTR and PF. There was no difference in the likelihood of developing CRPS (p=0.163) between groups. Independent risk factors for developing CRPS were younger age, anxiety, depression, epilepsy, gout, and history of fracture of the radius, ulna, or the carpus. Conclusions: Concurrent CTR and PF is not associated with an increased risk for developing CRPS. Patient demographics, medical comorbidities, and a history of upper extremity trauma are associated with the development of CRPS after surgery and should be discussed preoperatively as potential risk factors

The nervous system and chronic kidney disease in children

This paper provides a review of the literature on the nervous system involvement incurred by children and adolescents with chronic kidney disease (CKD), with a particular focus on neuropsychological functioning. In addition to an historical overview of earlier literature, published studies from the past 14 years that address both central and peripheral nervous system function in children with CKD are reviewed (1990–2003). These studies span work in neuroimaging, electrophysiology, and neuropsychology. A key focus for this review is on variables that might affect neurodevelopmental status in these children. The paper concludes with suggestions for achieving progress in the understanding of this complication of kidney disease in children

Comparison of Neurologic Trauma and Motorcycle Helmet Use in Drivers vs Passengers

This study compares postcrash prevalences of neurological and head and neck injuries in motorcycle drivers and passengers, stratified by helmet use

Differential Attention Functioning in Pediatric Chronic Kidney Disease

Objective To compare specific attention functions for school-age children with chronic kidney disease (CKD) to those of a typically developing control group. Methods A cross-sectional study examined attention dimensions for children and adolescents with CKD (n = 30) in comparison to a typically developing control group (n = 41). The CKD group consisted of those receiving maintenance dialysis (n = 15) and those with mild/moderate CKD treated conservatively (n = 15). Measures aligning with Mirsky’s conceptual multidimensional model of attention were selected to compare groups across five dimensions of attention: Focus/Execute, Sustain, Stability, Shift, and Encode. Results Significant group differences were revealed, with the CKD group performing worse than controls on the Focus/Execute, Sustain, and Encode dimensions. The CKD group also had a larger proportion of children with scores one standard deviation or more below the mean on the Shift and Encode domains, suggesting an at-risk level of functioning in these dimensions. Secondary analyses showed disease severity to be correlated with worse attention functions for children with CKD. Conclusion Children with CKD may be vulnerable to subtle, specific deficits in numerous attention dimensions relative to their typically developing peers, particularly for those with more severe disease

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Quadruplex DNA: sequence, topology and structure.

G-quadruplexes are higher-order DNA and RNA structures formed from G-rich sequences that are built around tetrads of hydrogen-bonded guanine bases. Potential quadruplex sequences have been identified in G-rich eukaryotic telomeres, and more recently in non-telomeric genomic DNA, e.g. in nuclease-hypersensitive promoter regions. The natural role and biological validation of these structures is starting to be explored, and there is particular interest in them as targets for therapeutic intervention. This survey focuses on the folding and structural features on quadruplexes formed from telomeric and non-telomeric DNA sequences, and examines fundamental aspects of topology and the emerging relationships with sequence. Emphasis is placed on information from the high-resolution methods of X-ray crystallography and NMR, and their scope and current limitations are discussed. Such information, together with biological insights, will be important for the discovery of drugs targeting quadruplexes from particular genes

Assessing Green and Efficient Remediation at Waste Sites

Thousands of contaminated properties and waste sites in the United States cause groundwater pollution. Groundwater remediation systems often rely on electricity generated from non-renewable energy, namely burning fossil fuel. The Massachusetts Department of Environmental Protection (MassDEP) has been promoting energy efficiency and renewable energy sources to reduce greenhouse gas emissions associated with groundwater remediation. Our team utilized MA waste site data, MassDEP databases and remedial monitoring reports, a site visit, and interviews to determine if green and efficient energy applications are viable in the remediation process. Gains in energy efficiency from system component modifications and use of solar power can effectively reduce greenhouse gas emissions

Combined Carpal Tunnel Release and Palmar Fasciectomy for Dupuytren’s Contracture Does Not Increase the Risk for Complex Regional Pain Syndrome

Background: Hand surgery dogma suggests that simultaneous surgical treatment of carpal tunnel syndrome (CTS) and Dupuytren’s contracture (DC) results in an increased incidence of Complex Regional Pain Syndrome (CRPS). As a result, many surgeons do not perform surgery for the two conditions concurrently. Our goal was to determine the extent of this association. Methods: We identified all patients undergoing surgical treatment for CTS, DC, or both between April 1982 and March 2017 using the Indiana Network for Patient Care (INPC), a large, multi-institutional, statewide information exchange. Demographics, comorbidities, and 1-year post-operative incidence of CRPS were recorded. Results: A total of 51,739 (95.6%) patients underwent carpal tunnel release (CTR) only, 2,103 (3.9%) underwent palmar fasciectomy (PF) only, and 305 (0.6%) underwent concurrent CTR and PF. There was no difference in the likelihood of developing CRPS (p=0.163) between groups. Independent risk factors for developing CRPS were younger age, anxiety, depression, epilepsy, gout, and history of fracture of the radius, ulna, or the carpus. Conclusions: Concurrent CTR and PF is not associated with an increased risk for developing CRPS. Patient demographics, medical comorbidities, and a history of upper extremity trauma are associated with the development of CRPS after surgery and should be discussed preoperatively as potential risk factors