Early changes in pro-inflammatory cytokine levels in neonates with encephalopathy are associated with remote epilepsy.

BackgroundNeonatal seizures are associated with adverse neurologic sequelae including epilepsy in childhood. Here we aim to determine whether levels of cytokines in neonates with brain injury are associated with acute symptomatic seizures or remote epilepsy.MethodsThis is a cohort study of term newborns with encephalopathy at UCSF between 10/1993 and 1/2000 who had dried blood spots. Maternal, perinatal/postnatal, neuroimaging, and epilepsy variables were abstracted by chart review. Logistic regression was used to compare levels of cytokines with acute seizures and the development of epilepsy.ResultsIn a cohort of 26 newborns with neonatal encephalopathy at risk for hypoxic ischemic encephalopathy with blood spots for analysis, diffuse alterations in both pro- and anti-inflammatory cytokine levels were observed between those with (11/28, 39%) and without acute symptomatic seizures. Seventeen of the 26 (63%) patients had >2 years of follow-up and 4/17 (24%) developed epilepsy. Higher levels of pro-inflammatory cytokines IL-6 and TNF-α within the IL-1β pathway were significantly associated with epilepsy.ConclusionsElevations in pro-inflammatory cytokines in the IL-1β pathway were associated with later onset of epilepsy. Larger cohort studies are needed to confirm the predictive value of these circulating biomarkers

Variations, approximation, and low regularity in one dimension

We investigate the properties of minimizers of one-dimensional variational problems when the Lagrangian has no higher smoothness than continuity. An elementary approximation result is proved, but it is shown that this cannot be in general of the form of a standard Lipschitz "variation". Part of this investigation, but of interest in its own right, is an example of a nowhere locally Lipschitz minimizer which serves as a counter-example to any putative Tonelli partial regularity statement. Under these low assumptions we find it nonetheless remains possible to derive necessary conditions for minimizers, in terms of approximate continuity and equality of the one-sided derivatives.Comment: v3, 60 pages. To appear in CoVPDE. Minor cosmetic correction

Early changes in brain structure correlate with language outcomes in children with neonatal encephalopathy.

Global patterns of brain injury correlate with motor, cognitive, and language outcomes in survivors of neonatal encephalopathy (NE). However, it is still unclear whether local changes in brain structure predict specific deficits. We therefore examined whether differences in brain structure at 6 months of age are associated with neurodevelopmental outcomes in this population. We enrolled 32 children with NE, performed structural brain MR imaging at 6 months, and assessed neurodevelopmental outcomes at 30 months. All subjects underwent T1-weighted imaging at 3 T using a 3D IR-SPGR sequence. Images were normalized in intensity and nonlinearly registered to a template constructed specifically for this population, creating a deformation field map. We then used deformation based morphometry (DBM) to correlate variation in the local volume of gray and white matter with composite scores on the Bayley Scales of Infant and Toddler Development (Bayley-III) at 30 months. Our general linear model included gestational age, sex, birth weight, and treatment with hypothermia as covariates. Regional brain volume was significantly associated with language scores, particularly in perisylvian cortical regions including the left supramarginal gyrus, posterior superior and middle temporal gyri, and right insula, as well as inferior frontoparietal subcortical white matter. We did not find significant correlations between regional brain volume and motor or cognitive scale scores. We conclude that, in children with a history of NE, local changes in the volume of perisylvian gray and white matter at 6 months are correlated with language outcome at 30 months. Quantitative measures of brain volume on early MRI may help identify infants at risk for poor language outcomes

Trust/untrust is not the same as true/false. lessons learned and ethical questions on the application of untrustworthiness scales to judge individuals

This special paper reflects on trustworthiness and its implications for scientific medical journals and all the communities they serve: health professionals, policymakers, the public, and a specific discipline, in our case, Physical and Rehabilitation Medicine. We start from a recent episode: a paper claimed the untrustworthiness of two randomised controlled trials (RCTs) published in the European Journal of Physical and Rehabilitation Medicine based on a newly developed trustworthiness scale, used until now only in systematic reviews. This likely represents the first case of applying such a scale focusing on a single leading author. Developing a proper answer to this case led us to present some insights from the perspective of a Journal editor. We discuss the impact of false research results, why trust is needed in science and medicine, the difference between untrust and false results, the problems in judging trustworthiness, the unfortunately weak capacity of the peer review system in preventing these issues, the problems of "post-hoc" judgements and the emerging ethical issues. We conclude with some suggestions for the future based on prevention at the system level

The reliability of gait parameters captured via instrumented walkways: a systematic review and meta-analysis

Introduction: Electronic pressure-sensitive walkways are commonly available solutions to quantitatively assess gait parameters for clinical and research purposes. Many studies have evaluated their measurement properties in different conditions with variable findings. In order to be informed about the current evidence of their reliability for optimal clinical and scientific decision making, this systematic review provided a quantitative synthesis of the test-retest reliability and minimal detectable change of the captured gait parameters across different test conditions (single and cognitive dual-task conditions) and population groups. Evidence acquisition: A literature search was conducted in PubMed, Embase, and Scopus until November 2021 to identify articles that examined the test-retest reliability properties of the gait parameters captured by pressure-sensitive walkways (gait speed, cadence, stride length and time, double support time, base of support) in adult healthy individuals or patients. The methodological quality was rated using the "Consensus-based standards for the selection of health measurement instruments" checklist. Data were meta-analyzed on intraclass correlation coefficient to examine the test-retest relative reliability. Quantitative synthesis was performed for absolute reliability, examined by the weighted average of minimal detectable change values. Evidence synthesis: A total of 44 studies were included in this systematic review. The methodological quality was adequate in half of the included studies. The main finding was that pressure-sensitive walkways are reliable tools for objective assessment of spatial and temporal gait parameters both in singleand cognitive dual-task conditions. Despite few exceptions, the review identified intraclass correlation coefficient higher than 0.75 and minimal detectable change lower than 30%, demonstrating satisfactory relative and absolute reliability in all examined populations (healthy adults, elderly, patients with cognitive impairment, spinocerebellar ataxia type 14, Huntington's disease, multiple sclerosis, Parkinson's disease, rheumatoid arthritis, spinal cord injury, stroke or vestibular dysfunction). Conclusions: Current evidence suggested that, despite different populations and testing protocols used in the included studies, the test-retest reliability of the examined gait parameters was acceptable under single and cognitive dual-task conditions. Further high-quality studies with powered sample sizes are needed to examine the reliability findings of the currently understudied and unexplored pathologies and test conditions

Late complications of robot-assisted radical cystectomy with totally intracorporeal urinary diversion

Introduction and objectives: To evaluate late complications in a large cohort of patients undergoing robot-assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion (ICUD). Materials and methods: We prospectively enrolled patients who underwent RARC and ICUD between August 2012 and June 2019. We excluded patients with Ejection fraction < 36%, retinal vasculopathy, ventriculoperitoneal shunts, and those treated without curative intent. All complications and their onset date have been recorded, defined, and graded according to Clavien classification adapted for radical cystectomy. Results: 210 patients were included, 76% of whom were men, with a mean age of 62 years. Urinary diversions used were Padua Ileal Bladder (PIB) in 80% of cases, and ileal conduit (IC) in 20% of patients (generally older and with more comorbidity). The mean follow-up was 30 ± 22 months. The stenosis rate of uretero-ileal anastomosis was 14%, while a reduction in eGFR (≥ 20%) was observed in about half of the cases. UTIs occurred in 37% of the patients, especially in the first 12 months. Only 2% of patients had bowel occlusion, whereas incisional hernia, lymphocele, and systemic events (metabolic acidosis and major cardiovascular events) occurred respectively in 20%, 10%, and 1% of cases. Conclusions: Our study evaluates first late complications in a cohort of patients who underwent RARC with ICUD. These data are encouraging and in line with findings from a historical series of open radical cystectomy (ORC). This study is a further step in supporting RARC as a safe and effective surgical option for the treatment of muscle-invasive bladder cancer (MIBC) in tertiary referral centers

Accuracy of elastic fusion biopsy in daily practice: results of a multicenter study of 2115 patients

OBJECTIVES: To assess the accuracy of Koelis fusion biopsy for the detection of prostate cancer and clinically significant prostate cancer in the everyday practice. METHODS: We retrospectively enrolled 2115 patients from 15 institutions in four European countries undergoing transrectal Koelis fusion biopsy from 2010 to 2017. A variable number of target (usually 2-4) and random cores (usually 10-14) were carried out, depending on the clinical case and institution habits. The overall and clinically significant prostate cancer detection rates were assessed, evaluating the diagnostic role of additional random biopsies. The cancer detection rate was correlated to multiparametric magnetic resonance imaging features and clinical variables. RESULTS: The mean number of targeted and random cores taken were 3.9 (standard deviation 2.1) and 10.5 (standard deviation 5.0), respectively. The cancer detection rate of Koelis biopsies was 58% for all cancers and 43% for clinically significant prostate cancer. The performance of additional, random cores improved the cancer detection rate of 13% for all cancers (P < 0.001) and 9% for clinically significant prostate cancer (P < 0.001). Prostate cancer was detected in 31%, 66% and 89% of patients with lesions scored as Prostate Imaging Reporting and Data System 3, 4 and 5, respectively. Clinical stage and Prostate Imaging Reporting and Data System score were predictors of prostate cancer detection in multivariate analyses. Prostate-specific antigen was associated with prostate cancer detection only for clinically significant prostate cancer. CONCLUSIONS: Koelis fusion biopsy offers a good cancer detection rate, which is increased in patients with a high Prostate Imaging Reporting and Data System score and clinical stage. The performance of additional, random cores seems unavoidable for correct sampling. In our experience, the Prostate Imaging Reporting and Data System score and clinical stage are predictors of prostate cancer and clinically significant prostate cancer detection; prostate-specific antigen is associated only with clinically significant prostate cancer detection, and a higher number of biopsy cores are not associated with a higher cancer detection rate

Therapeutic Hypothermia for Neonatal Encephalopathy Results in Improved Microstructure and Metabolism in the Deep Gray Nuclei

BACKGROUND AND PURPOSE: Therapeutic hypothermia has reduced morbidity and mortality and is associated with a lower burden of lesions on conventional imaging in NE. However, its effects on brain microstructure and metabolism have not been fully characterized. We hypothesized that therapeutic hypothermia improves measures of brain microstructure and metabolism. MATERIALS AND METHODS: Forty-one neonates with moderate/severe NE (29 treated with hypothermia, 12 nontreated) and 12 healthy neonates underwent MR imaging, DTI, and (1)H-MR spectroscopy. MR imaging scans were scored by the predominant pattern of brain injury: normal, watershed, and BG/thalamus. ADC, FA, Lac:NAA, and NAA:Cho values from bilateral BG and thalamus ROIs were averaged. T test and linear regression analysis were used to determine the association between hypothermia and MR imaging quantitative measures. RESULTS: Conventional MR imaging findings were normal in 41% of treated neonates; all nontreated neonates had brain injury. Values of MR imaging metrics were closer to normal in treated neonates compared with nontreated neonates: ADC was 63% higher in the BG and 116% higher in the thalamus (both P < .05), and Lac:NAA was 76% lower (P = .04) in the BG. Treated neonates with normal MR imaging findings had normal (1)H-MR spectroscopy metabolites, and ADC was higher by 35% in the thalamus (P = .03) compared with healthy neonates. CONCLUSIONS: Therapeutic hypothermia may reduce disturbances of brain metabolism and preserve its microstructure in the setting of NE, possibly by minimizing cytotoxic edema and cell death. Long-term follow-up studies are required to determine whether early post-treatment DTI and (1)H-MR spectroscopy will be useful biomarkers of treatment response