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OBJECTIVE Epidural hematoma (EDH) has rarely been studied specifically in infants. The objective of this study was to investigate the outcomes of patients aged < 18 months (infants) with EDH. METHODS The authors conducted a single-center retrospective study of 48 infants aged less than 18 months who underwent an operation for a supratentorial EDH in the last decade. Clinical, radiological, and biological variables were used in a statistical analysis to identify factors predictive of radiological and clinical outcome. RESULTS Forty-seven patients were included in the final analysis. Seventeen children (36%) had cerebral ischemia on postoperative imaging, either due to stroke (cerebral herniation) or by local compression. Factors associated with ischemia after multivariate logistic regression were the presence of an initial neurological deficit (76% vs 27%, p = 0.03), low platelet count (mean 192 vs 267 per mm3, p = 0.01), low fibrinogen level (mean 1.4 vs 2.2 g/L, p = 0.04) and long intubation time (mean 65.7 vs 10.1 hours, p = 0.03). Cerebral ischemia on MRI was predictive of a poor clinical outcome. CONCLUSIONS Infants with EDH have a low mortality rate but a high risk of cerebral ischemia, along with long-term neurological sequelae.

Background Focal cortical dysplasias (FCD) are a frequent cause of drug-resistant epilepsy in children but are often undetected on structural magnetic resonance imaging (MRI). We aimed to measure and validate the variation of resting state functional MRI (rs-fMRI) blood oxygenation level dependent (BOLD) metrics in surgically proven FCDs in children, to assess the potential yield for detecting and understanding these lesions. Methods We prospectively included pediatric patients with surgically proven FCD with inconclusive structural MRI and healthy controls, who underwent a ten-minute rs-fMRI acquired at 3T. Rs-fMRI data was pre-processed and maps of values of regional homogeneity (ReHo), degree centrality (DC), amplitude of low frequency fluctuations (ALFF) and fractional ALFF (fALFF) were calculated. The variations of BOLD metrics within the to-be-resected areas were analyzed visually, and quantitatively using lateralization indices. BOLD metrics variations were also analyzed in fluorodeoxyglucose-positron emission tomography (FDG-PET) hypometabolic areas. Results We included 7 patients (range: 3–15 years) and 6 aged-matched controls (range: 6–17 years). ReHo lateralization indices were positive in the to-be-resected areas in 4/7 patients, and in 6/7 patients in the additional PET hypometabolic areas. These indices were significantly higher compared to controls in 3/7 and 4/7 patients, respectively. Visual analysis revealed a good spatial correlation between high ReHo areas and MRI structural abnormalities (when present) or PET hypometabolic areas. No consistent variation was seen using DC, ALFF, or fALFF. Conclusion Resting-state fMRI metrics, noticeably increase in ReHo, may have potential to help detect MRI-negative FCDs in combination with other morphological and functional techniques, used in clinical practice and epilepsy-surgery screening.

ContextEndocrine complications are common in pediatric brain tumor patients.ObjectiveTo describe hypothalamic–pituitary–gonadal axis (HPGA) function in patients treated in childhood for a primary brain tumor more than 5 years earlier, in order to identify risk factors for HPGA impairment.MethodsWe retrospectively included 204 patients diagnosed with a primary brain tumor before 18 years of age and monitored at the pediatric endocrinology unit of the Necker Enfants-Malades University Hospital (Paris, France) between January 2010 and December 2015. Patients with pituitary adenoma or untreated glioma were excluded.ResultsAmong patients with suprasellar glioma not treated by radiotherapy, the prevalence of advanced puberty was 65% overall and 70% when the diagnosis occurred before 5 years of age. Medulloblastoma chemotherapy caused gonadal toxicity in 70% of all patients and in 87.5% of those younger than 5 years at diagnosis. In the group with craniopharyngioma, 70% of patients had hypogonadotropic hypogonadism, which was consistently accompanied by growth hormone deficiency.ConclusionTumor type, location, and treatment were the risk main factors for HPGA impairment. Awareness that onset can be delayed is essential to guide information of parents and patients, patient monitoring, and timely hormone replacement therapy.

Context Endocrine complications are common in pediatric brain tumor patients. Objective We aimed to describe the endocrine follow-up of patients with primary brain tumors. Methods This is a noninterventional observational study based on data collection from medical records of 221 patients followed at a Pediatric Endocrinology Department. Results Median age at diagnosis was 6.7 years (range, 0-15.9), median follow-up 6.7 years (0.3-26.6), 48.9% female. Main tumor types were medulloblastoma (37.6%), craniopharyngioma (29.0%), and glioma (20.4%). By anatomic location, 48% were suprasellar (SS) and 52% non-suprasellar (NSS). Growth hormone deficiency (GHD) prevalence was similar in both groups (SS: 83.0%, NSS: 76.5%; P = 0.338), appearing at median 1.8 years (−0.8 to 12.4) after diagnosis; postradiotherapy GHD appeared median 1.6 years after radiotherapy (0.2-10.7). Hypothyroidism was more prevalent in SS (76.4%), than NSS (33.9%) (P < 0.001), as well as ACTH deficiency (SS: 69.8%, NSS: 6.1%; P < 0.001). Early puberty was similar in SS (16%) and NSS (12.2%). Hypogonadotropic hypogonadism was predominant in SS (63.1%) vs NSS (1.3%), P < 0.001, and postchemotherapy gonadal toxicity in NSS (29.6%) vs SS (2.8%), P < 0.001. Adult height was lower for NSS compared to target height (−1.0 SD, P < 0.0001) and to SS patients (P < 0.0001). Thyroid nodules were found in 13/45 patients (28.8%), including 4 cancers (4.8-11.5 years after radiotherapy). Last follow-up visit BMI was higher in both groups (P = 0.0001), and obesity incidence was higher for SS (46.2%) than NSS (17.4%). Conclusion We found a high incidence of early-onset endocrine disorders. An endocrine consultation and nutritional evaluation should be mandatory for all patients with a brain tumor, especially when the tumor is suprasellar or after hypothalamus/pituitary irradiation.

The COVID-19 pandemic and the containment and mitigation measures taken were feared to be associated with increased child abuse.To investigate the trend of abusive head trauma (AHT) incidence and severity in infants during the COVID-19 pandemic.In a time-series analysis of a longitudinal, population-based, cohort study, all consecutive cases of AHT in infants younger than 12 months old referred between January 2017 and December 2021 to Necker Hospital for Sick Children, the single regional pediatric neurosurgery center for the Paris metropolitan area, were included. AHT was defined as 1 or more subdural hemorrhage and a positive multidisciplinary evaluation after a social, clinical, biological, and radiological workup. Data were analyzed from January to March 2022.The primary outcome was the monthly incidence of AHT, which was analyzed using Poisson regression modeling. Secondary outcomes included mortality and severe morbidity and were studied with logistic and linear regressions. The monthly incidence of neurosurgical interventions for hydrocephalus was used as a control series.Among the 99 included infants with AHT (median [IQR] age, 4 [3-6] months; 64 boys [65%]), 86 of 99 (87%) had bridging vein thrombosis, 74 of 99 (75%) had retinal hemorrhages, 23 of 72 (32%) had fractures, 26 of 99 (26%) had status epilepticus, 20 of 99 (20%) had skin injuries, 53 of 99 (54%) underwent neurosurgical interventions, and 13 of 99 (13%) died. Compared with the prepandemic period (2017-2019), AHT incidence was stable in 2020 (adjusted incidence rate ratio, 1.02; 95% CI, 0.59-1.77) and then significantly increased in 2021 (adjusted incidence rate ratio, 1.92; 95% CI, 1.23-2.99). The severity of AHT worsened in 2021 in terms of mortality (odds ratio 9.39; 95% CI, 1.88-47.00). Other secondary outcomes and the control series were not significantly modified.In this cohort study, a marked increase in AHT incidence and severity occurred during the COVID-19 pandemic in the Paris metropolitan area. These results suggest the need for clinical awareness and preventive actions.

BackgroundCandida auris is a worldwide emerging pathogen known for causing infections and outbreaks in health care settings. In Orange County, CA, C. auris has been circulating and causing outbreaks in long term care facilities since 2019, with a total of 1,017 cases detected from February 2019 to December 2021.ObjectiveTo evaluate an rt-PCR assay for rapid identification and assessment of colonization of C. auris from patient surveillance samples at the OC Public Health Laboratory.MethodAn extraction protocol using the MasterPure kit and automated EZ1 Advanced XL followed by rt-PCR using PerfeCTa Multiplex qPCR TaqMan, and the 7500 Fast Dx was conducted. The assay was evaluated using 131 previously confirmed patient samples and 123 prospective fresh samples from different body sites.ResultsThe assay was highly reproducible at an LOD of 230 CFU/ml. The sensitivity and specificity of the 131 samples was 90 % and 86 % respectively and for the 123 samples it was 93% and 90% respectively. ROC analysis was calculated using all samples (n = 254) to determine the most ideal diagnostic value. The AUC was 0.922 and optimal cutoff was a cycle threshold 36.78. A CT ≤37.00 is the ideal diagnostic value for patient surveillance samples.ConclusionThe successful implementation of the rt-PCR assay for C. auris in a local public health laboratory allows for accurate and rapid screening and identification of C. auris which can contribute to enhanced surveillance and control of C. auris spread in local health care facilities.

Background and Purpose: Significant hemorrhage expansion (sHE) is a known predictor of poor outcome after an intracerebral hemorrhage (ICH) in adults but remains poorly reported in children. In a large inception cohort, we aimed to explore the prevalence of sHE, its associations with clinical outcomes, and its clinical-imaging predictors in children. Methods: Children admitted between January 2000 and March 2020 at a quaternary care pediatric hospital were screened for inclusion. Sample was restricted to children with 2 computed tomography scans within 72 hours of ICH onset, and a minimal clinical follow-up of months. sHE was defined as an increase from baseline ICH volume by 6 cc or 33% on follow-up computed tomography. Clinical outcome was assessed at 12 months with the King’s Outcome Scale for Childhood Head Injury score and defined as favorable for scores ≥5. Results: Fifty-two children met inclusion criteria, among which 8 (15%) demonstrated sHE, and 18 (34.6%) any degree of expansion. Children with sHE had more frequent coagulation disorders (25.0% versus 2.3%; P =0.022). After multivariable adjustment, only the presence of coagulation disorders at baseline remained independently associated with sHE (adjusted odds ratio, 14.4 [95% CI, 1.04–217]; P =0.048). sHE was independently associated with poor outcome (King’s Outcome Scale for Childhood Head Injury P =0.043). Conclusions: sHE is a frequent phenomenon after admission for a pediatric ICH and more so in children with coagulation defects. As sHE was strongly associated with poorer clinical outcomes, these data mandate a baseline coagulation work up and questions the need for protocolized repeat head computed tomography in children admitted for pediatric ICH.

A coronavirus (SARS-CoV-2) has caused a global pandemic and associated morbidity and mortality resultant from COVID-19. As a result of efforts to control direct (person to person) and indirect (contaminated objects, surfaces, indoor air) transmission of the virus, various interventions have been evaluated. Studies were conducted to evaluate the efficacy of commercially available chlorine dioxide (CD) products to reduce viral loads on PPE (face masks) and surfaces using a novel dry gas release intervention. The efficacy of CD slow release 30-day sachets was tested on N95 face masks inoculated with human coronavirus OC43 in suspension. One sachet was placed with an inoculated mask in plastic resealable bags. Three trials were completed using the original sachet where a mask and sachet were placed into a plastic bag for 13 hours per sachet age of 1 day, 14 days, and 30 days. The amount of CD generated during a 13-hour treatment period was 0.30 mg. The nominal concentration of CD was estimated to be 317 mg/m3. All three tests demonstrated at least a 99.91% reduction of viral loading in the mask versus a non-treated control. Efficacy of CD dry gas fast releasing pods (Ultrashok) for fumigation was also tested in a 1344 ft3 closed room. Two pods were placed in the space and CD surface virucidal efficacy was tested in three locations of the room after 1 hour and 2 hours of dwell time. The estimated nominal peak concentration was 15 ppmv in the room. The one-hour exposure saw a >99.91% OC43 reduction on surfaces and the two-hour exposure resulted in a >99.997% OC43 reduction on surfaces versus a non-treated control. These results indicate dry CD is highly effective against human coronavirus. CD was 99.91% effective for eliminating human coronavirus OC43 in both sachet and capsule fumigant form using both fast and slow release mechanisms. Rapid fumigant application is suitable for contaminated rooms, ambulances, emergency vehicles, and many types of PPE, most particularly porous PPE materials. The gaseous state of CD allows for rapid diffusion and transfer of the virucidal stable free radical to all surfaces of PPE and indoor areas that would favor virus survival. Additionally, this work suggests CD can be effective at levels with significant margins of safety (little to no exposure and rapid degradation of residuals) providing minimal public health risks associated with the use of CD.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are found in some consumer products due to their heat resistance and durability. However, there is potential for these substances to bioaccumulate in humans. It is relevant to investigate biological effects of these chemicals, as studies have suggested early life exposure may impact human developmental outcomes such as infant birth weight and youth adiposity. The objective of the current study was to determine if a relationship exists between increasing levels of certain PFAS and anthropometrics in adolescents ages 12 - 18. The three PFAS examined were: perfluorodecanoic acid (PFDeA), 2-(N-methyl-perfluoroctane sulfonamido) acetic acid (Me-PFOSA-AcOH), and perfluoroundecanoic acid (PFUA). The data was obtained from the National Health and Nutrition Examination Survey (NHANES) from the years 2011-2012 (N = 287) and 2013-2014 (N = 344). An additional analysis combined data from 3 NHANES survey cycles using sampling weights for the years 2011-2016 (N = 875) to generate a larger sample size of detectable PFAS. PFAS concentrations were classified as above or below the lower limit of detection (LLOD) to evaluate differences in weight, waist circumference, BMI (body mass index), and height using Student’s t-tests. These same anthropometric outcomes were examined as continuous variables in linear regression models and were stratified by sex. In the 2013-2014 dataset, there were significant inverse associations between female concentrations of PFUA and PFDeA with waist circumference (PFUA β = −0.056; 95% CI, −0.106, −0.005; PFDeA β = −0.06; 95% CI, −0.10, −0.02), weight-for-age z-score (PFUA β = −0.40; 95% CI, −0.74, −0.05; PFDeA β = −0.38; 95% CI, −0.64, −0.12), and BMI-for-age z-score (PFUA β = −0.48; 95% CI, −0.86, −0.10; PFDeA β = −0.45; 95% CI, −0.73, −0.16). In the 2011-2012 dataset, males displayed a significant inverse relationship between PFDeA and waist circumference (β = −0.08; 95% CI, −0.14, −0.02), weight-for-age z-score (β = −0.49; 95% CI, −0.88, −0.11), and BMI-for-age z-score (β = −0.44; 95% CI, −0.84, −0.05). In the combined analysis of NHANES years 2011-2016, there were significant inverse associations with PFUA and PFDeA and weight-for-age z-score, waist circumference, and BMI-for-age z-score. In the given sample years, there was no compelling evidence for a relationship between any of the perfluoroalkyl chemicals and height, nor between Me-PFOSA-AcOH and any of the body measures after adjusting for age, sex, and race/ethnicity. This suggests that PFUA and PFDeA exposure in adolescents may be related to smaller waist circumference, weight, and BMI, but longitudinal studies are recommended to confirm these findings.

BackgroundMeningioangiomatosis is a poorly studied, rare, benign, and epileptogenic brain lesion.ObjectiveTo demonstrate that surgical resection and a short-time interval to surgery improves epileptic seizure control, we performed a systematic review and meta-analysis of meningioangiomatosis cases.MethodsUsing PRISMA-IPD guidelines, the authors performed a systematic review and meta-analysis of histopathologically-proven meningioangiomatosis cases. Literature search in French and English languages (PubMed, Embase, the Cochrane Library, and the Science Citation Index) including all studies (January 1981 to June 2020) dealing with histopathologically-proven meningioangiomatosis, without age restriction. We assessed clinical, imaging, histomolecular, management, and outcome findings of patients with meningioangiomatosis.ResultsTwo-hundred and seven cases of meningioangiomatosis from 78 studies were included. Most meningioangiomatosis was sporadic, preferentially concerned male patients, younger than 20 years old, and allowed a functionally independent status. Epileptic seizure was the main symptom, with 81.4% of patients having uncontrolled seizures at the time of surgery. Meningioangiomatosis mainly had frontal (32.3%) or temporal (30.7%) locations. Imaging presentation was heterogeneous, and the diagnosis was often missed preoperatively. The histopathologic pattern was similar whatever the clinical presentation, and immunohistochemistry had limited diagnostic value. On molecular analysis, allelic loss at 22q12 was more frequent in samples of meningioangiomatosis-associated meningioma (37.5%) than in isolated meningioangiomatosis (23.1%). Time interval from diagnosis to surgery (p = 0.011) and lack of surgical resection of the meningioangiomatosis (p = 0.009) were independent predictors of postoperative seizure control.ConclusionsOwing to low scientific evidence, a multicentric prospective study should help refining the management of meningioangiomatosis.

The spatial distribution of individuals within populations can result in fine-scale density dependence and affect the social environment that is encountered. As such, it is important to quantify within-population spatial structuring and understand the factors that shape it. In this study, we make use of point process statistics to test whether colony size affects the statistical type of spatial nest distribution produced by common terns (Sterna hirundo) breeding at identical manmade rectangular and homogeneous islands of fixed physical size. Comparing subcolonies of variable density both within and across years, we find that inter-nest distances are smaller at higher local and overall breeding density, but that the spatial distribution type does not vary across the observed densities. This suggests that the birds’ main settlement rules do not depend on density. In our case, analyses of fine-scale density dependence or potential social effects therefore do not need to account for between-individual heterogeneity in settlement decision rules or acceptance of these rules. We urge, however, other studies to similarly test for density dependence of the spatial distribution of individuals before undertaking such “downstream” analyses.

Although considerable research has been conducted regarding airborne lead exposures during lead paint removal, little data has been collected measuring the lead concentration on workers’ hands in the construction industry. As a result, there are gaps in our understanding of the effectiveness of a standard work practice control (handwashing) in the prevention and control of elevated blood lead levels (BLLs) in the workplace. The primary objective of this study was to assess if a National Institute for Occupational Safety and Health (NIOSH) formulation intended to remove lead from skin (Hygenall© LeadoffTM Foaming Soap) is more effective than a commonly used soap in the industrial painting industry (Zep Cherry Bomb Soap) in reducing the concentration of lead on workers’ hands after exposure. A secondary aim was to assess if using LeadoffTM Foaming Soap during handwashing reduces worker uptake of lead on bridge painting projects. We evaluated hand wipe, air sample and blood lead level data collected by two industrial bridge painting contractors. Airborne exposures ranged from 350 μg/m3 to 19,700 μg/m3. The geometric mean lead concentration remaining on workers’ hands after using Zep Cherry Bomb Soap was 77 μg per hand wipe compared with 61 μg per hand wipe after use of LeadoffTM Foaming Soap for all work classifications. The geometric lead concentration on workers’ hands decreased by 16 μg/hand wipe for all work classifications combined after using LeadoffTM Foaming Soap—a decrease of 21%. The use of Hygenall LeadoffTM Foaming Soap reduced the maximum lead concentration on workers’ hands by 85%. The geometric mean BLL for all work classifications was 12.1 μg/dl before the use of LeadoffTM. After two months of airborne exposure and use of LeadoffTM Foaming Soap at breaks and at the end of the workday, the geometric mean BLL for all work classifications increased to 18.1 μg/dl. Worker BLLs increased despite the reduction in the concentration of lead measured on workers’ hands—most likely a result of ineffective inhalation exposure controls. We found that the LeadoffTM Foaming Soap was more effective in removing lead from workers’ hands than Zep Cherry Bomb.

Objective: The purpose of the investigation is to determine if a relationship exists between heart rate and urinary biomarkers of chronic, subacute chlorpyrifos pesticide exposure in youth. Methods: Using 2001-2002 NHANES data, a sample of 1233 children ages 6 - 18 was grouped based on detection status of 3,5,6-trichloropyridinol (TCPy) in urine. Radial pulse and brachial pulse were recorded as measures of heart rate by physicians. T-tests and linear regression analyses were performed to test for associations between TCPy concentrations and heart rate. Results: None of the associations between TCPy levels and heart rate outcomes were found to be significant. Nonsignificant effects in the TCPy-detected groups included a slightly reduced heart rate in girls, as well as a slightly elevated heart rate in boys when compared to the undetected controls. Neither was there any significant observable difference in heart rate due to detection status in the sample overall. Conclusions: At this time, an effect on heart rate attributable to chronic, low-level chlorpyrifos exposure in youth cannot be determined. Children and adolescents detected did not demonstrate a substantial change in pulse measures when compared to controls. It is recommended that subsequent studies examine chlorpyrifos biomarkers as they may relate to other indicators of cardiovascular health.

Chemistry educators have a responsibility to teach students about the essential role the field of chemistry has in a sustainable future for the planet. Chemical products, such as pharmaceuticals, p...

ObjectiveThe aim of this study was to better characterise clinical presentation, management and outcome in infants and children with brain abscess.MethodsThe authors conducted a retrospective, multicentre study in two national reference centres over a 25-year period (1992–2017). During this period, 116 children and 28 infants (age ResultsThe median age at diagnosis was 101.5 (range: 13–213) months in children and 1 (0–11) month in infants. Significant differences were observed between children and infants. The most common predisposing factor was meningitis in infants (64% of cases vs 3% in children), while it was otolaryngology-related infection in children (31% of cases vs 3.6% in infants). Infants presented more frequently with fever and meningism compared with children. 115 patients were treated with aspiration and 11 with excision. Reoperation was required in 29 children vs 1 infant. The overall mortality rate was 4% (3.4% for children, 7.1% for infants). At 3-month follow-up, the outcome was favourable in 86% of children vs in 68% of infants.ConclusionThere is a clear difference between children and infants with brain abscess in terms of predisposing factors, causative organisms and outcome. Despite surgical drainage and directed antibiotic therapy, 25% of patients with brain abscess require reoperation. Mortality is improved compared with historical series; however, long-term morbidity is significant particularly in the infant population.

To evaluate the effectiveness of personal hygiene (handwashing) amongst workers at industrial sites to remove lead from their hands, a retrospective analysis of hand wipe samples was conducted using data collected by two contractors from two bridge painting projects for total lead using method ASTM E-1979-17/EPA SW846 7000B. Exposures resulted from the removal of lead-based paint from the structure and trace elements of lead found in the abrasive blast media. In total, six work tasks were evaluated and sixty unique hand wipe samples were evaluated. Thirty samples were collected during the worker’s lunch break, after they had reportedly washed their hands with a further 30 collected at the end of the workday following the same protocol. To be included in this evaluation, the contractors were required to follow NIOSH Method 9105 (Lead in Dust Wipes-Dermal Surfaces) with subsequent analysis of samples for total lead by an American Industrial Hygiene Association (AIHA) accredited laboratory. All 60 samples contained detectable lead. The lead exposures ranged from 19.5 μg to 3420 μg. The geometric mean for the samples collected was 337 μg. These results indicate that current personal hygiene practices at the evaluated sites are not effective at removing lead from worker’s hands during and after the workday. They also suggest that the residual lead measured on the workers’ hands, at the end of the shift, is likely contributing to the elevated blood lead levels in this population.

Protein kinase C-iota (PKC-ι) is an oncogene overexpressed in many cancer cells including prostate, breast, ovarian, melanoma, and glioma. Previous in-vitro studies have shown that 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide (ICA-1s), a PKC-ι specific inhibitor, is effective against some cancer cell lines by decreasing cell growth and inducing apoptosis. To assess ICA-1s as a possible therapeutic, in-vivo studies using a murine model were performed. ICA-1s was tested for stability in blood serum and results demonstrated that ICA-1s was stable in human plasma at 25 and 37°C over a course of 2 h. Toxicity of ICA-1s was tested for both acute and subacute exposure. The acute exposure showed patient surviving after 48 h of doses ranging from 5 to 5000 mg/kg. Subacute tests exposed the patients to 14 days of treatment and were followed by serum and tissue collection. Aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, troponin, and C-reactive protein serum levels were measured to assess organ function. ICA-1s in plasma serum was measured over the course of 24 h for both oral and intravenous treatments. Heart, liver, kidney, and brain tissues were analyzed for accumulation of ICA-1s. Finally, athymic nude mice were xenografted with DU-145 prostate cancer cells. After tumors reached ~0.2 cm2, they were either treated with ICA-1s or left as control and measured for 30 days or until the tumor reached 2 cm2. Results showed tumors in treated mice grew at almost half the rate as untreated tumors, showing a significant reduction in growth. In conclusion, ICA-1s is stable, shows low toxicity, and is a potential therapeutic for prostate carcinoma tumors.

OBJECTIVE The authors’ objective was to study clinical, imaging, and neuropsychological changes in children who underwent surgery for a temporal arachnoid cyst (TAC). METHODS Thirty-four children were prospectively assessed similarly at diagnosis and postoperatively (mean 14 months) with clinic visits, images, cognitive tests, and parental questionnaires on mood/behavior and executive functions. The scores were compared pre- and postoperatively for the entire cohort and individually. The scores of 25 children were also compared with a control group of 23 healthy age-matched children. Parents were administered an outcome questionnaire on average 4 years postoperatively. RESULTS The 34 children selected for surgery had signs of raised intracranial pressure (74%) and/or selective neuropsychological disorders presumably linked to cyst location (learning difficulties in 65%, cognitive difficulties in 56%, and mood/behavior difficulties in 47%). The majority of patients had a convex cyst (85%) and underwent microsurgical fenestration (85%). The TAC volume decreased ≥ 50% for 59% of children. On the Wechsler Intelligence Scale, the entire cohort significantly improved on Full Scale IQ and verbal and perceptual nonverbal indexes. Individually, nearly half of the children (47%) highly increased their scores (≥ 15 points) on at least one IQ index and 26% on at least two indexes. Language, working memory, episodic memory, and executive functions were also significantly improved. Improvements were more pronounced in patients with a preoperative heterogeneous profile with isolated lower scores and a left-sided cyst. Parental questionnaires showed reduction in anxiety, aggressiveness, social problems, and daily life executive disorders. Preschool-aged children improved significantly in language and verbal IQ, as did middle/high school–aged children in many domains. Individual analyses revealed improvement in 76% of cases. Cognitive scores were lower for patients preoperatively than for controls and were no longer significantly different postoperatively in verbal fluency, visual memory, and working memory. Four years later, 97% of parents described an improvement in their child, correlated with cognitive improvements. CONCLUSIONS Among children with a TAC, some have no clinical signs or neuropsychological difficulties, and others may show signs of raised intracranial pressure and/or specific neuropsychological disorders that impact daily life and require significant and long-lasting rehabilitation. In these cases, consideration may be given to surgical decompression. It is interesting to note that 76% of this surgically treated cohort improved regardless of the child’s age, particularly in patients with selective disorders and an impact on daily life. However, a larger number of children will need to be investigated before the true benefit of such treatment can be known.

OBJECTIVE The aim of this study was to determine the cognitive profile of children with a temporal arachnoid cyst (TAC) and its impact on daily life. METHODS The authors prospectively analyzed the cognitive and psychological profiles of 100 consecutive children relative to age and cyst characteristics (side, cyst size, and cyst shape: convex or nonconvex) and their outcome 4 years later. RESULTS Mean IQs were normal but with high heterogeneity on Full Scale IQ (FSIQ; range 59–150); 29% of children had at least one Wechsler index below the norm, in particular, Processing Speed and Working Memory Indexes. Impairments were observed in language for 31% of children, as well as in verbal memory (28%), visual memory (23%), executive function (21%), and visual attention (24%). Half of the children (50%) needed rehabilitation for learning difficulties, and 26% had academic difficulties. The parental questionnaire BRIEF (Behavior Rating Inventory of Executive Function) revealed significant executive dysfunctions in daily life for 22% of the children. One-third of the patients (34%) required psychotherapy for anxiety or social disorders, with higher rates in patients with a right-sided cyst and older children. Cyst size had very little neuropsychological impact. Convex cysts were significantly associated with worse performance than nonconvex cysts on all Wechsler indexes and FSIQ, and in language, verbal memory, attention, and visuospatial skills. Children with a convex cyst had significantly more executive and behavior difficulties in daily life and more psychotherapy than other children. The effect of cyst shape was independent of Galassi type and cyst side. Children with a ruptured cyst or an incidentally discovered cyst usually had a good cognitive level. Four years later, children without initial disorders remained stable, whereas those with difficulties who did not undergo surgery needed more rehabilitation and school adaptations. CONCLUSIONS This large cohort study revealed a varied profile of children with a TAC: at initial assessment, 50% had neuropsychological difficulties and needed rehabilitation and/or psychotherapy for learning or behavior difficulties, and 50% had no difficulties, which may explain the debate about this pathology. Patients with neuropsychological difficulties had a heterogeneous profile with normal intelligence but selective cognitive and/or behavior disorders that may have a long-term impact on their quality of life, particularly those with a right-sided cyst. A neuropsychological evaluation is not always necessary for a cyst discovered incidentally, but early evaluation is essential in patients with academic, learning, or psychological disorders. When assessment shows selective disorders presumably linked to cyst location, surgery may be considered, particularly for convex cysts, as this study revealed more effects in association with cyst shape than with cyst size and significantly poorer performance with a convex cyst.

OBJECTIVE Rupture of brain arteriovenous malformation (AVM) is the main etiology of intracerebral hemorrhage (ICH) in children. Ensuing intracranial hypertension is among the modifiable prognosis factors and sometimes requires emergency hemorrhage evacuation (HE). The authors aimed to analyze variables associated with HE in children with ruptured AVM. METHODS This study was a single-center retrospective analysis of children treated for ruptured AVM. The authors evaluated the occurrence of HE, its association with other acute surgical procedures (e.g., nidal excision, decompressive hemicraniectomy), and clinical outcome. Variables associated with each intervention were analyzed using univariable and multivariable models. Clinical outcome was assessed at 18 months using the ordinal King’s Outcome Scale for Childhood Head Injury. RESULTS A total of 104 patients were treated for 112 episodes of ruptured AVM between 2002 and 2018. In the 51 children (45.5% of cases) who underwent HE, 37 procedures were performed early (i.e., within 24 hours after initial cerebral imaging) and 14 late. Determinants of HE were a lower initial Glasgow Coma Scale score (adjusted odds ratio [aOR] 0.83, 95% CI 0.71–0.97 per point increase); higher ICH/brain volume ratio (aOR 18.6, 95% CI 13–26.5 per percent increase); superficial AVM location; and the presence of a brain herniation (aOR 3.7, 95% CI 1.3–10.4). Concurrent nidal surgery was acutely performed in 69% of Spetzler-Martin grade I–II ruptured AVMs and in 25% of Spetzler-Martin grade III lesions. Factors associated with nidal surgery were superficial AVMs, late HE, and absent alteration of consciousness at presentation. Only 8 cases required additional surgery due to intracranial hypertension. At 18 months, overall mortality was less than 4%, 58% of patients had a favorable outcome regardless of surgical intervention, and 87% were functioning independently. CONCLUSIONS HE is a lifesaving procedure performed in approximately half of the children who suffer AVM rupture. The good overall outcome justifies intensive initial management.

OBJECTIVEUnderstanding the etiological spectrum of nontraumatic pediatric intracerebral hemorrhage (pICH) is key to the diagnostic workup and care pathway. The authors aimed to evaluate the etiological spectrum of diseases underlying pICH.METHODSChildren treated at the authors’ institution for a pICH were included in an inception cohort initiated in 2008 and retrospectively inclusive to 2000, which was analyzed in October 2019. They then conducted a systematic review of relevant articles in PubMed published between 1990 and 2019, identifying cohorts with pICH. Identified populations and patients from the authors’ cohort were pooled in a multicategory meta-analysis.RESULTSA total of 243 children with pICH were analyzed in the cohort study. The final primary diagnosis was an intracranial vascular lesion in 190 patients (78.2%), a complication of a cardiac disease in 17 (7.0%), and a coagulation disorder in 14 (5.8%). Hematological and cardiological etiologies were disproportionately more frequent in children younger than 2 years (p < 0.001). The systematic review identified 1309 children in 23 relevant records pooled in the meta-analysis. Overall, there was significant heterogeneity. The dominant etiology was vascular lesion, with an aggregate prevalence of 0.59 (95% CI 0.45–0.64; p < 0.001, Q = 302.8, I2 = 92%). In 18 studies reporting a detailed etiological spectrum, arteriovenous malformation was the dominant etiology (68.3% [95% CI 64.2%–70.9%] of all vascular causes), followed by cavernoma (15.7% [95% CI 13.0%–18.2%]).CONCLUSIONSThe most frequent etiology of pICH is brain arteriovenous malformation. The probability of an underlying vascular etiology increases with age, and, conversely, hematological and cardiac causes are dominant causes in children younger than 2 years.

A retrospective analysis of worker blood lead levels (BLL) was conducted using blood lead data collected by four bridge painting contractors before and after lead exposure. The objective of the study was to evaluate the effectiveness of exposure controls in preventing elevated blood lead levels (>25 μg/dl) during bridge painting projects. The contractors selected for the study submitted BLL data for 289 workers representing ten work tasks and 11 bridge painting projects. In total, 713 blood lead levels results were evaluated. The mean blood lead level for all work classifications combined was 10.9 μg/dl at baseline compared with 14.9 μg/dl after two months of exposure and 15.0 μg/dl after four months of exposure. Two months after initial exposure, 29% of the painters and 35% of the laborers had a 10 μg/dl incremental increase or greater in blood lead level. Likewise, 18% of the painters and 26% of the laborers had a blood lead level greater than 25 μg/dl during the same time. The blood lead levels that exceeded the 25 μg/dL threshold ranged from 30μg/dL-63 μg/dL for painters and 26 μg–56 μg/dL for laborers. All work tasks with high-intensity exposure (abrasive blaster/painter, abrasive blaster, painter & laborer) experienced an average blood lead level increase that ranged from 0.2 μg/dl to 8.9 μg/dl two months after initial exposure. Blood lead testing conducted after modified exposure controls (two months after the initial follow-up blood testing) were implemented showed a decrease in average blood lead levels (range −0.14 μg/dl to −2.7 μg/dl) for two high-intensity exposure work tasks. In comparison, the other two high-intensity work tasks had moderate increases (range 1 μg/dl to 2.4 μg/dl). The modified exposure controls included an increase in the air velocity inside of the work containment and an administrative control in the form of additional worker training on lead exposure prevention. The reduction in the 95th percentile (point estimate) BLL exposure profile for each exposure group at the 4-month follow-up blood testing period is associated with modified exposure controls. Ineffective exposure controls were identified through the analysis of worker BLLs. We found two exposure groups (laborer and painter) whose 95th percentile (point estimate) exposure profile was greater than the OSHA construction lead standard's targeted BLL goal (25 μg/dl) during the first two months of exposure. Our research findings provide support for monthly blood lead testing after baseline until blood lead levels are controlled to an acceptable concentration.

Poly(ADP-ribosyl)ation is an immediate cellular repair response to DNA damage and is catalyzed primarily by poly(ADP-ribose)polymerase-1 (PARP1), which is the most abundant of the 18 different PARP isoforms and accounts for more than 90% of the catalytic activity of PARP in the cell nucleus. Upon detection of a DNA strand break, PARP1 binds to the DNA, cleaves nicotinamide adenine dinucleotide between nicotinamide and ribose and then modifies the DNA nuclear acceptor proteins by formation of a bond between the protein and the ADP-ribose residue. This generates ribosyl-ribosyl linkages that act as a signal for other DNA-repairing enzymes and DNA base repair. Extensive DNA breakage in cells results in excessive activation of PARP with resultant depletion of the cellular stores of nicotinamide adenine dinucleotide (NAD+) which slows the rate of glycolysis, mitochondrial electron transport, and ultimately ATP formation in these cells. This paper focuses on PARP in DNA repair in atherosclerosis, acute myocardial infarction/reperfusion injury, and congestive heart failure and the role of PARP inhibitors in combating the effects of excessive PARP activation in these diseases. Free oxygen radicals and nitrogen radicals in arteries contribute to disruption of the vascular endothelial glycocalyx, which increase the permeability of the endothelium to inflammatory cells and also low-density lipoproteins and the accumulation of lipid in the vascular intima. Mild inflammation and DNA damage within vascular cells promote PARP1 activation and DNA repair. Moderate DNA damage induces caspase-dependent PARP cleavage and vascular cell apoptosis. Severe DNA damage due to vascular inflammation causes excessive activation of PARP1. This causes endothelial cell depletion of NAD+ and ATP, downregulation of atheroprotective SIRT1, necrotic cell death, and ultimately atherosclerotic plaque disruption. Inhibition of PARP decreases vascular endothelial cell adhesion P-selectin and ICAM-1 molecules, inflammatory cells, pro-death caspase-3, and c-Jun N-terminal kinase (JNK) activation and upregulates prosurvival extracellular signal-regulated kinases and AKT, which decrease vascular cell apoptosis and necrosis and limit atherosclerosis and plaque disruption. In myocardial infarction with coronary occlusion then reperfusion, which occurs with coronary angioplasty or thrombolytic therapy, reperfusion injury occurs in as many as 31% of patients and is caused by inflammatory cells, free oxygen and nitrogen radicals, the rapid transcriptional activation of inflammatory cytokines, and the activation of PARP1. Inhibition of PARP attenuates neutrophil infiltration and inflammatory cytokine expression in the reperfused myocardium and preserves myocardial NAD+ and ATP. In addition, PARP inhibition increases the activation of myocyte survival enzymes protein kinase B (Akt) and protein kinase C epsilon (PKCε), and decreases the activity of myocardial ventricular remodeling enzymes PKCα/β, PKCζ/λ, and PKCδ. As a consequence, cardiomyocyte and vascular endothelial cell necrosis is decreased and myocardial contractility is preserved. In heart failure and circulatory shock in animal models, PARP inhibition significantly attenuates decreases in left ventricular systolic pressure, ventricular contractility and relaxation, stroke volume, and increases survival by limiting or preventing upregulation of adhesion molecules, proinflammatory cytokines, myocardial mononuclear cell infiltration, and PKCα/β and PKC λ/ζ. In this manner, PARP inhibition partially restores the myocardial concentrations of NAD+, limits ventricular remodeling and fibrosis, and prevents significant decreases in myocardial contractility. Based primarily on investigations in preclinical models of atherosclerosis, myocardial infarction, and heart failure, PARP inhibition appears to be beneficial in limiting or inhibiting cardiovascular dysfunction. These studies indicate that investigations of acute and chronic PARP inhibition are warranted in patients with atherosclerotic coronary artery disease.

Background We report the surgical management of a lesional drug-resistant epilepsy caused by a meningioangiomatosis associated with a type IIIc focal cortical dysplasia located in the left supplementary motor area in a young male patient. Case Description A first anatomically based partial surgical resection was performed on an 11-year-old under general anesthesia without intraoperative mapping, which allowed for postoperative seizure control (Engel IA) for 6 years. The patient then exhibited intractable right sensatory and aphasic focal onset seizures despite 2 appropriate antiepileptic drugs. A second functional-based surgical resection was performed using intraoperative corticosubcortical functional mapping with direct electrical stimulation under awake conditions. A complete surgical resection was performed, and a left partial supplementary motor area syndrome was observed. At 6 months postoperatively, the patient is seizure free (Engel IA) with an ongoing decrease in antiepileptic drug therapy. Conclusions Intraoperative functional brain mapping can be applied to preserve the brain function and networks around a meningioangiomatosis to facilitate the resection of potentially epileptogenic perilesional dysplastic cortex and to tailor the extent of resection to functional boundaries.

Background Multiple burr hole (MBH) surgery is a simple, safe, and effective indirect technique of revascularization in moyamoya angiopathy (MM). However, it is not yet recognized as a first-line treatment. Objective To assess the long-term outcome and perioperative complications in a large single-center cohort of children with MM who underwent burr hole surgery. Methods This study is a retrospective analysis of children who underwent surgery for MM in a national reference center for pediatric stroke between 1999 and 2015. Sixty-four children (108 hemispheres, median age 7 years) were consecutively treated. The indication for revascularization was previous stroke or transient ischemic attack (TIA) or rapidly progressive disease on brain magnetic resonance imaging (MRI) and digital subtraction angiography. Children were followed with clinical examinations, telephone interviews, and MRI with any clinical recurrence of stroke or TIA used as the primary endpoint. Surgical mortality and morbidity were documented. Results Sixty-four patients were operated (bilateral MBH n = 39, unilateral procedure n = 25). At a mean follow-up of 4.2 years and 270.6 patient years, 89.1% of patients had not suffered any recurrent stroke or TIA. A second surgery was required in 5 cases after unilateral revascularization, and in 3 cases after bilateral MBH. Mortality associated with the procedure was 0. Postoperative Matsushima angiographic grading was the only predictive factor of ischemic recurrence ( P = .036). Conclusion In pediatric MM, MBH compares favorably to other indirect or direct revascularization techniques in children in the prevention of stroke or TIA.

Hemispherotomy is a treatment for drug-resistant epilepsy with the whole hemisphere involved in seizure onset. As recovery mechanisms are still debated, we characterize functional reorganization with multimodal MRI in two children operated on the right hemisphere (RH). We found that interhemispheric functional connectivity was abolished in both patients. The healthy left hemispheres (LH) displayed focal hyperperfusion in motor and limbic areas, and preserved network-level organization. The disconnected RHs were hypoperfused despite sustained network-level organization. Functional connectivity was increased in the left thalamo-cortical loop and between the cerebelli. The classification probability of the RH corresponding to a minimally conscious state was smaller than for the LH. We conclude that after hemispherotomy, neurological rehabilitation is sustained by cortical disinhibition and reinforcement of connectivity driven by subcortical structures in the remaining hemisphere. Our results highlight the effect of vascularization on functional connectivity and raise inquiries about the conscious state of the isolated hemisphere.

Background Right iliac fossa abdominal pain is a common reason for emergency ward admissions, its etiology is difficult to diagnose. It can be facilitated by an imaging examination, such as a Computerized Tomography scan which exposes the patient to ionizing radiation and implies delays. A bedside ultrasound performed by emergency physicians could avoid these issues. The aim of our study was to assess the performance of ultrasound carried out at the patient’s bedside by an emergency physician compared with a clinical-laboratory examination for the diagnosis of a surgical pathology in right iliac fossa pain. Methods This is a single-center prospective cohort study conducted in an Emergency Department receiving 19,000 patients per year. All patients presenting pain in the right iliac fossa were included by four (out of ten) emergency physicians certified in an ultrasound examination. A full grid pattern scan ultrasound of the abdominal cavity with analysis of the right iliac fossa was performed. The primary outcome was to compare the diagnosis performance of bedside ultrasound and clinical-laboratory examination to detect a surgical pathology. Two emergency physicians who did not participate in the study made the final diagnosis (i.e., surgical or non-surgical pathology) by reviewing the entire medical chart of each patient. Results From January 2011 to July 2013, 158 patients with a median age of 17 [13–32] years were analyzed. The diagnosed cases were: appendicitis (53), non-specific abdominal pain (48), lymphadenitis (22), ileitis (11), complicated ovarian cysts (7), neoplasias (5), inflammatory or infectious colitis (5), inguinal herniations (3), bowel obstructions (2), and salpingitis (2). The accuracy of ultrasound diagnoses was 0.89 (95% CI 0.84–0.94) versus 0.70 (95% CI 0.57–0.82) for diagnoses based on clinical-laboratory examination only (p

OBJECTIVEArachnoid cysts (ACs) are most frequently located in the middle cranial fossa. Some patients are asymptomatic whereas others exhibit signs of increased intracranial pressure, seizures, or cognitive and behavioral symptoms. When ACs do require treatment, the optimal surgical technique remains controversial. This study was conducted to assess the most effective surgical treatment for these cysts.METHODSThe authors retrospectively reviewed 240 temporal intracranial ACs managed over a 25-year period in their pediatric neurosurgical unit. Pre- and posttreatment results were clinically and radiologically assessed.RESULTSA majority of male patients (74.6%) with an overall median age of 6.9 years were included. The mean cyst size was 107 cm3; the Galassi classification showed 99 (41.3%) type I, 77 (32.1%) type II, and 64 (26.7%) type III cysts. Forty-four ACs (18.3%) were diagnosed after rupture. Surgical management was performed by microsurgery (28.3%), endoscopic cyst fenestration (14.6%), cystoperitoneal shunting (CPS; 16.2%), or subdural shunting (10%). Furthermore, 74 children (30.8%) did not undergo operations. After a mean follow-up of 4.1 years, the mean percentage decrease in cyst volume and the overall rate of clinical improvement did not significantly differ. The endoscopy group had earlier complications and a shorter event-free survival (EFS) time (EFS at 3 years = 67.7%, vs 71.5% and 90.5% for CPS and microsurgery, respectively; p < 0.007) and presented with more subdural hematomas compared to the microsurgery group (p < 0.005). The microsurgery group also showed a tendency for longer cystocisternostomy permeability than the endoscopy group.CONCLUSIONSConcerning the management of unruptured symptomatic temporal ACs, microsurgery appears to be the most effective treatment, with longer EFS and fewer complications compared to shunting or endoscopy.

Acrolein is a reactive electrophilic aldehyde known to cause mitochondrial dysfunction, oxidative stress, and dysregulation of signaling transduction in vitro. Most in vitro systems employ standard cell culture maintenance conditions of 95% air/5% CO

Although the association between hydrocephalus and epilepsy is well recognized, much controversy still exists about the incidence of epilepsy amongst hydrocephalic children. The reported occurrence varies from 6% to 59% in the literature [4, 6, 7, 12, 14, 16, 18, 22, 28–30, 36, 39, 41–>43]. There are many factors that may account for this, including the etiology of the hydrocephalus, its subsequent treatment and any resulting complications. A few studies indicate that the presence of a shunt [2, 13, 16, 26, 39], the number of shunt revisions [5, 6, 7, 13, 16, 28, 41], a history of shunt infection [2, 4, 5, 6, 16, 28, 39] and perhaps the shunt location [3, 7] increase the risk of developing seizures. However, long-term follow-up has rarely been provided and a number of important questions still remain unanswered. For example, the relationship between raised intracranial pressure and seizures and the way in which seizures in hydrocephalic children may affect developmental outcome have been poorly documented.

OBJECT Arterial spin labeling (ASL)-MRI is becoming a routinely used sequence for ischemic strokes, as it quantifies cerebral blood flow (CBF) without the need for contrast injection. As brain arteriovenous malformations (AVMs) are highflow vascular abnormalities, increased CBF can be identified inside the nidus or draining veins. The authors aimed to analyze the relevance of ASL-MRI in the diagnosis and follow-up of children with brain AVM. METHODS The authors performed a retrospective analysis of 21 patients who had undergone digital subtraction angiography (DSA) and pseudo-continuous ASL-MRI for the diagnosis or follow-up of brain AVM after radiosurgery or embolization. They compared the AVM nidus location between ASL-MRI and 3D contrast-enhanced T1 MRI, as well as the CBF values obtained in the nidus (CBFnidus) and the normal cortex (CBFcortex) before and after treatment. RESULTS The ASL-MRI correctly demonstrated the nidus location in all cases. Nidal perfusion (mean CBFnidus 137.7 ml/100 mg/min) was significantly higher than perfusion in the contralateral normal cortex (mean CBFcortex 58.6 ml/100 mg/min; p < 0.0001, Mann-Whitney test). Among 3 patients followed up after embolization, a reduction in both AVM size and CBF values was noted. Among 5 patients followed up after radiosurgery, a reduction in the nidus size was observed, whereas CBFnidus remained higher than CBFcortex. CONCLUSIONS In this study, ASL-MRI revealed nidus location and patency after treatment thanks to its ability to demonstrate focal increased CBF values. Absolute quantification of CBF values could be relevant in the follow-up of pediatric brain AVM after partial treatment, although this must be confirmed in larger prospective trials.

The aim was to localize the interictal cerebral perfusion abnormalities of focal cortical dysplasia (FCD) in children with Arterial Spin Labeling MRI (ASL) in a retrospective study of nine consecutive children explored with multimodal investigation during interictal periods. We analyzed brain morphology with a 1.5T MRI and a dedicated protocol for epilepsy. Brain perfusion was quantified with pseudo continuous ASL. Brain metabolism was imaged with (18)FDG-PET in six patients. Microvessel histology was studied in five children who underwent epilepsy surgery with CD34 immunostaining on FCD and control samples. Localized decrease of cerebral blood flow (CBF) was found on visual analysis in all patients with ASL. It was co-localized with the structural MRI abnormalities in every case, with PET hypo-metabolism in 5/6 cases, and with histologically proven FCD type IIb in 5/5 cases (all seizure free after surgery). CBF was lower (Kruskal-Wallis test, p=0.001) in FCD than in normal cortex. The total count of CD34+ microvessels was similar in FCD and control cases, but microvasculature showed disorganized architecture. Interictal ASL is a non-invasive method that may help to localize the epileptogenic zone showing hypo-perfusion in FCD. Whether this finding could be generalized to MRI-negative FCD needs to be further studied.

Purpose To propose and validate a modified pediatric intracerebral hemorrhage (PICH) (mPICH) score and to compare its association with functional outcome to that of the original PICH score. Materials and Methods Data from prospectively included patients were retrospectively analyzed. Consecutive patients with nontraumatic PICH who had undergone clinical follow-up were included. The study population was divided into a development cohort (2008-2012, n = 100) and a validation cohort (2013-2016, n = 43). An mPICH score was developed after variables associated with poor outcome were identified at multivariate analysis (King's Outcome Scale for Childhood Head Injury score5a) in the development cohort. The accuracy of the score for prediction of poor outcome was evaluated (sensitivity, specificity). Discrimination and calibration of associations between the mPICH score and poor outcome cohorts were assessed (C statistics, Hosmer-Lemeshow test). Results The mPICH score assessed as follows: brain herniation, four points; altered mental status, three points; hydrocephalus, two points; infratentorial PICH, two points; intraventricular hemorrhage, one point; PICH volume greater than 2% of total brain volume, one point. An mPICH score greater than 5 was associated with severe disability or worse, with sensitivity of 97% (95% confidence interval [CI]: 83%, 100%) and specificity of 61% (95% CI: 49%, 73%). The C statistic was 0.81 (95% CI: 0.73, 0.89). In the validation cohort, sensitivity and specificity were 95.2% (95% CI: 76%, 99%) and 77% (95% CI: 55%, 92%), respectively. There was no significant difference between the observed and predicted risks of poor outcome (P = .46). Conclusion An mPICH score was developed as a simple clinical and imaging grading scale for acute prognosis in patients with PICH.

Acrolein is a reactive α,β-unsaturated aldehyde known for its adduction to endogenous biomolecules, resulting in initiation or exacerbation of several disease pathways. In-vitro systems are routinely used to elucidate the cytotoxic or mechanistic role(s) of acrolein in pathogenesis. Nevertheless, the half-life of acrolein in biological or in-vitro systems, e.g. blood or culture media, has not been well characterized. Since in-vitro cytotoxic and mechanistic investigations routinely expose cultures to acrolein from 1 hour to 72 hours, we aimed to characterize the half-life of acrolein in culture medium to ascertain the plausible exposure window. Half-life determinations were conducted in low-serum DMEM at room temperature and 37 °C, both with and without H9c2 cells. For quantitative assessment, acrolein was derivatized to a fluorescent 7-hydroxyquinoline method validated in-house and assessed via fluorescent spectroscopy. In closed vessel experiments at room temperature, acrolein in DMEM was reduced by more than 40% at 24 hours, irrespective of the initial concentration. Expectedly, open vessel experiments demonstrated accelerated depletion over time at room temperature, and faster still at 37 °C. The presence of cells tended to further accelerate degradation by an additional 15-30%, depending on temperature. These results undermine described experimental exposure conditions stated in most in-vitro experiments. Recognition of this discrepancy between stated and actual exposure metrics warrant examination of novel alternative objective and representative exposure characterization for in-vitro studies to facilitate translation to in-vivo and in-silico methods.