White matter regions with low microstructure in young adults spatially coincide with white matter hyperintensities in older adults

Microstructural and macrostructural white matter damage occurs frequently with aging, is associated with negative health outcomes, and can be imaged non-invasively as fractional anisotropy (FA) and white matter hyperintensities (WMH), respectively. The extent to which diminished microstructure precedes or results from macrostructural white matter damage is poorly understood. This study evaluated the hypothesis that white matter areas with normatively lower microstructure in young adults are most susceptible to develop WMH in older adults. Forty-nine younger participants (age = 25.8 ± 2.8 years) underwent diffusion-weighted imaging (DWI), and 557 older participants (age = 73.9 ± 5.7 years) underwent DWI and T2-weighted magnetic resonance imaging (MRI). In older adults, WMH had a mostly periventricular distribution with higher frequency in frontal regions. We found lower FA in areas of frank WMH compared to normal-appearing white matter (NAWM) in older adults. Then, to determine if areas of normatively lower white matter microstructure spatially overlap with areas that frequently develop macrostructural damage in older age, we created a WMH frequency map in which each voxel represented the percentage of older adults with a WMH in that voxel. We found lower normative FA in young adults with regions frequently segmented as WMH in older adults. We conclude that low white matter microstructure is observed in areas of white matter macrostructural damage, but white matter microstructure is also normatively low (i.e., at ages 20–30) in regions with high WMH frequency, prior to white matter macrostructural damage

Relative contribution of white matter hyperintensity to amyloid and neurodegeneration in cognitive decline over time or clinical diagnoses in a diverse, community‐based cohort of older adults

Background: The 2018 NIA‐AA Alzheimer’s disease (AD) research framework moves towards a multiple biomarker approach to explain AD development and progression more fully. This research framework has the flexibility to incorporate various biomarkers into a full or partial amyloid‐tau‐neurodegeneration (A/T/N) profile. The objective of this study was to determine the relative contribution of white matter hyperintensities (WMH) to amyloid and neurodegeneration on cognition in a diverse, community‐based cohort of older adults. Method: A subset of cognitively healthy participants (n=155; age=69‐99yrs; 65% women, 30%/44%/26% Non‐Hispanic White/Non‐Hispanic Black/Hispanic) from the Washington Heights‐Inwood Columbia Aging Project underwent baseline Florbetaben PET (amyloid SUVR), T1‐weighted (cortical thickness[mm]) and T2‐weighted FLAIR MRI (WMH volume[cm3]), as well as subsequent neuropsychological assessments and consensus diagnoses every 1.5 years (up to 6 visits). Linear mixed effects models were used to test for change over time in language, memory, executive function, and visuospatial ability, while cox proportional hazard models were used to test for risk of developing MCI or AD. Biomarkers of interest included amyloid, cortical thickness, and WMH, adjusted for demographics (sex/gender, race/ethnicity, education). Interactions between biomarkers and time (e.g., slope differences) were evaluated as significant below 0.1. Result: In A/N/V models, higher amyloid was associated with faster rates of decline in language (B [95%CI]: ‐0.08 [‐0.13, ‐0.02]), memory (‐0.13 [‐0.21, ‐0.05]), and visuospatial ability (‐0.05 [‐0.12, 0.01]), higher WMH was associated with faster rates of decline in executive function (‐0.05 [‐0.11, 0.009]) and visuospatial ability (‐0.02 [‐0.05, 0.005]), and lower cortical thickness was associated with lower executive function scores (1.6 [0.10, 3.0]). Individuals were more likely to develop MCI or AD with higher amyloid (Hazard Ratio=4.2, [1.1, 15.9]), but not with higher WMH (1.2 [0.83, 1.7]) or lower cortical thickness (0.03 [4E‐4, 2]). Conclusion: In this imaging subsample of older community‐dwelling adults, cognitive decline is differentially associated by domain with amyloid or vascular burden, while broader, multi‐domain cognitive impairment necessary for MCI or AD diagnoses is associated with amyloid, one of the hallmark AD pathologies. Results support the use of complementary information from biomarker profiles, including traditional AD, vascular, and neurodegenerative biomarkers, to investigate AD and related dementias

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis

Childhood burns in south eastern Nigeria

Background: Burns injuries are recognized as a major health problem worldwide. In children and, particularly, in our environment where poverty, ignorance and disease are still high, they constitute significant morbidity and mortality. Previous studies on this topic in parts of Nigeria either lumped adults and children together or were retrospective. We, therefore, prospectively studied the current trends in burns in children. Patients and Methods: This prospective study of burns spanned over a period of 18 months (June 2006-December 2007) at the Paediatric Surgery Units of the Imo State University Teaching Hospital, Orlu, and the Federal Medical Centre, Owerri, Imo State. Data were collected and analysed for age, sex, cause/type of burn, place of burn, presence or absence of adult/s, initial prehospital intervention, interval between injury and presentation, surface area and depth of burn and treatment and outcome. Results: Fifty-three patients were studied, 31 (58.4%) were male and 22 (41.6%) were female (M:F = 1.4:1). Patients mostly affected were aged 2 years and below. The most common cause of burns was hot water in 31 (58.5%) patients. The vast majority of these injuries happened in a domestic environment (92.5%) and in the presence of competent adult/s (88.7%). Outcome of treatment was good: there were two (3.8%) deaths and 46 (86%) patients had complete recovery. Conclusion: Burns is still a major health problem among children in south eastern Nigeria. Fortunately, outcome of appropriate treatment is good. However, we think that poor safety consciousness among parents is a major predisposing factor. Public enlightenment on measures to ensure safe home environment may be necessary to avoid or limit childhood burns

Retrospective study of COVID-19 outcomes among healthcare workers in Rivers State, Nigeria

Objective To determine the illness severity and mortality among COVID-19-infected healthcare workers (HCWs). Design A retrospective cohort study using population-level data. Secondary analysis was conducted on collated data from the Public Health Emergency Operations Centre (PHEOC) at the State Ministry of Health, Rivers State, Nigeria. Data were gathered from the COVID-19 patient database of the PHEOC on demographics, place of work, illness severity and outcome. Participants The cohort included all documented HCWs with confirmed COVID-19 infection (diagnosed by PCR). Primary and secondary outcome measures Illness severity defined as \u27hospitalisation required\u27 and treatment outcome labelled as \u27alive\u27 or \u27dead\u27 were the outcomes of interest. Results The mean age was 43 years and 50.5% of the cohort were female. Of the 301 HCWs infected, 187 patients were symptomatic with 32 requiring hospitalisation. Seven infected HCWs died of their COVID-19 infection, resulting in a case fatality ratio (CFR) of 2.3%. Population proportions for age groups, case presentation and mortality, would be significantly greater than those seen in the study population. Health professionals made up 79.7% (240) of the study cohort, with 68.8% (165) of them working at the teaching hospitals; the association between HCWs and health facilities they worked in, was significant. Symptomatic cases were more inclined to progress to severe illness (χ(1)2=15.219,α=\u3c0.0001; adjusted OR (aOR) 10.658, 95% CI 2.494 to 45.552); patients also had greater odds of dying from COVID-19 (χ(5)2=13.7,α=0.003; aOR 1.079, 95% CI 1.02 to 1.141) per year increase in age adjusted for sex, case class and illness severity. Conclusions Frontl-ine HCWs are at an increased risk of exposure to COVID-19 infections. In Nigeria, there is a higher risk of experiencing severe illness if symptomatic while infected with COVID-19. Preventive strategies, proper education and awareness must be put in place to protect HCWs. Objective To determine the illness severity and mortality among COVID-19-infected HCWs

Spring active drain using bladder (50–60 ml) syringe (De Adotey’s drain)

Introduction: Closed active drainage system with a syringe is an accepted way to let out fluid in a surgical wound. We present a simple spring active (negative suction) drainage (SAD) system using locally improvised metallic spring and 60 ml (bladder syringe); SAD of Adotey, a newly designed compression–expansion spring mechanism which serves especially in situations where an active drainage system is of utmost importance. Conclusion: De Adotey's drain is a 60 ml bladder syringe with spring mechanism which is used to provide a negative pressure as an active drain

Ileosigmoid knotting in patients under 25 years of age: A report of two cases

INTRODUCTION: Ileosigmoid knotting is a rare cause of acute abdomen with high morbidity and mortality. Its diagnosis is infrequently made before surgery because of its varying ways of presentation and rarity. PRESENTATION OF CASE: The first was a 21-year-old male who presented with a history of sudden generalized abdominal pain and progressive abdominal distension. He was pale and severely dehydrated. His extremities were cold and clammy. His pulse rate was 110 per minute and blood pressure was 90/50 mmHg. The second case was 20-year-old male who presented with similar symptoms as above. He was not pale but mildly dehydrated. His pulse rate was 92 per minute and blood pressure 110/70 mmHg. Both patients were resuscitated and had exploratory laparotomy a few hours after presentation. The first patient was found to have ileosigmoid knotting with gangrenous sigmoid colon and terminal ileum. He had Hartmann's procedure and right hemicolectomy with ileo-transverse anastomosis. The second patient was found to have ileosigmoid knotting with viable loops of bowel. He had careful detorsion, sigmoidectomy with primary anastomosis. Both patients’ have good outcome. DISCUSSION: This is to report two cases of ileosigmoid knotting in two male patients aged 21 and 20 years, respectively, with the hope of increasing awareness. CONCLUSION: Ileosigmoid knotting though more common in fourth or fifth decade of life, can also occur in the 2nd decade. Early diagnosis, careful resuscitation and skilful surgical intervention will improve outcome

Automatic quantification of white matter hyperintensities on T2-weighted fluid attenuated inversion recovery magnetic resonance imaging

https://pubmed.ncbi.nlm.nih.gov/34662699/White matter hyperintensities (WMH) are areas of increased signal visualized on T2-weighted fluid attenuated inversion recovery (FLAIR) brain magnetic resonance imaging (MRI) sequences. They are typically attributed to small vessel cerebrovascular disease in the context of aging. Among older adults, WMH are associated with risk of cognitive decline and dementia, stroke, and various other health outcomes. There has been increasing interest in incorporating quantitative WMH measurement as outcomes in clinical trials, observational research, and clinical settings. Here, we present a novel, fully automated, unsupervised detection algorithm for WMH segmentation and quantification. The algorithm uses a robust preprocessing pipeline, including brain extraction and a sample-specific mask that incorporates spatial information for automatic false positive reduction, and a half Gaussian mixture model (HGMM). The method was evaluated in 24 participants with varying degrees of WMH (4.9-78.6 cm3) from a community-based study of aging and dementia with dice coefficient, sensitivity, specificity, correlation, and bias relative to the ground truth manual segmentation approach performed by two expert raters. Results were compared with those derived from commonly used available WMH segmentation packages, including SPM lesion probability algorithm (LPA), SPM lesion growing algorithm (LGA), and Brain Intensity AbNormality Classification Algorithm (BIANCA). The HGMM algorithm derived WMH values that had a dice score of 0.87, sensitivity of 0.89, and specificity of 0.99 compared to ground truth. White matter hyperintensity volumes derived with HGMM were strongly correlated with ground truth values (r = 0.97, p = 3.9e-16), with no observable bias (-1.1 [-2.6, 0.44], p-value = 0.16). Our novel algorithm uniquely uses a robust preprocessing pipeline and a half-Gaussian mixture model to segment WMH with high agreement with ground truth for large scale studies of brain aging

Regional white matter hyperintensities predict Alzheimer’s‐like neurodegeneration

BackgroundSmall vessel cerebrovascular disease, best visualized as white matter hyperintensities (WMH) on T2‐weighted MRI scanning, is associated with cognitive decline and increases risk for clinical Alzheimer’s disease (AD), particularly when it is distributed in posterior brain regions. There is much debate, however, about whether cerebrovascular disease represents a comorbidity or whether it is more fundamental to the pathogenesis of AD. The purpose of this study was to examine whether regional WMH volume predicts neurodegeneration, operationally‐defined as longitudinal decline in cortical thickness, among community‐dwelling older adults.MethodTwo hundred thirty‐eight participants(73.18+5.23 years old, 60% women, 35% APOE‐ε4 carriers, 30% non‐Hispanic White/32% Hispanic/38% Black, 14% with MCI) from the Washington Heights Inwood Columbia Aging Project (WHICAP) received high‐resolution structural 3T MRI scans at baseline and 4.09+1.57 years later. Regional WMH volume was derived with in house developed software and the FreeSurfer (v6.0) longitudinal processing stream was used to calculate change in cortical thickness. Using QDEC, we examined the relationship of total and regional WMH volume with annualized rate of decline in cortical thickness (symmetrized across the two visits) with vertex‐wise general linear models adjusted for age, sex, and APOE status. We additionally adjusted for a baseline marker of AD‐related atrophy (entorhinal cortex thickness).ResultBaseline total WMH volume predicted widespread cortical atrophy in a pattern consistent with AD‐associated atrophy, which included parahippocampal, temporal, and parietal regions. When examined regionally, the effects were most prominent for parietal lobe WMH, which predicted entorhinal cortex atrophy predominantly. Adjusting for baseline entorhinal cortical thickness did not alter the findings. In stratified analyses, the effects were strongest among Hispanic and Black participants compared with White participants, and similar across APOE groups.ConclusionWhite matter hyperintensity volume, especially in the parietal lobes, predicts Alzheimer’s‐like neurodegeneration, suggesting that small vessel cerebrovascular disease contributes to the ‘N’ aspect of the ‘A/T/N’ pathogenic models of AD. The results were independent of and stronger than baseline atrophy measures, suggesting that WMH are not simply a result of neurodegeneration. These effects may manifest differently across racial/ethnic groups, with small vessel cerebrovascular disease playing a more prominent role in future neurodegeneration among racial/ethnic minorities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163839/1/alz044776.pd