Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia.

BACKGROUND: Coronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti-interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear. METHODS: We randomly assigned (in a 2:1 ratio) patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. Site selection was focused on the inclusion of sites enrolling high-risk and minority populations. The primary outcome was mechanical ventilation or death by day 28. RESULTS: A total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group; 56.0% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native, 12.7% were non-Hispanic White, and 3.7% were of other or unknown race or ethnic group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P = 0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, -5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group. CONCLUSIONS: In hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified. (Funded by Genentech; EMPACTA ClinicalTrials.gov number, NCT04372186.).

Federal Food Assistance Accessibility and Acceptability Among Indigenous Peoples in the United States: A Scoping Review.

The purpose of this scoping review was to determine the extent to which accessibility and acceptability of federal food assistance programs in the United States have been evaluated among indigenous peoples and to summarize what is currently known. Twelve publications were found that examine aspects of accessibility or acceptability by indigenous peoples of 1 or more federal food assistance programs, including the supplemental nutrition assistance program (SNAP) and/or the Food Distribution Program on Indian Reservations (n = 8), the Special Supplemental Nutrition Program for Women, infants, and children (WIC) (n = 3), and the national school lunch program (n = 1). No publications were found to include the commodity supplemental food program or the child and adult care food program. Publications ranged in time from 1990-2023, and all reported on findings from rural populations, whereas 3 also included urban settings. Program accessibility varied by program type and geographic location. Road conditions, transportation access, telephone and internet connectivity, and an overall number of food stores were identified as key access barriers to SNAP and WIC benefit redemption in rural areas. Program acceptability was attributed to factors such as being tribally administered, providing culturally sensitive services, and offering foods of cultural significance. For these reasons, Food Distribution Program on Indian Reservations and WIC were more frequently described as acceptable compared to SNAP and national school lunch programs. However, SNAP was occasionally described as more acceptable than other assistance programs because it allows participants autonomy to decide which foods to purchase and when. Overall, little attention has been paid to the accessibility and acceptability of federal food assistance programs among indigenous peoples in the United States. More research is needed to understand and improve the participation experiences and health trajectories of these priority populations.

The E3 ubiquitin ligase Cul4b promotes CD4+ T cell expansion by aiding the repair of damaged DNA.

The capacity for T cells to become activated and clonally expand during pathogen invasion is pivotal for protective immunity. Our understanding of how T cell receptor (TCR) signaling prepares cells for this rapid expansion remains limited. Here we provide evidence that the E3 ubiquitin ligase Cullin-4b (Cul4b) regulates this process. The abundance of total and neddylated Cul4b increased following TCR stimulation. Disruption of Cul4b resulted in impaired proliferation and survival of activated T cells. Additionally, Cul4b-deficient CD4+ T cells accumulated DNA damage. In T cells, Cul4b preferentially associated with the substrate receptor DCAF1, and Cul4b and DCAF1 were found to interact with proteins that promote the sensing or repair of damaged DNA. While Cul4b-deficient CD4+ T cells showed evidence of DNA damage sensing, downstream phosphorylation of SMC1A did not occur. These findings reveal an essential role for Cul4b in promoting the repair of damaged DNA to allow survival and expansion of activated T cells.

GERD-screening before bariatric surgery: the predictive value of the GERD-HRQL questionnaire score compared with preoperative EGD findings.

BACKGROUND: There is an ongoing debate on how to best identify patients with gastroesophageal reflux disease (GERD) before bariatric surgery. The value of routine preoperative esophagogastroduodenoscopy (EGD) is questioned, and patient reported symptoms are commonly used for screening. The goal of this study is to determine if patient reported symptoms using a validated questionnaire correlate with preoperative EGD findings. METHODOLOGY: A prospective cohort study at a single institution was performed. Patients undergoing bariatric surgery between December 2020 and March 2023 were required to report symptoms of reflux by completing a preoperative GERD. Health-Related Quality of Life (GERD-HRQL) questionnaire and undergo a mandatory preoperative screening EGD. Patients were stratified into two cohorts: (group A) asymptomatic (score = 0) and (group B) symptomatic (score > 0). Statistical analysis was conducted using Pearson's chi-squared test and Wilcoxon rank-sum test in RStudio version 4.2.2. The predictive value of the GERD-HRQL score was analyzed using Areas Under the Curve (AUC; AUC = 0.5 not predictive, 0.5 < AUC ≥ 6 poor prediction & AUC > 0.9 excellent prediction) calculated from Receiver Operating Characteristic (ROC) curves. RESULTS: 200 patients were included; median age was 42.0 years (IQR 36.0 to 49.2). There were 79 patients (39.5%) in Group A and 121 patients (60.5%) in Group B. There was no difference in the frequency esophagitis (27.8% vs 32.2%, p = 0.61) or hiatal hernias (49.4% vs 47.1%, p = 0. 867) between group A and group B, respectively. ROC analysis revealed that the total GERD HRQL scores, heartburn only scores and regurgitation only scores, were poor predictors of esophagitis found on EGD (AUC 0.52, 0.53, 0.52), respectively. In asymptomatic patients, higher BMI was significantly associated with esophagitis (OR 1.15, 95% CI 1.06-1.27, p = 0.002). CONCLUSION: Symptoms, identified through the GERD-HRQL questionnaire, are a poor indicator of esophagitis or its severity in patients undergoing workup for bariatric surgery. Therefore, liberal screening upper endoscopy is recommended for pre-bariatric surgery patients to guide appropriate procedure selection.

Multimorbidity and its socio-economic associations in community-dwelling older adults in rural Tanzania; a cross-sectional study.

OBJECTIVES: This paper aims to describe the prevalence and socio-economic associations with multimorbidity, by both self-report and clinical assessment/screening methods in community-dwelling older people living in rural Tanzania. METHODS: A randomised frailty-weighted sample of non-institutionalised adults aged ≥ 60 years underwent comprehensive geriatric assessment and in-depth assessment. The comprehensive geriatric assessment consisted of a history and focused clinical examination. The in-depth assessment included standardised questionnaires, screening tools and blood pressure measurement. The prevalence of multimorbidity was calculated for self-report and non-self-reported methods (clinician diagnosis, screening tools and direct measurement). Multimorbidity was defined as having two or more conditions. The socio-demographic associations with multimorbidity were investigated by multiple logistic regression. RESULTS: A sample of 235 adults participated in the study, selected from a screened sample of 1207. The median age was 74 years (range 60 to 110 inter-quartile range (IQR) 19) and 136 (57.8%) were women. Adjusting for frailty-weighting, the prevalence of self-reported multimorbidity was 26.1% (95% CI 16.7-35.4), and by clinical assessment/screening was 67.3% (95% CI 57.0-77.5). Adjusting for age, sex, education and frailty status, multimorbidity by self-report increased the odds of being financially dependent on others threefold (OR 3.3 [95% CI 1.4-7.8]), and of a household member reducing their paid employment nearly fourfold (OR 3.8. [95% CI 1.5-9.2]). CONCLUSIONS: Multimorbidity is prevalent in this rural lower-income African setting and is associated with evidence of household financial strain. Multimorbidity prevalence is higher when not reliant on self-reported methods, revealing that many conditions are underdiagnosed and undertreated.

Treatment patterns in US patients hospitalized with COVID-19 and pulmonary involvement.

This study describes the baseline characteristics and treatment patterns of US patients hospitalized with a diagnosis of coronavirus disease 2019 (COVID-19) and pulmonary involvement. Patients hospitalized with pulmonary involvement due to COVID-19 (first hospitalization) were identified in the IBM Explorys® electronic health records database. Demographics, baseline clinical characteristics, and in-hospital medications were assessed. For evaluation of in-hospital medications, results were stratified by race, geographic region, age, and month of admission. Of 6564 hospitalized patients with COVID-19-related pulmonary involvement, 50.4% were male, and mean (SD) age was 62.6 (16.4) years; 75.2% and 23.6% of patients were from the South and Midwest, respectively, and 50.2% of patients were African American. Compared with African American patients, a numerically higher proportion of White patients received dexamethasone (19.7% vs. 31.8%, respectively), nonsteroidal anti-inflammatory drugs (NSAIDs; 27.1% vs. 34.9%), bronchodilators (19.8% vs. 29.5%), and remdesivir (9.3% vs. 21.0%). Numerically higher proportions of White patients than African American patients received select medications in the South but not in the Midwest. Compared with patients in the South, a numerically higher proportion of patients in the Midwest received dexamethasone (20.1% vs. 34.5%, respectively), NSAIDs (19.6% vs. 55.7%), bronchodilators (15.9% vs. 41.3%), and remdesivir (10.6% vs. 23.1%). Inpatient use of hydroxychloroquine decreased over time, whereas the use of dexamethasone and remdesivir increased over time. Among US patients predominantly from the South and Midwest hospitalized with COVID-19 and pulmonary involvement, differences were seen in medication use between different races, geographic regions, and months of hospitalization.

Rationing care by frailty during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic is disproportionately affecting older people and those with underlying comorbidities. Guidelines are needed to help clinicians make decisions regarding appropriate use of limited NHS critical care resources. In response to the pandemic, the National Institute for Health and Care Excellence published guidance that employs the Clinical Frailty Scale (CFS) in a decision-making flowchart to assist clinicians in assessing older individuals' suitability for critical care. This commentary raises some important limitations to this use of the CFS and cautions against the potential for unintended impacts. The COVID-19 pandemic has allowed the widespread implementation of the CFS with limited training or expert oversight. The CFS is primarily being used to assess older individuals' risk of adverse outcome in critical care, and to ration access to care on this basis. While some form of resource allocation strategy is necessary for emergencies, the implementation of this guideline in the absence of significant pressure on resources may reduce the likelihood of older people with frailty, who wish to be considered for critical care, being appropriately considered, and has the potential to reinforce the socio-economic gradient in health. Our incomplete understanding of this novel disease means that there is a need for research investigating the short-term predictive abilities of the CFS on critical care outcomes in COVID-19. Additionally, a review of the impact of stratifying older people by CFS score as a rationing strategy is necessary in order to assess its acceptability to older people as well as its potential for disparate impacts.

Tocilizumab for Severe and Critical COVID-19 Pneumonia in Queens, NYC.

New York City was hard hit by COVID-19. Elmhurst Hospital is a public hospital in Queens where more than 1500 patients were hospitalized with COVID. During the pandemic, various treatments were used with hopes of reducing the need for mechanical ventilation and death. METHODS: We retrospectively reviewed charts of patients admitted from March 25 to April 3 with severe or critical COVID-19 pneumonia who received tocilizumab compared with a similar cohort who did not. Analyses were performed to determine differences in outcomes. RESULTS: There was no observed difference in need for mechanical ventilation, length of stay, or mortality rate. In the tocilizumab-treated group, mechanical ventilation rate was 55%, and 49% of patients died. In the control group, 54% required mechanical ventilation and 46% died. Tocilizumab was overall well tolerated, although alanine aminotransferase elevation was more common in the tocilizumab-treated group. CONCLUSIONS: Tocilizumab failed to show short-term benefits in clinical outcomes in patients with hypoxic COVID pneumonia at our institution.

A brief frailty screening tool in Tanzania: external validation and refinement of the B-FIT screen.

BACKGROUND: Identifying older people who are most vulnerable to adverse outcomes is important. This is particularly so in low-resource settings, such as those in sub-Saharan Africa (SSA), where access to social and healthcare services is often limited. AIM: To validate and further refine a frailty screening tool for SSA. METHODS: Phase I screening of people aged 60 years and over was conducted using the Brief Frailty Instrument for Tanzania (B-FIT). In phase II, a stratified, frailty-weighed sample was assessed across a range of variables covering cognition, physical function (including continence, mobility, weakness and exhaustion) nutrition, mood, co-morbidity, sensory impairment, polypharmacy, social support and self-rated health. The frailty-weighted sample was also assessed for frailty according to the comprehensive geriatric assessment (CGA), which we used as our 'gold standard' diagnosis. RESULTS: Of 235 people in the frailty-weighted sample, 91 (38.7%) were frail according to CGA, the median age was 73 years and 136 (57.9%) were female. In multivariable modelling, physical disability (Barthel index), cognitive impairment (IDEA cognitive screen), calf circumference, poor distance vision and problems engaging in social activities were found to be associated with frailty. After developing a scoring system, based on regression coefficients, a modified B-FIT screen (B-FIT 2) had an area under the receiver operating characteristic curve of 0.925, a sensitivity of 86.2% and a specificity of 88.8%. DISCUSSION: The inclusion of items assessing nutrition, social support and sensory impairment improved the performance of the B-FIT. CONCLUSIONS: The B-FIT 2 should be externally validated.

Monitoring Walking Activity with Wearable Technology in Rural-dwelling Older Adults in Tanzania: A Feasibility Study Nested within a Frailty Prevalence Study.

BACKGROUND: Older adults with lower levels of activity can be at risk of poor health outcomes. Wearable technology has improved the acceptability and objectivity of measuring activity for older adults in high-income countries. Nevertheless, the technology is under-utilized in low-to-middle income countries. The aim was to explore feasibility, acceptability and utility of wearable technology to measure walking activity in rural-dwelling, older Tanzanians. METHODS: A total of 65 participants (73.9 ± 11.2 years), 36 non-frail and 29 frail, were assessed. Free-living data were recorded for 7 days with an accelerometer on the lower back. Data were analyzed via an automatic cloud-based pipeline: volume, pattern and variability of walking were extracted. Acceptability questionnaires were completed. T-tests were used for comparison between the groups. RESULTS: 59/65 datasets were analyzed. Questionnaires indicated that 15/65 (23.0%) experienced some therapeutic benefit from the accelerometer, 15/65 (23.0%) expected diagnostic benefit; 16/65 (24.6%) experienced symptoms while wearing the accelerometer (e.g. itching). Frail adults walked significantly less, had less variable walking patterns, and had a greater proportion of shorter walking bouts compared to the non-frail. CONCLUSION: This study suggests that important contextual and practical limitations withstanding wearable technology may be feasible for measuring walking activity in older rural-dwelling adults in low-income settings, identifying those with frailty.

The prevalence and characteristics of frailty by frailty phenotype in rural Tanzania.

BACKGROUND: The frailty phenotype is defined by the presence of three from the following five clinical features: weakness, slow walking speed, unintentional weight loss, exhaustion, and low physical activity. It has been widely applied in different research and clinical contexts, including across many low and middle-income countries. However, there is evidence that the operationalisation of each component of the frailty phenotype significantly alters its characteristics and predictive validity, and care is needed when applying the phenotype across settings. The study's objective was to operationalise the frailty phenotype in a rural Tanzanian population of older community-dwelling adults. METHODS: Consenting adults aged ≥60 years, and resident in five randomly selected villages of Hai district Demographic Surveillance Site, were eligible to participate in this cross-sectional study. From a screened sample of 1207 older adults, 235 were randomised and consented to an assessment of their frailty status by the frailty phenotype. Trained research fieldworkers (Tanzanian medical doctors and nurses) carried out measurements and questionnaires at local village centres or at participants' homes. RESULTS: The prevalence of the frailty phenotype, calculated from complete data for 196 participants, was 9.25% (95% CI 4.39-14.12) When missing data were counted as meeting frailty criterion (i.e. missing due to inability to perform an assessment), the prevalence increased to 11.22% (95% CI 7.11-15.32). Frailty by phenotype criteria was more common in older age groups, and was associated with self-assessed poor health and depression symptoms. CONCLUSIONS: Frailty can be successfully estimated using the frailty phenotype, however there are challenges in its operationalisation cross-culturally. Further work is needed to explore the potential clinical application of the frailty phenotype in such settings.

I Am Quite Mellow But I Wouldn't Say Everyone Else Is": How UK Students Compare Their Drinking Behavior to Their Peers'.

BACKGROUND: Excessive drinking is commonplace at UK Universities. Individuals may misperceive how much they drink compared to others and are less likely to think that they will suffer adverse consequences. Young people often distance themselves and their friends from 'problem drinkers'. OBJECTIVES: The aim of the study was to explore how student drinkers compared their own drinking behaviors to the drinking behaviors of others. METHODS: An online survey was completed by 416 students aged 18-30 (68.5% female). They were asked 'how do you think your drinking compares with other people like you?' and 'how do you think your behavior when you drink compares with other people like you?' Answers were subjected to thematic analysis. RESULTS: The first main theme was about 'identification as a 'good' drinker'. Participants suggested their own behavior when drinking was similar to their sober behavior. Further, they viewed themselves as more able to maintain a balance between staying in control and having fun while drinking. The second main theme was about 'distancing from being a 'bad' drinker. Participants distanced themselves from negative prototypical drinkers, such compulsive or anti-social drinkers. They also attributed their own drinking behaviors to situational factors, but described other people as intentionally violent or aggressive. Conclusions/Importance: These findings may explain the failure of some health messages to change drinking behaviors. If drinkers perceive that their behavior when they drink is better than other people's then they may discount intervention messages. Targeting these biases could be incorporated into future interventions.

Associations between outdoor fungal spores and childhood and adolescent asthma hospitalizations.

BACKGROUND: Childhood asthma is a significant public health problem and severe exacerbations can result in diminished quality of life and hospitalization. OBJECTIVE: We sought to examine the contribution of outdoor fungi to childhood and adolescent asthma hospitalizations. METHODS: The Melbourne Air Pollen Children and Adolescent study is a case-crossover study of 644 children and adolescents (aged 2-17 years) hospitalized for asthma. The Melbourne Air Pollen Children and Adolescent study collected individual data on human rhinovirus infection and sensitization to Alternaria and Cladosporium and daily counts of ambient concentrations of fungal spores, pollen, and air pollutants. Conditional logistic regression models were used to assess associations with increases in spore counts while controlling for potential confounding and testing interactions. RESULTS: Exposure to Alternaria (adjusted odds ratio [aOR], 1.07; 95% CI, 1.03-1.11), Leptosphaeria (aOR, 1.05; 95% CI, 1.02-1.07), Coprinus (aOR, 1.04; 95% CI, 1.01-1.07), Drechslera (aOR, 1.03; 95% CI, 1.00-1.05), and total spores (aOR, 1.05; 95% CI, 1.01-1.09) was significantly associated with child asthma hospitalizations independent of human rhinovirus infection. There were significant lagged effects up to 3 days with Alternaria, Leptosphaeria, Cladosporium, Sporormiella, Coprinus, and Drechslera. Some of these associations were significantly greater in participants with Cladosporium sensitization. CONCLUSIONS: Exposures to several outdoor fungal spore taxa, including some not reported in previous research, are associated with the risk of child and adolescent asthma hospitalization, particularly in individuals sensitized to Cladosporium. We need further studies to examine cross-reactivity causing asthma exacerbations. Identifying sensitization to multiple fungal allergens in children with asthma could support the design and implementation of more effective strategies to prevent asthma exacerbations.

Risk Factors for Delirium in Older Medical Inpatients in Tanzania.

BACKGROUND: The risk factors for prevalent delirium in older hospitalised adults in Sub-Saharan Africa (SSA) remain poorly characterised. METHODS: A total of 510 consecutive admissions of adults aged ≥60 years to acute medical wards of Kilimanjaro Christian Medical Centre in northern Tanzania were recruited. Patients were assessed within 24 h of admission with a risk factor questionnaire, physiological observations, neurocognitive assessment, and informant interview. Delirium and dementia diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM V) and DSM IV respectively, by an expert panel. RESULTS: Being male, current alcohol use, dementia, and physiological markers of illness severity were significant independent risk factors for delirium on multivariable analysis. CONCLUSIONS: The risk factors for prevalent delirium in older medical inpatients in SSA include pre-existing dementia, and are similar to those identified in high-income countries. Our data could help inform the development of a delirium risk stratification tool for older adults in SSA.

Aging with HIV in the ART era.

In the current era of therapy for human immunodeficiency virus (HIV), life expectancy for persons living with HIV (PLWH) approaches that of the general population. This newly prolonged survival among PLWH is associated with an increased prevalence of comorbidities due to the inflammation, immune activation and immune senescence associated with HIV infection. Higher prevalence of tobacco and alcohol use, co-infection with viral hepatitis and traditional cardiovascular risk factors such as hypertension and hyperlipidemia contribute as well. In this review, we hope to describe the current comorbidities occurring among PLWH and bring increased awareness for conditions that may otherwise not be considered given the younger age at time of presentation.

Atherosclerotic Cardiovascular Disease and Anti-Retroviral Therapy.

In the current era of available therapy for human immunodeficiency virus (HIV), life expectancy for persons living with HIV (PLWH) nears that of the general population. Atherosclerotic cardiovascular disease (ASCVD) has become a particular burden for PLWH and society at large. PLWH have historically been shown to have an excess of cardiovascular risk and subsequent events when compared to the general population. Potential explanations include the increased prevalence of traditional risk factors, direct inflammatory and immunological effects from the HIV virus itself, and metabolic adverse effects of anti-retroviral therapy (ART). Over the past few years, there has been building evidence that chronic inflammation and immune activation independent of virologic suppression contribute significantly to excess ASCVD risk. Although independent agents and combination therapies have varying metabolic effects, the evidence from major randomized controlled trials (RCTs) supports the benefits of early initiation of ART. In this review, we will discuss the epidemiology of ASCVD in HIV-infected patients compared with the general population, give an overview of potential pathogenesis of high-risk plaque in HIV-infected patients, discuss different metabolic effects of individual anti-retrovirals, and discuss the limitations in current screening models for assessing cardiovascular disease (CVD) risk and future directions for treatment.

Acute HCV in HIV-infected MSM: modes of acquisition, liver fibrosis, and treatment.

Hepatitis C virus (HCV) is not considered to be efficiently transmitted sexually, but since the early 2000s, HCV infection of HIV-infected men who have sex with men has emerged as an epidemic worldwide. In this review, we discuss the epidemiology of sexually transmitted acute HCV, the growing body of literature regarding risk factors for acquisition, and possible mechanisms of transmission. We also discuss the progression of liver disease in these men and the advances in therapy of acute HCV with interferon-free regimens and put forth our current approach of evaluating and treating these men in New York City.

The role of early intra-operative MRI in partial resection of optic pathway/hypothalamic gliomas in children.

INTRODUCTION: Optic pathway/hypothalamic gliomas (OPHGs) are generally benign but situated in an exquisitely sensitive brain region. They follow an unpredictable course and are usually impossible to resect completely. We present a case series of 10 patients who underwent surgery for OPHGs with the aid of intra-operative MRI (ioMRI). The impact of ioMRI on OPHG resection is presented, and a role for ioMRI in partial resection is discussed. METHODS: Ten patients with OPHGs managed surgically utilising ioMRI at Alder Hey Children's Hospital between 2010 and 2013 were retrospectively identified. Demographic and relevant clinical data were obtained. MRI was used to estimate tumour volume pre-operatively and post-resection. If ioMRI demonstrated that further resection was possible, second-look surgery, at the discretion of the operating surgeon, was performed, followed by post-operative imaging to establish the final status of resection. Tumour volume was estimated for each MR image using the MRIcron software package. RESULTS: Control of tumour progression was achieved in all patients. Seven patients had, on table, second-look surgery with significant further tumour resection following ioMRI without any surgically related mortality or morbidity. The median additional quantity of tumour removed following second-look surgery, as a percentage of the initial total volume, was 27.79% (range 11.2-59.2%). The final tumour volume remaining with second-look surgery was 23.96 vs. 33.21% without (p = 0.1). CONCLUSIONS: OPHGs are technically difficult to resect due to their eloquent location, making them suitable for debulking resection only. IoMRI allows surgical goals to be reassessed intra-operatively following primary resection. Second-look surgery can be performed if possible and necessary and allows significant quantities of extra tumour to be resected safely. Although the clinical significance of additional tumour resection is not yet clear, we suggest that ioMRI is a safe and useful additional tool, to be combined with advanced neuronavigation techniques for partial tumour resection.

Group B Streptococcus ß-hemolysin/cytolysin breaches maternal-fetal barriers to cause preterm birth and intrauterine fetal demise in vivo.

BACKGROUND: Maternal vaginal colonization with Streptococcus agalactiae (Group B Streptococcus [GBS]) is a precursor to chorioamnionitis, fetal infection, and neonatal sepsis, but the understanding of specific factors in the pathogenesis of ascending infection remains limited. METHODS: We used a new murine model to evaluate the contribution of the pore-forming GBS ß-hemolysin/cytolysin (ßH/C) to vaginal colonization, ascension, and fetal infection. RESULTS: Competition assays demonstrated a marked advantage to ßH/C-expressing GBS during colonization. Intrauterine fetal demise and/or preterm birth were observed in 54% of pregnant mice colonized with wild-type (WT) GBS and 0% of those colonized with the toxin-deficient cylE knockout strain, despite efficient colonization and ascension by both strains. Robust placental inflammation, disruption of maternal-fetal barriers, and fetal infection were more frequent in animals colonized with WT bacteria. Histopathologic examination revealed bacterial tropism for fetal lung and liver. CONCLUSIONS: Preterm birth and fetal demise are likely the direct result of toxin-induced damage and inflammation rather than differences in efficiency of ascension into the upper genital tract. These data demonstrate a distinct contribution of ßH/C to GBS chorioamnionitis and subsequent fetal infection in vivo and showcase a model for this most proximal step in GBS pathogenesis.

Disentangling Alcohol-Related Needs Among Pre-trial Prisoners: A Longitudinal Study.

AIMS: To disentangle the alcohol-related needs of short stay, revolving door, male prisoners, and offer a theoretically driven but practical approach for allocation of scarce service resources. METHODS: A prospective longitudinal interview, questionnaire and records study of pre-trial men newly imprisoned in Wales and SW England. RESULTS: Two hundred and forty-one pre-trial men completed an interview and questionnaires within a week of a new reception into prison; 170 completed follow-up 3 weeks later. Questions about problems with alcohol or illicit drugs revealed that problem drinkers were less likely than problem drug users to recognize their difficulty or seek or get help for this during their first month of imprisonment. Co-morbidity was common, but a third of the men had alcohol problems alone. Use of the Alcohol Use Disorders Identification Test (AUDIT) questionnaire identified 80% (195/241) men likely to require some intervention, twice the number identified by direct questions relying on prisoners' judgment about problem use. Furthermore it allowed categorization according to likely risk (dependency), need (problem recognition) and responsivity (wish for help). CONCLUSION: Alcohol misuse is recognized, worldwide, as fuelling crime and more common among prisoners than the general population. In England and Wales, it is a particular factor in brief but recurrent periods of imprisonment. There have been calls to pay more attention to its use in this context, albeit without any increase in resources. Adding two questions to standard screening enables application of the risk-need-responsivity model to problem drinkers and may identify those most likely to benefit from treatment.