Cardiac magnetic resonance predictors for successful primary biventricular repair of unbalanced complete common atrioventricular canal.

BACKGROUND: Patients with unbalanced common atrioventricular canal can be difficult to manage. Surgical planning often depends on pre-operative echocardiographic measurements. We aimed to determine the added utility of cardiac MRI in predicting successful biventricular repair in common atrioventricular canal. METHODS: We conducted a retrospective cohort study of children with common atrioventricular canal who underwent MRI prior to repair. Associations between MRI and echocardiographic measures and surgical outcome were tested using logistic regression, and models were compared using area under the receiver operator characteristic curve. RESULTS: We included 28 patients (median age at MRI: 5.2 months). The optimal MRI model included the novel end-diastolic volume index (using the ratio of left ventricular end-diastolic volume to total end-diastolic volume) and the left ventricle-right ventricle angle in diastole (area under the curve 0.83, p = 0.041). End-diastolic volume index ≤ 0.18 and left ventricle-right ventricle angle in diastole ≤ 72° yield a sensitivity of 83% and specificity of 81% for successful biventricular repair. The optimal multimodality model included the end-diastolic volume index and the echocardiographic atrioventricular valve index with an area under the curve of 0.87 (p = 0.026). CONCLUSIONS: Cardiac MRI can successfully predict successful biventricular repair in patients with unbalanced common atrioventricular canal utilising the end-diastolic volume index alone or in combination with the MRI left ventricle-right ventricle angle in diastole or the echocardiographic atrioventricular valve index. A prospective cardiac MRI study is warranted to better define the multimodality characteristic predictive of successful biventricular surgery.

Reduction in Substance-Related Composite Harm Scores Through Street Soccer.

Introduction Street soccer makes the sport accessible to people affected by homelessness or precarious housing. There is overwhelming evidence that exercise improves physical and mental health. In addition, sport facilitates positive peer pressure that leads to beneficial life changes. Method To examine participants' accounts of the effects of street soccer in a sample of socially disadvantaged players from Western Canada, we collected 73 cross-sectional self-reports of life changes via a questionnaire. The questionnaire included questions on social, mental, and physical health, including substance use. This allowed the calculation of a modified composite harm score. Results Participants reported improved physical (46% of participants) and mental (43% of participants) health, reduced cigarette (50% of smokers), alcohol (45% of users), cannabis (42% of users), and other non-prescribed drug use, increased number of friends (88% of participants), improved housing (60% of participants), increased income (19% of participants), increased community medical supports (40% of participants), and decreased conflicts with police (47% of those with prior recent conflict). Perceived reductions in substance use were supported by significant changes in composite harm score. Conclusion Street soccer appears to promote improved physical, mental, and social health among people affected by homelessness or precarious housing, with reduction in substance use likely to be a key factor. This work builds upon past qualitative research showing the benefits of street soccer and supports future research which may help elucidate the mechanisms by which street soccer has beneficial effects.

Biomarkers, Socioeconomic Factors, and Right Ventricular Function After Surgical Repair for Tetralogy of Fallot.

Right ventricular (RV) dysfunction early after tetralogy of Fallot (TOF) increases post-operative morbidity. We investigated associations of circulating biomarkers and socioeconomic factors with early post-operative RV systolic function. Single-center prospective cohort study of infants undergoing TOF repair. Six serologic biomarkers of myocardial fibrosis and wall stress collected at the time of surgery were measured with immunoassay. Geocoding was performed for socioeconomic factors. Multivariate adaptive regression splines (MARS) models identified factors associated with RV function parameters: fractional area change (FAC), global longitudinal strain and strain rate, and free wall strain and strain rate. Seventy-one patients aged 3.5 months (IQR 2.4, 5.2) were included. Galectin-3 was the highest ranked predictor for FAC, global longitudinal strain, and free wall strain, and procollagen type-I carboxy-terminal propeptide (PICP) was the highest ranked predictor for global longitudinal strain rate and free wall strain rate. Several neighborhood characteristics were also highly ranked. Models adjusted R2 ranged from 0.71 to 0.85 (FAC, global longitudinal strain/strain rate), and 0.55-0.57 (RV free wall strain/strain rate). A combination of serologic biomarkers, socioeconomic, and clinical variables explain a significant proportion of the variability in RV function after TOF repair. These factors may inform pre-operative risk-stratification for these patients.

Participatory peer research exploring the experience of learning during Covid-19 for allied health and healthcare science students.

INTRODUCTION: The teaching and learning experience of allied health and healthcare science students has altered because of the Covid-19 pandemic. Limited research has explored the experience on the future healthcare workforce using participatory research design. The aim of this study was to explore the impact of a global pandemic on the clinical and academic experiences of healthcare student using a co-production approach with student peer researchers. METHODS: A participatory research approach adopting online focus groups facilitated by students trained as peer researchers was adopted. First, second and final year students from occupational therapy, physiotherapy, podiatry, healthcare science, diagnostic radiography and imaging, radiotherapy and oncology, and speech and language therapy were recruited to six focus groups. Data generated through focus groups were analysed thematically using the DEPICT model to support a partnership approach. RESULTS: Twenty-three participants took part in six focus groups. The themes identified were: rapid changes to learning; living alongside Covid-19 and psychological impact. Students preferred blended learning approaches when available, as reduced peer interaction, studying and sleeping in the same space, and technology fatigue decreased motivation. CONCLUSION: Due to rapid changes in learning and the stress, anxiety and isolation created by the pandemic, managing study, personal life and placement resulted in a gap in confidence in clinical skills development for students. Students took their professional identity seriously, engaged in behaviours to reduce transmission of Covid-19 and employed a range of coping strategies to protect wellbeing. A challenge with the move to online delivery was the absence of informal peer learning and students indicated that moving forward they would value a hybrid approach to delivery. Higher Education should capitalise on innovative learning experiences developed during the pandemic however it is important to research the impact this has on student skill acquisition and learning experience.

Cellular heterogeneity of human fallopian tubes in normal and hydrosalpinx disease states identified using scRNA-seq.

Fallopian tube (FT) homeostasis requires dynamic regulation of heterogeneous cell populations and is disrupted in infertility and ovarian cancer. Here, we applied single-cell RNA-seq to profile 59,738 FT cells from four healthy, pre-menopausal subjects. The resulting cell atlas contains 12 major cell types representing epithelial, stromal, and immune compartments. Re-clustering of epithelial cells identified four ciliated and six non-ciliated secretory epithelial subtypes, two of which represent potential progenitor pools: one leading to mature secretory cells and the other contributing to either ciliated cells or one of the stromal cell types. To understand how FT cell numbers and states change in a disease state, we analyzed 17,798 cells from two hydrosalpinx samples and observed shifts in epithelial and stromal populations and cell-type-specific changes in extracellular matrix and TGF-ß signaling; this underscores fibrosis pathophysiology. This resource is expected to facilitate future studies aimed at expanding understanding of fallopian tube homeostasis in normal development and disease.

Delayed Opsoclonus-Myoclonus Syndrome After Ovarian Teratoma Resection.

ABSTRACT: Opsoclonus-myoclonus syndrome (OMS) is a rare syndrome characterized by opsoclonus, which is irregular, spontaneous, multivectorial saccadic eye movements, along with diffuse or focal myoclonus and sometimes ataxia. OMS is associated with paraneoplastic etiologies in 20%-40% of cases, with small-cell lung and breast cancers the most common associated primary neoplasms in adults, whereas neuroblastoma is more common in children and ovarian teratoma may occur in women younger than 30 years. Onconeural antibodies are often not identified. In existing literature, paraneoplastic OMS precedes identification of the neoplasm, and neurological recovery depends on treatment of the underlying cancer. We describe a 27-year-old woman with the delayed onset of OMS one month after resection of ovarian teratoma, likely due to immune trigger from antigen exposure at the time of resection. She was treated with intravenous methylprednisolone, immunoglobulins, and eventually rituximab with resolution of her symptoms. Identification of OMS after tumor resection and prompt immunotherapy are critical for neurologic recovery. At 30-month follow-up, this patient had not experienced recurrence of OMS.

Capitalizing on transcriptome profiling to optimize and identify targets for promoting early murine folliculogenesis in vitro.

In vitro ovarian follicle culture is an active area of research towards providing fertility options for survivors of childhood cancer. Late-stage murine follicles (multilayer secondary and onwards) can be cultured successfully to maturity to obtain a meiotically competent oocyte for fertilization, but primordial and primary follicles usually die in culture because many key components of early follicle development are still unknown and difficult to mimic in vitro. To engineer a biomimetic three-dimensional culture system with high efficacy and reproducibility for the clinic, detailed mechanisms of early folliculogenesis must be uncovered. Previous studies have shown that primary murine follicles co-cultured in groups, in contrast to single follicles cultured in isolation, can reach preovulatory size and produce competent oocytes, but the factors accounting for the synergy of follicle co-culture are still unknown. To probe the underlying mechanisms of successful follicle co-culture, we conducted a time-course experiment for murine follicles encapsulated in 0.3% alginate hydrogels and compared between two conditions: groups of 5 (5X) versus groups of 10 (10X). For every 2 days during the course of 12 days, follicles were dissociated and somatic cells were isolated for microarray-based gene expression analysis (n = 380 follicles for 5X and n = 430 follicles for 10X). Gene activities in follicles co-cultured in larger groups (10X) had a distinct transcriptomic profile of key genes and pathways such as prolactin signaling and angiogenesis-related genes when compared to cells from follicles co-cultured in the smaller cohort (5X). To benchmark the results for follicles grown in culture, we compared our microarray data to data from murine follicles freshly isolated from the ovary at comparable stages of development previously published by Bernabé et al. Comparison of these datasets identified similarities and differences between folliculogenesis in the native microenvironment and the engineered in vitro system. A more detailed understanding of follicle growth in vitro will not only allow for better culture methods but also advance the field towards providing improved fertility options for survivors of childhood cancer.

Ki-67 "hot spot" digital analysis is useful in the distinction of hepatic adenomas and well-differentiated hepatocellular carcinomas.

This study aims to investigate the utility of digital protocols for Ki-67 immunohistochemistry quantitative analysis ("hot spot" method) in the setting of well-differentiated hepatocellular neoplasms. Resection cases of typical hepatic adenomas (HAs) (n = 40), atypical HAs (n = 9), and well-differentiated hepatocellular carcinomas (WD HCCs) (n = 56) were selected. HAs were further classified by immunohistochemistry using antibodies against liver fatty acid binding protein, glutamine synthetase, B-catenin, hepatic serum amyloid A, and C-reactive protein. Ki-67 proliferative index by immunohistochemistry was evaluated in all cases by digital analysis using a modified neuroendocrine tumor "hot spot" protocol. The proliferative rate of HAs (typical, median 1.2% (range 0-7.4%) and atypical, median 1.0% (range 0.3-3%)) was significantly lower than that of WD HCCs (median 4.5%, range 0-49.8%) (P < 0.0001). Only a few (7.5%) of the adenomas (all inflammatory/telangiectatic type) had proliferative rates higher than 4%, compared to most (51%) of HCCs. Ki-67 is a potentially useful adjunct marker in the evaluation of WD hepatocellular neoplasms, as "hot spot" proliferative rates are consistently very low in HAs but vary significantly in WD HCCs.

Cerebral Small Vessel Disease, Risk Factors, and Cognition in Tenants of Precarious Housing.

BACKGROUND AND PURPOSE: We aim to describe the burden, characteristics, and cognitive associations of cerebral small vessel disease in a Canadian sample living with multimorbidity in precarious housing. METHODS: Participants received T1, T2-fluid-attenuated inversion recovery, and susceptibility-weighted imaging 3T magnetic resonance imaging sequences and comprehensive clinical, laboratory, and cognitive assessments. Cerebral small vessel disease burden was characterized using a modified Small Vessel Disease (mSVD) score. One point each was given for moderate-severe white matter hyperintensities, ≥1 cerebral microbleeds, and ≥1 lacune. Multivariable regression explored associations between mSVD score, risk factors, and cognitive performance. RESULTS: Median age of the 228 participants (77% male) was 44.7 years (range, 23.3-63.2). In n=188 participants with consistent good quality magnetic resonance imaging sequences, mSVD scores were 0 (n=127, 68%), 1 (n=50, 27%), and 2 (n=11, 6%). Overall, one-third had an mSVD ≥1 n=61 (32%); this proportion was unchanged when adding participants with missing sequences n=72/228 (32%). The most prevalent feature was white matter hyperintensities 53/218 (24%) then cerebral microbleed 16/191 (8%) and lacunes 16/228 (7%). Older age (odds ratio, 1.10 [95% CI, 1.05-1.15], P<0.001), higher diastolic blood pressure (odds ratio, 1.05 [95% CI, 1.01-1.09], P=0.008), and a history of injection drug use (odds ratio, 3.13 [95% CI, 1.07-9.16], P=0.037) had significant independent associations with a mSVD score of ≥1 in multivariable analysis. mSVD ≥1 was associated with lower performance on tests of verbal memory, sustained attention, and decision-making, contributing 4% to 5% of the variance in each cognitive domain. CONCLUSIONS: The 32% prevalence of cerebral small vessel disease in this young, socially marginalized cohort was higher than expected for age and was associated with poorer cognitive performance.

Associations of substance use, psychosis, and mortality among people living in precarious housing or homelessness: A longitudinal, community-based study in Vancouver, Canada.

BACKGROUND: The "trimorbidity" of substance use disorder and mental and physical illness is associated with living in precarious housing or homelessness. The extent to which substance use increases risk of psychosis and both contribute to mortality needs investigation in longitudinal studies. METHODS AND FINDINGS: A community-based sample of 437 adults (330 men, mean [SD] age 40.6 [11.2] years) living in Vancouver, Canada, completed baseline assessments between November 2008 and October 2015. Follow-up was monthly for a median 6.3 years (interquartile range 3.1-8.6). Use of tobacco, alcohol, cannabis, cocaine, methamphetamine, and opioids was assessed by interview and urine drug screen; severity of psychosis was also assessed. Mortality (up to November 15, 2018) was assessed from coroner's reports and hospital records. Using data from monthly visits (mean 9.8, SD 3.6) over the first year after study entry, mixed-effects logistic regression analysis examined relationships between risk factors and psychotic features. A past history of psychotic disorder was common (60.9%). Nonprescribed substance use included tobacco (89.0%), alcohol (77.5%), cocaine (73.2%), cannabis (72.8%), opioids (51.0%), and methamphetamine (46.5%). During the same year, 79.3% of participants reported psychotic features at least once. Greater risk was associated with number of days using methamphetamine (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.05-1.24, p = 0.001), alcohol (aOR 1.09, 95% CI 1.01-1.18, p = 0.04), and cannabis (aOR 1.08, 95% CI 1.02-1.14, p = 0.008), adjusted for demographic factors and history of past psychotic disorder. Greater exposure to concurrent month trauma was associated with increased odds of psychosis (adjusted model aOR 1.54, 95% CI 1.19-2.00, p = 0.001). There was no evidence for interactions or reverse associations between psychotic features and time-varying risk factors. During 2,481 total person years of observation, 79 participants died (18.1%). Causes of death were physical illness (40.5%), accidental overdose (35.4%), trauma (5.1%), suicide (1.3%), and unknown (17.7%). A multivariable Cox proportional hazard model indicated baseline alcohol dependence (adjusted hazard ratio [aHR] 1.83, 95% CI 1.09-3.07, p = 0.02), and evidence of hepatic fibrosis (aHR 1.81, 95% CI 1.08-3.03, p = 0.02) were risk factors for mortality. Among those under age 55 years, a history of a psychotic disorder was a risk factor for mortality (aHR 2.38, 95% CI 1.03-5.51, p = 0.04, adjusted for alcohol dependence at baseline, human immunodeficiency virus [HIV], and hepatic fibrosis). The primary study limitation concerns generalizability: conclusions from a community-based, diagnostically heterogeneous sample may not apply to specific diagnostic groups in a clinical setting. Because one-third of participants grew up in foster care or were adopted, useful family history information was not obtainable. CONCLUSIONS: In this study, we found methamphetamine, alcohol, and cannabis use were associated with higher risk for psychotic features, as were a past history of psychotic disorder, and experiencing traumatic events. We found that alcohol dependence, hepatic fibrosis, and, only among participants <55 years of age, history of a psychotic disorder were associated with greater risk for mortality. Modifiable risk factors in people living in precarious housing or homelessness can be a focus for interventions.

Gender Differences in Surgery for Work-Related Musculoskeletal Injury: A Population-Based Cohort Study.

OBJECTIVE: The objective of this study is to examine if women are less likely than men to receive surgery following work-related musculoskeletal injury in the Canadian province of British Columbia. METHODS: The study included 2,403 workers with work-related knee meniscal tear, thoracic/lumbar disc displacement or rotator cuff tear. Probability of surgery was compared by gender using Kaplan-Meier methods and Cox proportional hazards models. RESULTS: For each injury type, a smaller proportion of women received surgery compared to men (knee: 76% vs. 80%; shoulder: 13% vs. 36%; back: 13% vs. 19%). In adjusted models, compared to men, women were 0.87 (95% confidence interval [CI] [0.69, 1.09]), 0.35 (95% CI [0.25, 0.48]) and 0.54 (95% CI [0.31, 0.95]) times less likely to receive knee, shoulder or back surgery, respectively. CONCLUSIONS: Probability of surgery following work-related musculoskeletal injury was lower for women than for men. Strategies to ensure gender equitable delivery of surgical services by workers' compensation systems may be warranted, although further research is necessary to investigate determinants of the gender difference and the impact of elective orthopaedic surgery on occupational outcomes.

Ovarian tissue cryopreservation and novel bioengineering approaches for fertility preservation.

PURPOSE OF REVIEW: Breast cancer patients who cannot delay treatment or for whom hormone stimulation and egg retrieval are contraindicated require alternative methods of fertility preservation prior to gonadotoxic treatment. Ovarian tissue cryopreservation is an alternative approach that may offer patients the opportunity to preserve fertility and carry biologically-related children later in life. Various experimental approaches are being explored to obtain mature gametes from cryopreserved and thawed ovarian tissue for fertilization and implantation using biomimetic tissue culture in vitro. Here we review the most recent developments in ovarian tissue cryopreservation and exciting advances in bioengineering approaches to in vitro tissue and ovarian follicle culture. RECENT FINDINGS: Slow freezing is the most widely accepted method for ovarian tissue cryopreservation, but efforts have been made to modify vitrification for this application as well. Numerous approaches to in vitro tissue and follicle culture are in development, most prominently two-step culture systems for ovarian cortical tissue and encapsulation of ovarian follicles in biomimetic matrices for in vitro culture. SUMMARY: Refinements to slow freeze and vitrification protocols continue to address challenges associated with cryopreservation, such as ice crystal formation and damage to the stroma. Similarly, improvements to in vitro tissue and follicle culture show promise for utilizing patients' cryopreserved tissues to obtain mature gametes after disease treatment and remission. Development of an effective and reproducible culture system for human ovarian follicles will serve as a broad assisted reproductive technology for cancer survivors who cryopreserved tissue prior to treatment.

Social and structural factors associated with substance use within the support network of adults living in precarious housing in a socially marginalized neighborhood of Vancouver, Canada.

BACKGROUND: The structure of a social network as well as peer behaviours are thought to affect personal substance use. Where substance use may create health risks, understanding the contribution of social networks to substance use may be valuable for the design and implementation of harm reduction or other interventions. We examined the social support network of people living in precarious housing in a socially marginalized neighborhood of Vancouver, and analysed associations between social network structure, personal substance use, and supporters' substance use. METHODS: An ongoing, longitudinal study recruited 246 participants from four single room occupancy hotels, with 201 providing social network information aligned with a 6-month observation period. Use of tobacco, alcohol, cannabis, cocaine (crack and powder), methamphetamine, and heroin was recorded at monthly visits. Ego- and graph-level measures were calculated; the dispersion and prevalence of substances in the network was described. Logistic mixed effects models were used to estimate the association between ego substance use and peer substance use. Permutation analysis was done to test for randomness of substance use dispersion on the social network. RESULTS: The network topology corresponded to residence (Hotel) with two clusters differing in demographic characteristics (Cluster 1 -Hotel A: 94% of members, Cluster 2 -Hotel B: 95% of members). Dispersion of substance use across the network demonstrated differences according to network topology and specific substance. Methamphetamine use (overall 12%) was almost entirely limited to Cluster 1, and absent from Cluster 2. Different patterns were observed for other substances. Overall, ego substance use did not differ over the six-month period of observation. Ego heroin, cannabis, or crack cocaine use was associated with alter use of the same substances. Ego methamphetamine, powder cocaine, or alcohol use was not associated with alter use, with the exception for methamphetamine in a densely using part of the network. For alters using multiple substances, cannabis use was associated with lower ego heroin use, and lower ego crack cocaine use. Permutation analysis also provided evidence that dispersion of substance use, and the association between ego and alter use was not random for all substances. CONCLUSIONS: In a socially marginalized neighborhood, social network topology was strongly influenced by residence, and in turn was associated with type(s) of substance use. Associations between personal use and supporter's use of a substance differed across substances. These complex associations may merit consideration in the design of interventions to reduce risk and harms associated with substance use in people living in precarious housing.

Prevalence and Risk Factors of Brain Infarcts and Associations With Cognitive Performance in Tenants of Marginal Housing.

Background Homeless and vulnerably housed individuals are at increased risk for multimorbidity compared with the general population. We assessed prevalence of brain infarcts on neuroimaging and associations with vascular risk factors and cognitive performance in a prospective study of residents living in marginal housing. Methods and Results Two hundred twenty-eight participants underwent structured clinical interviews, targeted clinical, laboratory, and neuropsychological assessments, and magnetic resonance imaging with T1, T2-fluid-attenuated inversion recovery and susceptibility-weighted images. Subjects underwent cognitive testing to assess premorbid IQ , verbal learning and memory, inhibition, sustained attention, mental flexibility, and decision making. In this sample (mean age 44.0 years [ SD 9.4], 77% male), prevalence of conventional vascular risk factors was lower than in the general population apart from tobacco use (94%). Ten-year Framingham risk for any cardiovascular event was 11.4%±9.2%. Brain infarcts were present in 25/228 (11%). All were ischemic (40% cortical, 56% lacunar, 4% both). Participants with infarcts were older than those without (48.9±9.4 versus 43.4±9.2, P=0.006). In a multivariable regression analysis, only age remained a significant predictor of brain infarcts (odds ratio 1.08, 95% CI 1.02-1.14, P=0.004). After controlling for age and education, the presence of infarct was a significant predictor of impaired decision making on the Iowa Gambling Task of decision making (ß -28.2, 95% CI -42.7 to -14.1, P<0.001). Conclusions Prevalence of infarcts on neuroimaging in this disadvantaged, community-dwelling cohort was much higher than expected for age and was associated with impaired decision making. Further research is needed to identify individuals at highest risk who may benefit from targeted preventative strategies.

How can we help African American substance users stop smoking? client and agency perspectives.

Research is needed to better understand barriers to smoking cessation and sustained abstinence among racial/ethnic minority polydrug users. We conducted community dialogue groups involving 49 clients in substance use treatment programs with predominantly ethnic minority clientele and individual dialogues/interviews with seven program providers (stakeholders). Most clients were African American, under 40 years old, women, current smokers, and high school graduates. Smoking cessation services in these programs were considered inadequate and community programs insufficiently culturally tailored and economically and geographically inaccessible. Participants discussed individual "willpower" and choice; agency tobacco-related programs and policies; the relationships between smoking, smoking cessation, and treatment goals; and steps needed to reshape agency services and policies to provide greater support for smoking cessation in this at-risk population.

Efficacy of a Chronic Care-Based Intervention on Secondary Stroke Prevention Among Vulnerable Stroke Survivors: A Randomized Controlled Trial.

BACKGROUND: Disparities of care among stroke survivors are well documented. Effective interventions to improve recurrent stroke preventative care in vulnerable populations are lacking. METHODS AND RESULTS: In a randomized controlled trial, we tested the efficacy of components of a chronic care model-based intervention versus usual care among 404 subjects having an ischemic stroke or transient ischemic attack within 90 days of enrollment and receiving care within the Los Angeles public healthcare system. Subjects had baseline systolic blood pressure (SBP) ≥120 mm Hg. The intervention included a nurse practitioner/physician assistant care manager, group clinics, self-management support, report cards, decision support, and ongoing care coordination. Outcomes were collected at 3, 8, and 12 months, analyzed as intention-to-treat, and used repeated-measures mixed-effects models. Change in SBP was the primary outcome. Low-density lipoprotein reduction, antithrombotic medication use, smoking cessation, and physical activity were secondary outcomes. Average age was 57 years; 18% were of black race; 69% were of Hispanic ethnicity. Mean baseline SBP was 150 mm Hg in both arms. SBP decreased to 17 mm Hg in the intervention arm and 14 mm Hg in the usual care arm; the between-arm difference was not significant (-3.6 mm Hg; 95% confidence interval, -9.2 to 2.2). Among secondary outcomes, the only significant difference was that persons in the intervention arm were more likely to lower their low-density lipoprotein <100 md/dL (2.0 odds ratio; 95% confidence interval, 1.1-3.5). CONCLUSIONS: This intervention did not improve SBP control beyond that attained in usual care among vulnerable stroke survivors. A community-centered component could strengthen the intervention impact. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT00861081.

Ki67 Proliferative Index in Carcinoid Tumors Involving Ovary.

Primary ovarian carcinoid tumors are rare neoplasms that constitute less than 0.1% of all ovarian carcinomas. However, carcinoid tumors metastatic to ovaries are more common. Cell proliferative rate is an important factor in the determination of neuroendocrine tumor prognosis. Limited data are available as regards Ki67 proliferation index in predicting the physiological features of carcinoid tumors involving the ovary. Pathology files of Mayo Clinic Rochester (1995-2014) were searched, and clinical information was collected from medical records. All cases were stained with an antibody against Ki67, and digital analysis was performed with digital imaging analysis. A total of 36 cases (median age 64 years, range 33-83 years), including 9 primary (median age 68 years, range 33-73 years) and 27 metastatic carcinoid cases (median age 64 years, range 36-83 years), were investigated in the current study. Seven out of nine (77.8%) primary ovarian carcinoids are associated with mature teratoma. Twenty two metastatic carcinoids (81.5%) were from the GI tract, four (14.8%) from the pancreas, and one (3.7%) from the posterior thorax location. There was significant difference of Ki67 index between primary (median 2.3%, range, 0.6-8.4%) and metastatic carcinoid tumors (median 9.7%, range, 1.3-46.7%) (p = 0.002). The survival time is much shorter among patients with metastatic carcinoid tumor (median survival 5.8 years) comparing to primary ovarian carcinoid tumor (median 14.2 years) (p = 0.0005). A strong association between Ki67 index and patient survival time was identified (Hazard ratio for 1-percentage point increase 1.11, p = 0.001). Comparing to primary ovarian carcinoid tumor, metastatic carcinoid usually exhibits a higher Ki67 index and a worse outcome.

Hematopoietic stem cell transplantation in 29 patients hemizygous for hypomorphic IKBKG/NEMO mutations.

X-linked recessive ectodermal dysplasia with immunodeficiency is a rare primary immunodeficiency caused by hypomorphic mutations of the IKBKG gene encoding the nuclear factor κB essential modulator (NEMO) protein. This condition displays enormous allelic, immunological, and clinical heterogeneity, and therapeutic decisions are difficult because NEMO operates in both hematopoietic and nonhematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is potentially life-saving, but the small number of case reports available suggests it has been reserved for only the most severe cases. Here, we report the health status before HSCT, transplantation outcome, and clinical follow-up for a series of 29 patients from unrelated kindreds from 11 countries. Between them, these patients carry 23 different hypomorphic IKBKG mutations. HSCT was performed from HLA-identical related donors (n = 7), HLA-matched unrelated donors (n = 12), HLA-mismatched unrelated donors (n = 8), and HLA-haploidentical related donors (n = 2). Engraftment was documented in 24 patients, and graft-versus-host disease in 13 patients. Up to 7 patients died 0.2 to 12 months after HSCT. The global survival rate after HSCT among NEMO-deficient children was 74% at a median follow-up after HSCT of 57 months (range, 4-108 months). Preexisting mycobacterial infection and colitis were associated with poor HSCT outcome. The underlying mutation does not appear to have any influence, as patients with the same mutation had different outcomes. Transplantation did not appear to cure colitis, possibly as a result of cell-intrinsic disorders of the epithelial barrier. Overall, HSCT can cure most clinical features of patients with a variety of IKBKG mutations.

Factors affecting severity of positive and negative symptoms of psychosis in a polysubstance using population with psychostimulant dependence.

Approximately half of psychostimulant users experience psychotic symptoms, which include both positive and negative symptoms. Prior reports have exclusively used positive symptoms to characterize psychostimulant associated psychosis. Symptoms vary dramatically in severity, though most investigations categorize psychosis as a dichotomous occurrence. To explore the association between different substances of abuse and the severity of psychotic symptoms, we investigated 171 individuals meeting DSM-IV-TR criteria for psychostimulant (cocaine or methamphetamine) dependence in an observational cross-sectional study. Participants were predominantly male (72.5%), recruited from a socially disadvantaged neighborhood in Vancouver, Canada, with a mean age of 45.5(±8.8) years. Of the total sample, 85% were dependent on cocaine, and 28.1% were dependent on methamphetamine. Participants had a median total PANSS score of 63, ranging from 37 to 111. Demographic information, current substance use and early substance exposure were used to predict positive and negative psychotic symptom severity in linear regression models. Increased severity of positive psychotic symptoms was significantly related to greater methamphetamine and marijuana use in the past 28 days, and methadone-abstinence. Negative symptom severity was related to increased opioid use in the past 28 days. There was no overlap between predictors of positive and negative symptom severity.