Johnstonpettersson0557

Polygenic risk scores (PRSs) discriminate trait risks better than single genetic markers because they aggregate the effects of risk alleles from multiple genetic loci. Constructing pleiotropic PRSs and understanding heterogeneity, and the replication of PRS-trait associations can strengthen its applications. By using variational Bayesian multivariate high-dimensional regression, we constructed pleiotropic PRSs jointly associated with body mass index, systolic and diastolic blood pressure, total and high-density lipoprotein cholesterol in a sample of 18,108 Caucasians from three independent cohorts. We found that dissecting heterogeneity associated with birth year, which is a proxy of exogenous exposures, improved the replication of significant PRS-trait associations from 37.5% (6 of 16) in the entire sample to 90% (18 of 20) in the more homogeneous sample of individuals born before the year 1925. Our findings suggest that secular changes in exogenous exposures may substantially modify pleiotropic risk profiles affecting translation of genetic discoveries into health care.Background To determine the prevalence and severity of acute kidney injury (AKI) at different time frames in relation to gestational age (GA) and birthweight (BW) in extremely low gestational age neonates (ELGAN). Our hypothesis is that ELGAN with lower GA and lower BW have higher AKI rates. Methods A total of 923 ELGAN enrolled in the Preterm Erythropoietin Neuroprotection Trial were evaluated from birth until death or hospital discharge. AKI was defined according to kidney disease improving global outcomes (KDIGO) definition from clinically-derived serum creatinine (SCr) measurements. Severe AKI was defined as stage 2 or higher. Results For the entire cohort, 351/923 (38.0%, CI = 34.8-41.3%) had at least one episode of stage 1 or higher AKI and 168/923 (18.2%, CI = 15.7-20.7%) had at least one episode of severe (stage 2 or higher) AKI. The prevalence of AKI stage 1 or higher for the entire cohort during the early (days 3-7), middle (days 8-14), and late follow-up period (after day 14) was 112/923 (12.1%, CI = 10.0-14.3%), 142/891 (15.9%, CI = 13.5-18.4%), and 249/875 (28.5%, CI = 25.4-31.5%), respectively. The rates of severe AKI during the hospital course were 27.8%, 21.9%, 13.6%, and 9.4% for the 24-, 25-, 26-, and 27-week GA groups, respectively. AKI rates were significantly higher with decreasing GA and decreasing BW for stated time trends (all p less then 0.01 using tests for trend). Conclusions AKI is relatively common in ELGAN during their initial hospital course and is associated with lower GA and BW.Background Acute kidney injury (AKI) often occurs in pediatric patients who received allogeneic hematopoietic cell transplantation (HCT). We evaluated the risk and effect of HCT-related AKI in pediatric patients. Methods We retrospectively studied the survival and renal outcome of 69 children 100 days and 1-year posttransplant in our institution in 2004-2016. Stage-3 AKI developed in 34 patients (49%) until 100 days posttransplant. Results The 100-day overall survival (OS) rates of patients with stage-3 AKI were lower than those without it (76.5% vs. 94.3%, P = 0.035). The 1-year OS rates did not differ markedly between 21 post-100-day survivors with stage-3 AKI and 29 without it (80.8% vs. 87.9%, P = 0.444). The causes of 19 deaths included the relapse of underlying disease or graft failure (n = 11), treatment-related events (4), and second HCT-related events (4). Underlying disease of malignancy (crude hazard ratio (HR) 5.7; 95% confidence interval (CI), 2.20 to 14.96), > 1000 ng/mL ferritinemia (crude HR 4.29; 95% CI, 2.11 to 8.71), stem cell source of peripheral (crude HR 2.96; 95% CI, 1.22 to 7.20) or cord blood (crude HR 2.29; 95% CI, 1.03 to 5.06), and myeloablative regimen (crude HR 2.56; 95% CI, 1.24 to 5.26), were identified as risk factors for stage-3 AKI until 100 days posttransplant. Hyperferritinemia alone was significant (adjusted HR 5.52; 95% CI, 2.21 to 13.76) on multivariable analyses. Conclusions Hyperferritinemia was associated with stage-3 AKI and early mortality posttransplant. Pretransplant iron control may protect the kidney of pediatric HCT survivors.In the context of hematopoietic cell transplantation, hematopoietic stem/progenitor cells (HSPC) from the umbilical cord blood (UCB) present several advantages compared to adult sources including higher proliferative capacity, abundant availability and ease of collection, non-risk and painless harvesting procedure, and lower risk of graft-versus-host disease. However, the therapeutic utility of UCB HSPC has been limited to pediatric patients due to the low cell frequency per unit of UCB. The development of efficient and cost-effective strategies to generate large numbers of functional UCB HSPC ex vivo would boost all current and future medical uses of these cells. Herein, we describe a scalable serum-free co-culture system for the expansion of UCB-derived CD34+-enriched cells using microcarrier-immobilized human bone marrow-derived mesenchymal stromal cells as feeder cells.Elder abuse is an emerging worldwide public health, human right, and social priority for governments and health policy makers. The aim of the current study was to provide an in-depth quantitative analysis of literature on elder abuse published in academic journals. A bibliometric method was implemented using Scopus database for the study period from 1950 to 2017. The search strategy utilized specific keywords to retrieve relevant documents. One thousand eight hundred seventy-two documents appeared in Scopus when using the search strategy. The annual number of publications showed a fluctuating pattern in the past four decades. Publications on elder abuse originated mainly from Northern America and Western Europe. International research collaboration on elder abuse was relatively low. The mean number of authors per document was 1.4. The Journal of Elder Abuse and Neglect published almost one third of the retrieved documents. The Rush University was the most active institution and Professor Dong, X.Q. was the most active author in this field. The most frequently encountered keywords were risk factors, prevalence, intervention, prevention, dementia, and nursing homes. Physical abuse was the most common type of elder abuse studied followed by psychological and financial abuse. Elder abuse is under-researched and of limited priority in most world regions. Governments need to take into consideration preventive policies of elder abuse based on research findings.Background All-cause perioperative mortality rate (POMR) is a commonly reported metric to assess surgical quality. Benchmarking POMR remains difficult due to differences in surgical volume and case mix combined with the burden of reporting and leveraging this complex and high-volume data. We seek to determine whether the pooled and individual procedure POMR of each bellwether (cesarean section, laparotomy, management of open fracture) correlate with state-level all-cause POMR in the interest of identifying benchmark procedures that can be used to make standardized regional comparisons of surgical quality. Methods The Brazilian National Healthcare Database (DATASUS) was queried to identify unadjusted all-cause POMR for all patient admissions among public hospitals in Brazil in 2018. Bellwether procedures were identified as any procedure involving laparotomy, cesarean section, or treatment of open long bone fracture and then classified as emergent or elective. The pooled POMR of all bellwether procedures as wel emergency cesarean section (0.05%) did not correlate with all-procedure POMR (p = 0.400). There was a correlation between surgical volume and emergency laparotomy POMR (r = - 0.53, p = .004), but not for emergency cesarean section or open, long bone fractures POMR. Conclusion Procedure-specific POMR for laparotomy and open long bone fracture correlates modestly with all-procedure POMR among Brazilian states which is primarily driven by emergency procedure POMR. Selective reporting of emergency laparotomy and open fracture POMR may be a useful surrogate to guide subnational surgical policy decisions.Introduction In the 5 months since it began, the COVID-19 pandemic has placed extraordinary demands on health systems around the world including surgery. Competing health objectives and resource redeployment threaten to retard the scale-up of surgical services in low- and middle-income countries where access to safe, affordable and timely care is low. The key aspiration of the Lancet Commission on global surgery was promotion of resilience in surgical systems. The current pandemic provides an opportunity to stress-test those systems and identify fault-lines that may not be easily apparent outside of times of crisis. Methods We endeavoured to explore vulnerable points in surgical systems learning from the experience of past outbreaks, using examples from the current pandemic, and make recommendations for future health emergencies. The 6-component framework for surgical systems planning was used to categorise the effects of COVID-19 on surgical systems, with a particular focus on low- and middle-income countries. Key vulnerabilities were identified and recommendations were made for the current pandemic and for the future. Results Multiple stress points were identified throughout all of the 6 components of surgical systems. The impact is expected to be highest in the workforce, service delivery and infrastructure domains. Innovative new technologies should be employed to allow consistent, high-quality surgical care to continue even in times of crisis. Conclusions If robust progress towards global surgery goals for 2030 is to continue, the stress points identified should be reinforced. An ongoing process of reappraisal and fortification will keep surgical systems in low- and middle-income countries responsive to "old threats and new challenges". Multiple opportunities exist to help realise the dream of surgical systems resilient to external shocks.Background Hepatic resection carries a high risk of parenchymal bleeding both intra- and post-operatively. Topical haemostatic agents are frequently used to control bleeding during hepatectomy, with multiple products currently available. However, it remains unknown which of these is most effective for achieving haemostasis and improving peri-operative outcomes. Methods A systematic review and random-effects Bayesian network meta-analysis of randomised trials investigating topical haemostatic agents in hepatic resection was performed. Interventions were analysed by grouping into similar products; fibrin patch, fibrin glue, collagen products, and control. Primary outcomes were the rate of haemostasis at 4 and 10 min. Results Twenty randomized controlled trials were included in the network meta-analysis, including a total of 3267 patients and 7 different interventions. Fibrin glue and fibrin patch were the most effective interventions for achieving haemostasis at both 4 and 10 min. There were no significant differences between haemostatic agents with respect to blood loss, transfusion requirements, bile leak, post-operative complications, reoperation, or mortality. Conclusions Amongst the haemostatic agents currently available, fibrin patch and fibrin glue are the most effective methods for reducing time to haemostasis during liver resection, but have no effect on other peri-operative outcomes. Topical haemostatic agents should not be used routinely, but may be a useful adjunct to achieve haemostasis when needed.