Plasmalemmal Vesicle Associated Protein-1 (PV-1) is a marker of blood-brain barrier disruption in rodent models

<p>Abstract</p> <p>Background</p> <p><it>Plasmalemmal vesicle associated protein-1 </it>(<it>PV-1</it>) is selectively expressed in human brain microvascular endothelial cells derived from clinical specimens of primary and secondary malignant brain tumors, cerebral ischemia, and other central nervous system (CNS) diseases associated with blood-brain barrier breakdown. In this study, we characterize the murine CNS expression pattern of <it>PV-1 </it>to determine whether localized <it>PV-1 </it>induction is conserved across species and disease state.</p> <p>Results</p> <p>We demonstrate that <it>PV-1 </it>is selectively upregulated in mouse blood vessels recruited by brain tumor xenografts at the RNA and protein levels, but is not detected in non-neoplastic brain. Additionally, <it>PV-1 </it>is induced in a mouse model of acute ischemia. Expression is confined to the cerebovasculature within the region of infarct and is temporally regulated.</p> <p>Conclusion</p> <p>Our results confirm that <it>PV-1 </it>is preferentially induced in the endothelium of mouse brain tumors and acute ischemic brain tissue and corresponds to blood-brain barrier disruption in a fashion analogous to human patients. Characterization of <it>PV-1 </it>expression in mouse brain is the first step towards development of rodent models for testing anti-edema and anti-angiogenesis therapeutic strategies based on this molecule.</p

The Risk Assessment and Prediction Tool (RAPT) for Discharge Planning in a Posterior Lumbar Fusion Population

BACKGROUND: As the use of bundled care payment models has become widespread in neurosurgery, there is a distinct need for improved preoperative predictive tools to identify patients who will not benefit from prolonged hospitalization, thus facilitating earlier discharge to rehabilitation or nursing facilities.OBJECTIVE: To validate the use of Risk Assessment and Prediction Tool (RAPT) in patients undergoing posterior lumbar fusion for predicting discharge disposition.METHODS: Patients undergoing elective posterior lumbar fusion from June 2016 to February 2017 were prospectively enrolled. RAPT scores and discharge outcomes were recorded for patients aged 50 yr or more (n = 432). Logistic regression analysis was used to assess the ability of RAPT score to predict discharge disposition. Multivariate regression was performed in a backwards stepwise logistic fashion to create a binomial model.RESULTS: Escalating RAPT score predicts disposition to home (P \u3c .0001). Every unit increase in RAPT score increases the chance of home disposition by 55.8% and 38.6% than rehab and skilled nursing facility, respectively. Further, RAPT score was significant in predicting length of stay (P = .0239), total surgical cost (P = .0007), and 30-d readmission (P \u3c .0001). Amongst RAPT score subcomponents, walk, gait, and postoperative care availability were all predictive of disposition location (P \u3c .0001) for both models. In a generalized multiple logistic regression model, the 3 top predictive factors for disposition were the RAPT score, length of stay, and age (P \u3c .0001, P \u3c .0001 and P = .0001, respectively).CONCLUSION: Preoperative RAPT score is a highly predictive tool in lumbar fusion patients for discharge disposition

The Utility of Cervical Spine Bracing As a Postoperative Adjunct to Multilevel Anterior Cervical Spine Surgery

Background: Use of cervical bracing/collar subsequent to anterior cervical spine discectomy and fusion (ACDF) is variable. Outcomes data regarding bracing after ACDF are limited. Here, we study the impact of bracing on short-term outcomes related to safety, quality of care, and direct costs in multilevel ACDF.Methods: Retrospective cohort analyses of all consecutive patients undergoing multilevel ACDF with or without bracing from 2013 to 2017 was undertaken (n = 616). Patient demographics and comorbidities were analyzed. Tests of independence and logistic regressions were used to assess differences in length of stay (LOS), discharge disposition (home, assisted rehabilitation facility [ARF], or skilled nursing facility [SNF]), quality-adjusted life year (QALY), direct cost, readmission within 30 days, and emergency room (ER) visits within 30 days.Results: Amongst the study population, 553 were braced and 63 were not braced. There was no difference in comorbidities (P \u3e .05) such as obesity, smoking, chronic obstructive pulmonary disease, hypertension, coronary artery disease, congestive heart failure, and problem list number. A significant difference in American Society of Anesthesiologists (ASA) score was found, with more ASA 2 patients in the braced cohort and more ASA 3 patients in the unbraced cohort (P = .007). LOS was extended for the unbraced group (median 156.9 +/- 211.4 versus 86.67 +/- 130.6 h, P = .003), and ER visits within 30 days were 0.21 times less likely in the braced group (P = .006). There was no difference in readmission (P = .181), QALY gain (P = .968), and direct costs (P = .689).Conclusion: Bracing following multilevel cervical fixation does not alter short-term postoperative course or reduce the risk for early adverse outcomes in a significant manner

Short-Term Impact of Bracing in Multi-Level Posterior Lumbar Spinal Fusion

Background: Clinical practice in postoperative bracing after posterior lumbar spine fusion (PLF) is inconsistent between providers. This paper attempts to assess the effect of bracing on short-term outcomes related to safety, quality of care, and direct costs. Methods: Retrospective cohort analysis of consecutive patients undergoing multilevel PLF with or without bracing (2013-2017) was undertaken (n = 980). Patient demographics and comorbidities were analyzed. Outcomes assessed included length of stay (LOS), discharge disposition, quality-adjusted life years (QALY), surgical-site infection (SSI), total cost, readmission within 30 days, and emergency department (ED) evaluation within 30 days. Results: Amongst the study population, 936 were braced and 44 were not braced. There was no difference between the braced and unbraced cohorts regarding LOS (P = .106), discharge disposition (P = .898), 30-day readmission (P = .434), and 30-day ED evaluation (P = 1.000). There was also no difference in total cost (P = .230) or QALY gain (P = .740). The results indicate a significantly lower likelihood of SSI in the braced population (1.50% versus 6.82%, odds ratio = 0.208, 95% confidence interval = 0.057-0.751, P = .037). There was no difference in relevant comorbidities (P = .259-1.000), although the braced cohort was older than the unbraced cohort (63 versus 56 y, P = .003). Conclusion: Bracing following multilevel posterior lumbar fixation does not alter short-term postoperative course or reduce the risk for early adverse events. Cost analysis show no difference in direct costs between the 2 treatment approaches. Short-term data suggest that removal of bracing from the postoperative regimen for PLF will not result in increased adverse outcomes

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.814.4 million) incident T2D cases, representing 70.3% (68.871.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.027.1%)), excess refined rice and wheat intake (24.6% (22.327.2%)) and excess processed meat intake (20.3% (18.323.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.487.7%)) and Latin America and the Caribbean (81.8% (80.183.4%)); and lowest proportional burdens were in South Asia (55.4% (52.160.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally. (c) 2023, The Author(s)

Children's and adolescents' rising animal-source food intakes in 1990-2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the worlds child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 1519 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes. (c) 2023, The Author(s)

Children’s and adolescents’ rising animal-source food intakes in 1990–2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents’ physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world’s child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15–19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.publishedVersio

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.8–14.4 million) incident T2D cases, representing 70.3% (68.8–71.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.0–27.1%)), excess refined rice and wheat intake (24.6% (22.3–27.2%)) and excess processed meat intake (20.3% (18.3–23.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.4–87.7%)) and Latin America and the Caribbean (81.8% (80.1–83.4%)); and lowest proportional burdens were in South Asia (55.4% (52.1–60.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally.publishedVersio

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030