Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

High School Persisters: An Examination of College and Workforce Outcomes

This report examined the college and workforce outcomes of high school persisters, students who did not formally withdraw from high school, nor earn a regular high school diploma, four years after entering high school as a first-time ninth grader. We used data from the Maryland Longitudinal Data System (MLDS) to identify the population of students enrolled as first-time ninth graders in a Maryland public high school for a period of 90 days or more during the 2009-2010 academic year and attended a Maryland public high school in the 2012- 2013 academic year. The analyses conducted for this report identified a population of Maryland students who persisted into and through their fourth year of high school without earning a high school diploma that was larger than the population of students who dropped out of high school in their fourth year. Non-white and Hispanic students, as well as students in vulnerable subgroups (eligible for free and reduced price meals (FARMs), homeless, immigrant, English learners, and special education) tended to have less favorable outcomes in their fourth and fifth years of high school. Overall, persisters had more negative college and workforce outcomes when compared to students who earned a high school diploma. Policy implications and directions for future research are addressed

Remedial Coursework in Maryland: Examining Trends, High School Predictors, and College Outcomes

This report examined the trends in needing remedial coursework, the high school predictors of needing remedial coursework, and the college outcomes associated with needing remedial coursework in Maryland. Data from the Maryland Longitudinal Data System (MLDS) were used to link Maryland public high school graduate records to Maryland college enrollment and degree records. Sixty-seven percent of Maryland public high school graduates graduating in the 2013-2014 academic year who entered college in the 2014-2015 academic year were assessed for remedial coursework in any subject. Forty-one percent needed remedial coursework in any subject. Math was the most commonly assessed subject and was the subject in which students most commonly needed remedial coursework. Maryland two-year public institutions had the highest rates of students needing remedial coursework. Student demographic characteristics, high school program participation, high school attendance, and failing a high school assessment (HSA) were each associated with the likelihood of being assessed to need remedial coursework in college. Students assessed to need remedial coursework in college experienced more negative college outcomes when compared to students not assessed to need remedial coursework. These outcomes included poorer grades in the first non-remedial course taken, lower likelihood of earning a bachelor’s degree, and increased time to degree. Additionally, a lower percentage of students beginning in a two-year college who were assessed to need remedial coursework eventually transferred to and earned their final degree from a four-year college when compared to students not assessed to need remedial coursework. This report concludes with policy implications and future directions for research on remedial coursework in Maryland

Dual Enrollment in Maryland: A Report to the General Assembly and Governor Lawrence J. Hogan

A total of 5,453 Maryland 12th grade students were dually enrolled with overlapping enrollment dates in high school and a Maryland postsecondary institution in academic year 2013-2014. Overall, the total number of dually enrolled students in Maryland has increased 2% between the 2012-2013 and 2013-2014 academic years. This trend varies across school districts. The great majority of dually enrolled students were 12th grade students, but the percentages of dually enrolled students who were in 9th-11th grades have increased between the 2011-2012 and 2013-2014 academic years. The proportion of dually enrolled students that were female has remained stable across academic years (59%), with female students over-represented in dual enrollment participation in comparison to the proportion of female students in the 12th grade population (50%). Students eligible for free and reduced price meals (FARMs) are under-represented in dual enrollment participation. Racial minority students and Hispanic students are also under-represented in participation in dual enrollment, whereas White students are over-represented. Most dually enrolled students attended Maryland community colleges. A greater proportion of dually enrolled students (91%) enrolled in postsecondary education within one academic year when compared to the proportion of students in the population of Maryland 12th grade students (63%). However, this finding should be interpreted cautiously. In sum, a greater proportion of dually enrolled students are White, not Hispanic, Female, and not eligible for FARMs, and students with those characteristics generally enroll in postsecondary education at higher rates than other students. Such educational attainment gaps are generally seen as the result of those groups of students historically and currently not having equal access to effective educational programming or services. In addition to examining overlapping enrollment dates in high schools and postsecondary institutions to identify dually enrolled students, data from MHEC were used to identify students whom Maryland postsecondary institutions identified to be dually enrolled. This method is included in the report because it is the method used in prior MLDSC reports on dual enrollment, and it is the only method for which 2014-2015 data on dual enrollment are currently available. The number of dually enrolled high school students (from both public and private schools) identified by Maryland postsecondary institutions has substantially increased from 5,716 students in the 2013- 2014 academic year to 6,724 students in the 2014-2015 academic year, using this method of identifying students. This report is the first dual enrollment report that used merged cross agency data to identify dually enrolled students in Maryland. The benefit of cross agency data is that it provides a high level of confidence that the students identified are actually concurrently enrolled in both a high school and a postsecondary institution. As more years of data become available within the MLDS, additional trends can be reported. Future research on dual enrollment will examine the academic achievement of students who are dually enrolled compared to students who are not dually enrolled and will examine additional postsecondary educational outcomes, including retention, degree attainment, and time to degree