Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry

Background and Aims Genetic predisposition to autoimmune hepatitis (AIH) in adults is associated with possession of human leukocyte antigen (HLA) class I (A*01, B*08) and class II (DRB1*03, ‐04, ‐07, or ‐13) alleles, depending on geographic region. Juvenile autoimmune liver disease (AILD) comprises AIH‐1, AIH‐2, and autoimmune sclerosing cholangitis (ASC), which are phenotypically different from their adult counterparts. We aimed to define the relationship between HLA profile and disease course, severity, and outcome in juvenile AILD. Approach and Results We studied 236 children of European ancestry (152 female [64%], median age 11.15 years, range 0.8‐17), including 100 with AIH‐1, 59 with AIH‐2, and 77 with ASC. The follow‐up period was from 1977 to June 2019 (median 14.5 years). Class I and II HLA genotyping was performed using PCR/sequence‐specific primers. HLA B*08, ‐DRB1*03, and the A1‐B8‐DR3 haplotype impart predisposition to all three forms of AILD. Homozygosity for DRB1*03 represented the strongest risk factor (8.8). HLA DRB1*04, which independently confers susceptibility to AIH in adults, was infrequent in AIH‐1 and ASC, suggesting protection; and DRB1*15 (DR15) was protective against all forms of AILD. Distinct HLA class II alleles predispose to the different subgroups of juvenile AILD: DRB1*03 to AIH‐1, DRB1*13 to ASC, and DRB1*07 to AIH‐2. Possession of homozygous DRB1*03 or of DRB1*13 is associated with fibrosis at disease onset, and possession of these two genes in addition to DRB1*07 is associated with a more severe disease in all three subgroups. Conclusions Unique HLA profiles are seen in each subgroup of juvenile AILD. HLA genotype might be useful in predicting responsiveness to immunosuppressive treatment and course

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. Trial registration number: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Compromises in career-related decisions: Hypothetical choices, individual differences,and actual outcomes

This study examined the process, correlates, and outcomes of compromise in career-related decisions, as a test of Gottfredson's (2002) theory of circumscription and compromise. Sex-type, prestige, and work activities are important dimensions along which individuals consider occupational alternatives. However, because these dimensions naturally covary across occupations, it is difficult to make unequivocal statements about the relative importance of these dimensions. 194 college seniors (127 females, 44 males, 26 non-responses) took part in an experimentally manipulated occupational choice task. They also provided additional information about their grades, self-efficacy perceptions, personality and vocational interests, as well as their parents' education levels and occupations. Results from this study indicated that (for this predominantly female sample) preferred occupations tended to be more prestigious, and more feminine in sex-type than less preferred occupations. In addition, when individuals were forced to choose among unacceptable occupations, females tended to choose more feminine (less masculine) occupations over other occupations. Males also tended to choose the more feminine occupation, although markedly less so than females. When forced to choose among preferred alternatives, both males and females tended to choose options more consistent with their interests over those options less consistent with their interests. Individual differences on ability, socio-economic status, and self-efficacy were also found to positively predict which occupations participants found acceptable. However, personality differences did not (in general) predict differences in participants' occupational choices. Lastly, in a follow-up, post-graduation interview (n = 44), individuals who experienced discrepancies between their intended and actual post-graduation positions reported less satisfaction with these positions than individuals who did not experience discrepancies. Limitations and implications of this work are discussed

Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry

BACKGROUND AND AIMS: Genetic predisposition to autoimmune hepatitis (AIH) in adults is associated with possession of HLA class I (A*01, B*08) and class II alleles (DRB1*03, −04, −07 or −13), depending on geographic regions. Juvenile autoimmune liver disease (AILD) comprises AIH-1, AIH-2 and autoimmune sclerosing cholangitis (ASC), which are phenotypically different from their adult counterparts. We aimed to define the relationship between HLA profile and disease course, severity and outcome in juvenile AILD. METHODS: We studied 236 children of European ancestry [152 females (64%), median age 11.15 years, range 0.8–17], including 100 AIH-1, 59 AIH-2 and 77 ASC. The follow up period was from 1977 to June 2019 (median 14.5 years). Class I and II HLA genotyping was performed using PCR/sequence specific primers. RESULTS: HLA B*08, -DRB1*03 and the A1-B8-DR3 haplotype impart predisposition to all three forms of AILD. Homozygosity for DRB1*03 represented the strongest risk factor (8.8). HLA DRB1*04, which independently confers susceptibility to AIH in adults, was infrequent in AIH-1 and ASC, suggesting protection, and DRB1*15 (DR15) was protective against all forms of AILD. Distinct HLA class II alleles predispose to the different subgroups of juvenile AILD: DRB1*03 to AIH-1, DRB1*13 to ASC and DRB1*07 to AIH-2. Possession of homozygous DRB1*03 or of DRB1*13 is associated with fibrosis at disease onset, and possession of these two genes in addition to DRB1*07 is associated with a more severe disease in all three subgroups. CONCLUSION: Unique HLA profiles are seen in each subgroup of juvenile AILD. HLA genotype might be useful in predicting responsiveness to immunosuppressive treatment and course

Herbarium records do not predict rediscovery of presumed nationally extinct species

10.1007/s10531-012-0319-xBiodiversity and Conservation21102589-2599BONS

Worldwide Survey of COVID-19–Associated Arrhythmias

Background: Coronavirus disease 2019 (COVID-19) has led to over 1 million deaths worldwide and has been associated with cardiac complications including cardiac arrhythmias. The incidence and pathophysiology of these manifestations remain elusive. In this worldwide survey of patients hospitalized with COVID-19 who developed cardiac arrhythmias, we describe clinical characteristics associated with various arrhythmias, as well as global differences in modulations of routine electrophysiology practice during the pandemic. Methods: We conducted a retrospective analysis of patients hospitalized with COVID-19 infection worldwide with and without incident cardiac arrhythmias. Patients with documented atrial fibrillation, atrial flutter, supraventricular tachycardia, nonsustained or sustained ventricular tachycardia, ventricular fibrillation, atrioventricular block, or marked sinus bradycardia (heart rate<40 bpm) were classified as having arrhythmia. Deidentified data was provided by each institution and analyzed. Results: Data were collected for 4526 patients across 4 continents and 12 countries, 827 of whom had an arrhythmia. Cardiac comorbidities were common in patients with arrhythmia: 69% had hypertension, 42% diabetes, 30% had heart failure, and 24% had coronary artery disease. Most had no prior history of arrhythmia. Of those who did develop an arrhythmia, the majority (81.8%) developed atrial arrhythmias, 20.7% developed ventricular arrhythmias, and 22.6% had bradyarrhythmia. Regional differences suggested a lower incidence of atrial fibrillation in Asia compared with other continents (34% versus 63%). Most patients in North America and Europe received hydroxychloroquine, although the frequency of hydroxychloroquine therapy was constant across arrhythmia types. Forty-three percent of patients who developed arrhythmia were mechanically ventilated and 51% survived to hospital discharge. Many institutions reported drastic decreases in electrophysiology procedures performed. Conclusions: Cardiac arrhythmias are common and associated with high morbidity and mortality among patients hospitalized with COVID-19 infection. There were significant regional variations in the types of arrhythmias and treatment approaches

Worldwide survey of COVID-19–associated arrhythmias

Background: Coronavirus disease 2019 (COVID-19) has led to over 1 million deaths worldwide and has been associated with cardiac complications including cardiac arrhythmias. The incidence and pathophysiology of these manifestations remain elusive. In this worldwide survey of patients hospitalized with COVID-19 who developed cardiac arrhythmias, we describe clinical characteristics associated with various arrhythmias, as well as global differences in modulations of routine electrophysiology practice during the pandemic. Methods: We conducted a retrospective analysis of patients hospitalized with COVID-19 infection worldwide with and without incident cardiac arrhythmias. Patients with documented atrial fibrillation, atrial flutter, supraventricular tachycardia, nonsustained or sustained ventricular tachycardia, ventricular fibrillation, atrioventricular block, or marked sinus bradycardia (heart rate<40 bpm) were classified as having arrhythmia. Deidentified data was provided by each institution and analyzed. Results: Data were collected for 4526 patients across 4 continents and 12 countries, 827 of whom had an arrhythmia. Cardiac comorbidities were common in patients with arrhythmia: 69% had hypertension, 42% diabetes, 30% had heart failure, and 24% had coronary artery disease. Most had no prior history of arrhythmia. Of those who did develop an arrhythmia, the majority (81.8%) developed atrial arrhythmias, 20.7% developed ventricular arrhythmias, and 22.6% had bradyarrhythmia. Regional differences suggested a lower incidence of atrial fibrillation in Asia compared with other continents (34% versus 63%). Most patients in North America and Europe received hydroxychloroquine, although the frequency of hydroxychloroquine therapy was constant across arrhythmia types. Forty-three percent of patients who developed arrhythmia were mechanically ventilated and 51% survived to hospital discharge. Many institutions reported drastic decreases in electrophysiology procedures performed. Conclusions: Cardiac arrhythmias are common and associated with high morbidity and mortality among patients hospitalized with COVID-19 infection. There were significant regional variations in the types of arrhythmias and treatment approaches