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Our purpose was to investigate the relationship between fetal and neonatal isomeric situs and maternal comorbidities. We identified all prenatally and postnatally diagnosed fetuses with left or right isomerism between March 2011 and October 2020 in Southern Nevada. We determined isomerism by the relationship of the abdominal inferior vena cava and descending aorta. For each case, we evaluated the presence of maternal comorbidities. We did not include routine obstetric ultrasound findings in determining the presence of maternal comorbidities. For each fetus or infant, we determined the presence of congenital heart disease. We did not analyze any other organ systems. We identified 48 cases. Of the 48, 31 (65%) occurred in mothers with comorbidities. Of the 48, 40 were live-born. Of the 40 live-born, 26 (65%) occurred with maternal comorbidities (p = 0.0001 for both the total and live-borns associated with maternal comorbidities). Of the 40 live-born, 1 had no prenatal care. Of the 39 with prenatal care, 38 (97%) were prenatally diagnosed. Of the 48 total cases: 23 had no congenital heart disease other than a patent foramen ovale, and 25 had critical congenital heart disease. Of the 23 without congenital heart disease, 19 (83%) were associated with maternal comorbidities, and of the 25 with critical congenital heart disease, 12 (48%) were associated with maternal comorbidities (p = 0.041). Prenatal detection of isomerism approached 100%. Most of those with isomerism occurred in association with maternal comorbidities. Most of those with critical congenital heart disease occurred in mothers without comorbidities.

Rationale: Current guidelines recommend patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia receive empirical antibiotics for suspected bacterial superinfection on the basis of weak evidence. Rates of ventilator-associated pneumonia (VAP) in clinical trials of patients with SARS-CoV-2 pneumonia are unexpectedly low. Objectives: We conducted an observational single-center study to determine the prevalence and etiology of bacterial superinfection at the time of initial intubation and the incidence and etiology of subsequent bacterial VAP in patients with severe SARS-CoV-2 pneumonia. Methods: Bronchoscopic BAL fluid samples from all patients with SARS-CoV-2 pneumonia requiring mechanical ventilation were analyzed using quantitative cultures and a multiplex PCR panel. Actual antibiotic use was compared with guideline-recommended therapy. Measurements and Main Results: We analyzed 386 BAL samples from 179 patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. Bacterial superinfection within 48 hours of intubation was detected in 21% of patients. Seventy-two patients (44.4%) developed at least one VAP episode (VAP incidence rate = 45.2/1,000 ventilator days); 15 (20.8%) initial VAPs were caused by difficult-to-treat pathogens. The clinical criteria did not distinguish between patients with or without bacterial superinfection. BAL-based management was associated with significantly reduced antibiotic use compared with guideline recommendations. Conclusions: In patients with SARS-CoV-2 pneumonia requiring mechanical ventilation, bacterial superinfection at the time of intubation occurs in

This study aimed to estimate prevalence of mild cognitive impairment (MCI) and dementia diagnoses in former National Football League (NFL) players ≥50 yr old and examine the relationships among these diagnoses and an array of predictors of long-term brain health.A cross section of former NFL players (n = 922; mean ± SD age, 64.8 ± 8.9 yr) completed a questionnaire. Prevalence of self-reported medical diagnoses of MCI and dementia was reported alongside U.S. population estimates across 5-yr age intervals (e.g., 60-64 yr). Prevalence ratios (PR) were calculated for multiple predictors of long-term brain health.Overall, MCI prevalence and dementia prevalence were n = 219(23.8%) and n = 82(8.9%), respectively. Each diagnosis was more prevalent in former NFL players across age-groups than U.S. norms, with greater disparities at relatively younger ages (e.g., 65-69 yr) compared with older ages. Greater prevalence of MCI and dementia was associated with self-reported concussion history (10+ vs 0; PRadjusted [95% CI] = 1.66 [1.02-2.71] and 2.61 [1.01-6.71], respectively); recent pain intensity (PRadjusted [95% CI] = 1.13 [1.07-1.20] and 1.15 [1.03-1.28]); and diagnoses of depression (PRadjusted [95% CI] = 2.70 [1.92-3.81] and 3.22 [1.69-6.14]), anxiety (PRadjusted [95% CI] = 1.96 [1.26-3.07] and 3.14 [1.47-6.74]), or both (PRadjusted [95% CI] = 3.11 [2.38-4.08] and 4.43 [2.71-7.25]). Higher MCI prevalence was related to sleep apnea (PRadjusted [95% CI] = 1.30 [1.06-1.60]); higher dementia prevalence was associated with age (5-yr interval, PRadjusted [95% CI] = 1.42 [1.26-1.60]) and race (non-White vs White, PRadjusted [95% CI] = 1.64 [1.07-2.53]).Self-reported MCI prevalence and dementia prevalence were higher in former NFL players than national estimates and were associated with numerous personal factors, including mood-related disorders and a high number of self-reported concussions. Predictors of higher MCI and dementia prevalence may be modifiable and warrant consideration by clinicians and researchers as potential targets to mitigate the onset of these conditions.

Objective We reviewed our center's experience with prenatal detection in Nevada's general population for young infants undergoing cardiovascular surgery. Methods We identified patients born in Nevada that underwent an initial cardiovascular surgery between 0 and 6 months old with birth dates between August 2012 and July 2021. Additionally, we calculated prenatal congenital cardiovascular malformation detection rates for each of the 9 years. Results We identified 660 patients. For the 660 patients, 649 (98%) mothers underwent prenatal care, which included at least one anatomical-survey obstetric ultrasound. Of the 649 with prenatal care, 395 (61%) had a prenatal diagnosis overall. However, prenatal diagnosis improved over the 9 years from 44% in 2012 to 79% in 2021 (correlation coefficient of 0.93, p = .00024). Conclusions Our results demonstrated a progressive rise in prenatal detection rates for young infants undergoing cardiovascular surgery in Nevada.

The STOP-Bang questionnaire is an established clinical screening tool to identify the risk of having mild, moderate or severe obstructive sleep apnoea using eight variables. It is unclear whether all eight variables contribute equally to the risk of clinically significant obstructive sleep apnoea. We analysed each variable for its contribution to detecting obstructive sleep apnoea; based on the results, we investigated whether the STOP-Bang questionnaire could be abbreviated to identify patients at high risk for severe obstructive sleep apnoea. We recruited patients with suspected obstructive sleep apnoea who were referred for overnight polysomnography. We used multivariable logistic regression to investigate the association of STOP-Bang parameters with severe obstructive sleep apnoea based on clinical and polysomnography data. Regression estimates were used to select variables to create the novel B-APNEIC score. We constructed receiver operating characteristic curves for the STOP-Bang questionnaire and B-APNEIC scores to identify patients with severe obstructive sleep apnoea and compared the areas under the curve using the DeLong method. Of the 275 patients enrolled, 32% (n = 88) had severe obstructive sleep apnoea. Logistic regression demonstrated that neck circumference (OR 2.20; 95%CI 1.10-4.40, p = 0.03) was the only variable independently associated with severe obstructive sleep apnoea. Observed apnoea during sleep, blood pressure and body mass index were the three next most closely trending predictors of severe obstructive sleep apnoea and were included along with neck circumference in the B-APNEIC score. Receiver operating curves demonstrated that the areas under the curve for STOP-Bang vs. B-APNEIC were comparable for identifying patients with severe obstructive sleep apnoea (OR 0.75; 95%CI 0.68-0.81 vs. OR 0.75; 95%CI 0.68-0.81: p = 0.99, respectively). Our results suggest that the B-APNEIC score is a simplified adaptation of the STOP-Bang questionnaire with equivalent effectiveness in identifying patients with severe obstructive sleep apnoea. Further studies are needed to validate and build on our findings.

OBJECTIVE We reviewed our center's experience with common arterial trunk. METHODS We included those with common arterial trunk in Nevada with estimated delivery dates or birth dates between June 2006 and May 2021. We excluded patients with functionally univentricular hearts. RESULTS We identified a total of 39: 32 prenatally and 7 postnatally. Of the 32 prenatally detected, 2 had elective termination, 2 had fetal demise, and 28 were live-born. Of the 7 postnatally diagnosed, 6 had prenatal care without a fetal echocardiogram, and 1 had no prenatal care. Overall, live-born prenatal detection was 28/34 (82%). Prenatal detection for 2006-2009 was 2/6 (33%) and for 2010-2021 was 26/28 (93%) p = .049. Of the 35 live-born infants, 1 died preoperatively, and 34 underwent neonatal surgery. Of the 34, 8 had palliation (birth weight 1.9±0.7 kg, range 0.8-2.6 kg), and 26 had a primary repair (birth weight 3.0±0.3 kg, range 2.6-4.0 kg) p = .0004. For all 34 neonatal surgical procedures, there were 2 (5.9%) deaths; however, there were no subsequent surgical or interventional catheterization mortalities. CONCLUSIONS In Nevada, current state-wide, general population prenatal detection of the common arterial trunk was more than 90%. By employing a combination of neonatal palliation and primary repair, surgical mortality was less than 6% in a cohort that included those with birth weights less than 2.5 kg, truncal valve surgery, and interrupted aortic arches.

Among elderly orthopedic trauma patients, the prevalence of delirium during hospitalization has been reported to be as high as 60%. Frail elderly patients have an increased risk of delirium after elective surgery; however, such an association remains underexplored among trauma patients. Our goal was to investigate whether preoperative frailty is associated with postoperative delirium (POD) in elderly orthopedic trauma patients. We conducted a single-center, retrospective, cross-sectional study. All patients were ≥ 65 years of age and were admitted to the hospital between 01/01/2017 and 08/31/2018 for surgical intervention of a significant extremity fracture. Frailty was assessed using the fatigue, resistance, ambulation, illness, and loss of weight questionnaire. Delirium was assessed using the Confusion Assessment Method. POD was defined as new-onset delirium that occurred within 24 h after surgery. To investigate whether frailty is associated with POD, we performed a multiple variable logistic regression, controlling for biologically relevant confounders. Five hundred fifty-six patients comprised the analytic cohort. Incidence of POD was 14% (n = 80). Multiple variable regression analysis demonstrated that each unit increment in FRAIL score was associated with a 33% higher likelihood of POD (OR 1.33; 95% CI 1.02–1.72, p = 0.03). Our results suggest that preoperative frailty increases the risk of POD in hospitalized, elderly, orthopedic trauma patients. Future studies are needed to determine whether perioperative interventions focused on improving frailty can reduce the risk of POD and improve outcomes in this rapidly growing cohort of patients.

Objective: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions. Study design and setting: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups. Results: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters. Conclusion: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis. (c) 2021 Elsevier Inc. All rights reserved.

We retrospectively analyzed our center's experience with the prenatal diagnosis of isolated perimembranous ventricular septal defects that underwent primary surgical repair in infancy.We identified patients born in Southern Nevada, between October 2012 and October 2020, with prenatal care that underwent surgical closure of an isolated large perimembranous ventricular septal defect between 1 and 12 months of age. The description at surgery defined ventricular septal defect morphology. We included only those with situs solitus, levocardia without dextroposition, and without any other cardiovascular abnormality. We analyzed prenatal detection rates for each of the eight years.We identified 81 patients. Of the 81, 35 (43%) had trisomy 21. We identified no other aneuploidies in those that underwent surgical repair; however, 1 had a 15q13.3 deletion syndrome, and 1 had a 22 q11.2 deletion syndrome. Of the 81, 27 (33%) overall were prenatally diagnosed. Increasing prenatal detection rates strongly correlated with time (Trisomy 21 is common in isolated perimembranous ventricular septal defects undergoing primary repair in infancy. Further, prenatal detection rates significantly improved over time, up to 65% detection in the current years.

Supplemental Digital Content is Available in the Text. From age 11 to 20 years, headache prevalence hardly changed in boys, but doubled in girls, often co-occurring with other unfavorable (mental) health conditions., The striking difference between men and women in headache prevalence is suggested to develop in adolescence. Although headaches are common and affect quality of life and daily functioning, the evidence needed to develop effective counselling and preventive approaches is still limited. Using data collected at age 11, 14, 17, and 20 years in the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort study (n = 3064 with ≥ 1 questionnaire), we assessed headache prevalence and incidence in girls and boys and explored associations with early life, environmental, lifestyle, health, and psychosocial factors. Associations were analysed longitudinally with generalized linear mixed models and discrete time hazard models. From age 11 to 20 years, the prevalence of headache increased from 9.4% to 19.8% in girls and hardly changed in boys (7.6%-6.1%). Headache commonly co-occurred with other unfavorable health and psychosocial conditions. Eighty-eight percent of the girls and 76% of boys with headache also reported at least one of the following at age 17: sleeping problems, asthma, hay fever, musculoskeletal complaints, fatigue, low mental health, or worrying. Results suggest higher headache prevalence in adolescents following lower educational tracks, in those who skip breakfast ≥2 days per week, and in boys exposed to tobacco smoke in infancy. In girls, sleeping problems and musculoskeletal complaints were associated with higher odds of incident headache and residential greenness with lower odds of incident headache. The high prevalence and strong female predominance of headache, already in adolescence and often with comorbidities, deserve recognition by professionals in (preventive) health care settings and schools.

Background Poor nutritional status is linked to suboptimal outcomes following elective surgery. Trauma patients do not typically have an opportunity for preoperative nutritional optimization and may be at risk for malnutrition with its related complications. Our goal was to investigate whether nutritional status is associated with development of hospital-acquired infections (HAIs) in elderly, orthopedic trauma patients. Methods We performed a retrospective analysis of data between 01/01/2017 to 08/30/2018 from the Massachusetts General Hospital Geriatric Inpatient Fracture Trauma Service (GIFTS). Admission nutritional status was assessed using the Mini Nutritional Assessment (MNA) and HAIs were validated through the American College of Surgeons National Surgical Quality Improvement Project database. To investigate whether nutritional status is associated with HAIs, we performed a multiple variable logistic regression analysis, controlling for age, sex, Charlson Comorbidity Index, glomerular filtration rate, and type of anesthesia. Results 461 patients comprised the analytic cohort. Multiple variable regression analysis demonstrated that each unit increment in MNA score was associated with a 13% reduction in risk of HAI (OR 0.87; 95%CI 0.79-0.97). Furthermore, adjusting for timing of perioperative antibiotics, perioperative transfusions, or development of pressure injury during hospitalization results did not materially change these results. Conclusion Our results demonstrate that malnutrition is highly prevalent in elderly orthopedic trauma patients and that nutritional status may influence the risk of developing HAIs in this cohort of patients. Further studies are needed to determine whether optimizing perioperative nutritional status in elderly orthopedic trauma patients can reduce infectious complications and improve overall health outcomes. This article is protected by copyright. All rights reserved.

OBJECTIVE We investigated a relationship between a composite index comprised of Fontan-circuit anatomical features and hepatic fibrosis scores from biopsy. METHODS We identified living extracardiac Fontan patients, ≥7 years old and ≥5 but

A persistent LSVC with an absent right superior vena cava (RSVC) is unusual, encountered in about 10% of patients with persistent LSVC. We present 14 patients with a prenatal diagnosis of single LSVC and situs solitus, including prenatal findings and information on medium-term follow-up. We identified patients with situs solitus and a persistent LSVC born between March 2004 and March 2020, which had been diagnosed prenatally between December 2003 and November 2019. From this cohort, we identified those with absent RSVC. In the population of women undergoing fetal echocardiography, the prevalence of persistent LSVC in situs solitus was 0.43% (84/19,712). For the 84 identified patients and for the entire population respectively, 14/84 (17%) and 14/19,712 (0.07%) had a single LSVC (absent RSVC). Of 14 patients with a single LSVC, 8 (57%) were male. For the 84 identified patients and for the entire population respectively, 70/84 (83%) and 70/19,712 (0.36%) had bilateral SVCs. For a single LSVC (absent RSVC) and situs solitus, the majority had no associated cardiac, extracardiac, or syndromic abnormalities.

Objective: We hypothesized that a relationship between post-Fontan hepatic fibrosis and anatomical variants might exist. Methods: Attempting to limit confounding variables, we analyzed data from living, stable, post-extracardiac Fontan patients who underwent cardiac catheterization and transvenous hepatic biopsy procedures between March 2012 and June 2020. Results: We identified 120 patients who met the inclusion criteria. Of the 120, 35 (29%) had pulmonary artery stents. For the 35 with pulmonary artery stents, the average total fibrosis score was 3.2 ± 1.9 and the fibrosis progression rate was 0.36 ± 0.33, and for those with no pulmonary artery stents, the total fibrosis score was 2.6 ± 1.8 and the fibrosis progression rate was 0.27 ± 0.33 ( P = .13 and P = .11, respectively). Of the 120, 65 had functional univentricles of right ventricular type. Of these 65, 27 had pulmonary artery stents. For the 27 with pulmonary artery stents, the average total fibrosis score was 3.4 ± 1.8 and the average fibrosis progression rate was 0.39 ± 0.30, and for the 38 without pulmonary artery stents, the average fibrosis score was 2.3 ± 1.5 and the average fibrosis progression rate was 0.23 ± 0.21 ( P = .01 for comparison of both values). Conclusions: This study’s findings suggest that a post-extracardiac Fontan with a functional univentricle of right ventricular type plus a pulmonary artery stent may have more advanced liver pathology than those without a pulmonary artery stent at similar Fontan duration years and ages at liver biopsy.

ObjectiveTo identify subgroups of former National Football League (NFL) players using latent profile analysis (LPA) and examine their associations with total years of participation (TYP) and self-reported lifetime sport-related concussion history (SR-CHx).MethodsFormer NFL players (N=686) aged 50–70 years, with an average 18.0 TYP (±4.5) completed a questionnaire. SR-CHx distributions included: low (0–3; n=221); intermediate (4–8; n=209) and high (9+; n=256). LPA measures included: Quality of Life in Neurological Disorders Emotional–Behavioral Dyscontrol, Patient Reported Outcomes Measurement Information System Cognitive Function, Emotional Support, Self-Efficacy, Meaning and Purpose, Physical Function, Pain Interference, Participation in Social Roles and Activities, Anxiety, Depression, Fatigue, and Sleep Disturbance. Demographic, medical/psychiatric history, current psychosocial stressors, TYP and SR-CHx were compared across latent profiles (LPs).ResultsA five profile solution emerged: (LP1) global higher functioning (GHF; 26.5%); (LP2) average functioning (10.2%); (LP3) mild somatic (pain and physical functioning) concerns (22.0%); (LP4) somatic and cognitive difficulties with mild anxiety (SCA; 27.5%); LP5) global impaired functioning (GIF; 13.8%). The GIF and SCA groups reported the largest number ofe- medical/psychiatric conditions and higher psychosocial stressor levels. SR-CHx was associated with profile group (χ2(8)=100.38, pConclusionsFive distinct profiles of self-reported functioning were identified among former NFL players. Several comorbid factors (ie, medical/psychiatric diagnoses and psychosocial stressors) and SR-CHx were associated with greater neurobehavioural and psychosocial dysfunction.

Background Prior spontaneous preterm birth is a strong risk factor for the recurrence of spontaneous preterm birth in a subsequent pregnancy and has been evaluated in prevention studies using progesterone (natural progesterone administered orally or vaginally, and 17-hydroxyprogesterone caproate [17-OHPC]) as a selection criterion. Based on the findings of a randomized, placebo-controlled study, 17-OHPC was approved for use in 2011 by the Food and Drug Administration in the USA for the prevention of recurrent preterm birth. The approval was granted with qualification that a subsequent confirmatory study would need to be carried out, the results of which have just been published (PROLONG trial). Method A systematic literature search for the period from 1970 to April 2020 using the search terms “preterm birth” and “17-OHPC” or “progesterone” was carried out. Only randomized, placebo-controlled studies of women with singleton pregnancies who received 17-OHPC to prevent recurrent preterm birth were included in the subsequent meta-analysis. The relative risk and associated 95% confidence intervals were calculated. The heterogeneity between studies was evaluated with I2 statistics. Results In addition to the original study used for the approval and the PROLONG trial, only one other study was found which met the inclusion criteria (total number of patients: 2221). With considerable heterogeneity between the studies, particularly with respect to the risk factors for preterm birth, the comparison between 17-OHPC and placebo showed no significant reduction in preterm birth rates before 37, 35 and 32 weeks of gestation and no significant differences with regard to the prevalence of miscarriage before 20 weeks of gestation or fetal deaths (antepartum or intrapartum) after 20 weeks of gestation and neonatal morbidity. Conclusion Based on the currently available data, 17-OHPC cannot be recommended for the prevention of recurrent preterm birth. Further randomized, placebo-controlled studies with clearly defined, comparable risk factors are required to identify the group of pregnant women which could benefit from the use of 17-OHPC to prevent preterm birth.

Objective: As part of an initiative led by the Brain Injury Special Interest Group Mild Traumatic Brain Injury (TBI) Task Force of the American Congress of Rehabilitation Medicine (ACRM) to update the 1993 ACRM definition of mild TBI, the present study aimed to characterize current expert opinion on diagnostic considerations. Design: Cross-sectional web-based survey. Setting: Not applicable. Participants: An international, interdisciplinary group of clinician-scientists (N=31) with expertise in mild TBI completed the survey by invitation between May and July 2019 (100% completion rate). Interventions: Not applicable. Main Outcome Measures: Ratings of agreement with statements related to the diagnosis of mild TBI and ratings of the importance of various clinical signs, symptoms, test findings, and contextual factors for increasing the likelihood that the individual sustained a mild TBI, on a scale ranging from 1 (“not at all important”) to 10 (“extremely important”). Results: Men (n=25; 81%) and Americans (n=21; 68%) were over-represented in the sample. The survey revealed areas of expert agreement (eg, acute symptoms are diagnostically useful) and disagreement (eg, whether mild TBI with abnormal structural neuroimaging should be considered the same diagnostic entity as “concussion”). Observable signs were generally rated as more diagnostically important than subjective symptoms (Wilcoxon signed ranks test, Z=3.77; P

The aim of this article is to develop a risk management procedure, which could be applied to the magnet design process, for both superconducting and normal magnets at the Jefferson Laboratory (JLab). This procedure allowed us to identify the key risks at each of the critical phases of design and propose procedures, tests, and checks to mitigate each risk. In this article, we present a qualitative and quantitative risk management procedure commonly referred to a “failure modes and effects analysis.” As part of this procedure, we calculated a risk priority number (RPN) for each activity of the process, identified the most critical activities and proposed mitigation activities, which in turn resulted in a revised RPN. Another benefit of this procedure was the identification of appropriate “control and hold” points within the design process, which allowed one to review and approve a particular outcome before proceeding to the next sequential activity.

Introduction Radiolabeling of stem cells with a positron emitting radioisotope represents a major advancement in regenerative biotherapy enabling non-invasive imaging. To assess the value of such an approach in a clinically relevant scenario, the tolerability and therapeutic aptitude of [89Zr]zirconium-p-isothiocyanatobenzyl-desferrioxamine ([89Zr]Zr-DBN) labeled human cardiopoietic stem cells (CPs) were evaluated in a model of ischemic heart failure. Methods and results [89Zr]Zr-DBN based radiolabeling of human CPs yielded [89Zr]Zr-DBN-CPs with radioactivity yield of 0.70 ± 0.20 MBq/106 cells and excellent label stability. Compared to unlabeled cell counterparts, [89Zr]Zr-DBN-CPs maintained morphology, viability, and proliferation capacity with characteristic expression of mesodermal and pro-cardiogenic transcription factors defining the cardiopoietic phenotype. Administered in chronically infarcted murine hearts, [89Zr]Zr-DBN-CPs salvaged cardiac pump failure, documented by improved left ventricular ejection fraction not inferior to unlabeled CPs and notably superior to infarcted hearts without cell treatment. Conclusion The present study establishes that [89Zr]Zr-DBN labeling does not compromise stem cell identity or efficacy in the setting of heart failure, offering a non-invasive molecular imaging platform to monitor regenerative biotherapeutics post-transplantation.

Objective The purpose of this study was to (1) examine the diagnostic utility of the King-Devick (KD) in professional ice hockey players and (2) determine whether the KD provides unique variance in predicting a diagnosis of concussion when given in combination with the SCAT-5. Study design Cohort Study. Setting Primary care. Patients/participants Professional ice hockey players. Independent variables Diagnosis versus no diagnosis of concussion. Main outcome measures King-Devick and SCAT-5 component scores. Methods In part 1, players suspected of having a concussion were evaluated at baseline and acutely with the KD and either the SCAT-3 or the SCAT-5. Players evaluated and not diagnosed with concussion served as active controls. In part 2, a separate group of players suspected of having a concussion was evaluated acutely with both the KD and SCAT-5. Results In part 1 of this study, 53 concussed players declined in performance on the KD from baseline to acute evaluation, whereas the performance of 76 active controls improved significantly. In part 2 of the study, 75 players were diagnosed with concussion and compared with 80 active controls who were evaluated and not diagnosed with concussion. Concussed players revealed a decline in KD performance from baseline to acute evaluation when compared with controls. However, the KD did not account for significant unique variance in predicting a diagnosis of concussion after accounting for SCAT-5 data. Conclusions The KD is useful in differentiating concussed and not concussed athletes acutely, but the KD does not seem to add additional diagnostic value over and above the SCAT-5.

Purpose: The aimwas to compare non-invasive blood pressuremeasurementswith invasive blood pressure measurements in critically ill patients. Methods: Non-invasive blood pressure was measured via automated brachial cuff oscillometry, and simultaneously the radial arterial catheter-derived measurement was recorded as part of a prospective observational study. Measurements of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) were compared using Bland-Altman and error grid analyses. Results: Paired measurements of blood pressurewere available for 736 patients. Observedmean difference (+/- SD, 95% limits of agreement) between oscillometrically and invasively measured blood pressure was 0.8 mmHg (+/- 15.7 mmHg, -30.2 to 31.7 mmHg) for SAP, -2.9 mmHg (+/- 11.0 mmHg, -24.5 to 18.6 mmHg) for DAP, and -1.0 mmHg (+/- 10.2 mmHg, -21.0 to 18.9 mmHg) for MAP. Error grid analysis showed that the proportions of measurements in risk zones A to E were 78.3%, 20.7%, 1.0%, 0%, and 0.1% for MAP. Conclusion: Non-invasive blood pressure measurements using brachial cuff oscillometry showed large limits of agreement compared to invasivemeasurements in critically ill patients. Error grid analysis showed that measurement differences between oscillometry and the arterial catheter would potentially have triggered at least lowrisk treatment decisions in one in five patients. (c) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

BACKGROUND/OBJECTIVES: Retinopathy of prematurity (ROP) is a severe neonatal complication potentially leading to visual impairment and blindness. Known risk factors include preterm birth, low birth weight and respiratory support. Limited and contradictory data exist on the risk of maternal smoking during pregnancy on the development of ROP. This study aims to investigate smoking as an independent risk factor for the development of severe ROP (≥stage 3). SUBJECTS/METHODS: This is a single centre retrospective case-control study of prospectively collected clinical data of infants born before 32 weeks of gestation between 2001 and 2012 at a tertiary care university hospital. The association between maternal smoking during pregnancy and the development of severe ROP was analyzed by multivariate logistic regression. RESULTS: In total, n = 751 infants born

Die Fruhgeburt tragt wesentlich zur perinatalen Morbiditat und Mortalitat bei und gilt als einer der Hauptrisikofaktoren fur „disability-adjusted life years“ (DALYs). Ihre Inzidenz liegt in Deutschland seit 2008 stabil bei etwas uber 8 %. Deutschland nimmt damit in Europa einen der hinteren Platze ein. Der Zustand nach Fruhgeburt ist der gewichtigste individuelle Risikofaktor fur eine erneute Fruhgeburt. Fur die Bitte ersetzen durch Gesamtfruhgeborenenrate einer Population sind allerdings die Nulliparitat und das mannliche fetale Geschlecht von deutlich groserer Bedeutung. Die Ursachen fur die erheblichen Unterschiede in der Fruhgeborenenrate zwischen einzelnen Landern gleicher Entwicklungsstufe sind zu grosen Teilen unklar. Durch den Einsatz verschiedener praventiver Masnahmen, z. B. Progesteron, Cerclage und Zervixpessar, lasst sich im individuellen Fall das Fruhgeburtsrisiko senken.

Despite safety concerns, β2-sympathomimetics are still widely used as tocolytic agents. β-Blockers in turn are used to treat vasculo-proliferative diseases of the newborn such as retinopathy of prematurity (ROP), which may lead to visual impairment and blindness. The scope of this study was to investigate whether antenatal exposure to the β2-sympathomimetic fenoterol contributes to the development of ROP. For this single-center retrospective case–control study of prospectively collected clinical data, all infants born before 32 weeks of gestation between 2001 and 2012 were included. The association of prenatal exposure to fenoterol and the development of ROP were analyzed by multivariate logistic regression. n = 1134 infants

Application of adhesive tape to the eyelids during general anesthesia decreases the risk of corneal abrasion but may increase the risk of eyelid injury. The aim of this study was to determine if there is a difference in eyelid erythema when covering the eyelid with either Tegaderm™ or an EyeGard®. We conducted a prospective, randomized, double-blind, split-face study of patients undergoing general anesthesia at an urban tertiary care academic medical centre. Each patient was randomized to having one eyelid covered with Tegaderm and the other with EyeGard. Photographs were taken prior to extubation and evaluated by three dermatologists. The primary outcome was the incidence of postoperative eyelid erythema. Secondary outcomes included the incidence of corneal abrasion and patient satisfaction. A total of 151 patients were included in our final analysis. Erythema was present on 117 (77%) eyelids covered with Tegaderm and 105 (70%) eyelids covered with EyeGard (% difference, 8; 95% confidence interval, 2 to 14; P = 0.03). No corneal abrasions were reported. The median [interquartile range] patient satisfaction score with eyelid condition was similar with Tegaderm vs EyeGard (5 [5–5] vs 5 [5–5], respectively; P = 0.84). We found a small increase in postoperative eyelid erythema when using Tegaderm compared with EyeGard. While EyeGard could decrease the risk of eyelid erythema, this should be balanced against other potential benefits of Tegaderm such as protection from fluids leaking onto the cornea. www.ClinicalTrials.gov (NCT03549429); registered 8 June, 2018.

Background and Purpose: Postmortem and experimental studies indicate a potential association between repeated concussions and stroke risk in older contact sport athletes. We examined the relationship between concussion and stroke history in former National Football League players aged ≥50 years. Methods: Former professional football players aged ≥50 years who played ≥1 year in the National Football League were enrolled in the cross-sectional study. Indirect standardization was used to calculate overall and decade-specific standardized prevalence ratios. Logistic regression using Firth’s bias reduction method examined the association between lifetime concussion history 0 (n=119; 12.2%), 1 to 2 (n=152; 15.5%), 3 to 5 (n=242; 24.7%), 6 to 9 (201; 20.5%), and 10+(n=265; 27.1%) and stroke. Adjusted odds ratios for stroke were calculated for concussion history groups, age, and coronary artery disease and/or myocardial infarction. Results: The 979 participants who met inclusion criteria had a mean age of 65.0±9.0 years (range, 50–99). The prevalence of stroke was 3.4% (n=33), significantly lower than expected based on rates of stroke in US men aged 50 and over (standardized prevalence ratio=0.56, Z= −4.56, P Conclusions: The prevalence of stroke among former National Football League players aged ≥50 years was lower than the general population, with significantly increased risk among those with 10 or more prior concussions. Findings add to the evidence suggesting that traumatic brain injuries are associated with increased risk of stroke. Clinically, management of cardio- and cerebrovascular health may be pertinent to those with a history of multiple prior concussions.

Background: Monitoring emerging trends in the increasingly dynamic European drug market is vital; however, information on change at the individual level is scarce. In the current study, we investigated changes in drug use over 12 months in European nightlife attendees. Method: In this longitudinal online survey, changes in substances used, use frequency in continued users, and relative initiation of use at follow-up were assessed for 20 different substances. To take part, participants had to be aged 18–34 years; be from Belgium, Italy, the Netherlands, Sweden, or the UK; and have attended at least 6 electronic music events in the past 12 months at baseline. Of 8,045 volunteers at baseline, 2,897 completed the survey at both time points (36% follow-up rate), in 2017 and 2018. Results: The number of people using ketamine increased by 21% (p < 0.001), and logarithmized frequency of use in those continuing use increased by 15% (p < 0.001; 95% CI: 0.07–0.23). 4-Fluoroamphetamine use decreased by 27% (p < 0.001), and logarithmized frequency of use in continuing users decreased by 15% (p < 0.001, 95% CI: −0.48 to −0.23). The drugs with the greatest proportion of relative initiation at follow-up were synthetic cannabinoids (73%, N = 30), mephedrone (44%, N = 18), alkyl nitrites (42%, N = 147), synthetic dissociatives (41%, N = 15), and prescription opioids (40%, N = 48). Conclusions: In this European nightlife sample, ketamine was found to have the biggest increase in the past 12 months, which occurred alongside an increase in frequency of use in continuing users. The patterns of uptake and discontinuation of alkyl nitrates, novel psychoactive substances, and prescription opioids provide new information that has not been captured by existing cross-sectional surveys. These findings demonstrate the importance of longitudinal assessments of drug use and highlight the dynamic nature of the European drug landscape.

Objectives:. Determine the variation in outcomes and respiratory mechanics between the subjects who are intubated earlier versus later in their coronavirus disease 2019 course. Design:. Retrospective cohort study. Setting:. Northwestern Memorial Hospital ICUs. Patients:. All patients intubated for coronavirus disease 2019 between March 2020 and June 2020. Interventions:. Patients were stratified by time to intubation: 30 subjects were intubated 4–24 hours after presentation and 24 subjects were intubated 5–10 days after presentation. Baseline characteristics, hospitalization, ventilator mechanics, and outcomes were extracted and analyzed. Ten clinically available CT scans were manually reviewed to identify evidence of pulmonary vascular thrombosis and intussusceptive angiogenesis. Measurements and Main Results:. Median time from symptom onset to intubation was significantly different between the early and late intubation cohorts, with the latter being intubated later in the course of their illness (7.9 vs 11.8 d; p = 0.04). The early intubation cohort had a lower mortality rate than the late intubation cohort (6% vs 30%, p < 0.001) without significantly different respiratory mechanics at the time of intubation. The late intubation cohort was noted to have higher dead space ratio (0.40 vs 0.52; p = 0.03). On review of CT scans, the late intubation cohort also had more dilated peripheral segments on imaging (two segments vs five segments). Conclusions:. The question as to whether delaying intubation is beneficial or harmful for patients with coronavirus disease 2019-induced hypoxemic respiratory failure has yet to be answered. As our approaches to coronavirus disease 2019 continue to evolve, the decision of timing of intubation remains paramount. Although noninvasive ventilation may allow for delaying intubation, it is possible that there are downstream effects of delayed intubation that should be considered, including the potential for pulmonary vascular thrombosis and intussusceptive angiogenesis with delayed intubation.

Background The objective of this study was to describe the prevalence, incidence, prognostic factors, and outcomes of venous thromboembolism in critically ill patients receiving contemporary thrombosis prophylaxis. Methods We conducted a pooled analysis of two prospective cohort studies. The outcomes of interest were in-hospital pulmonary embolism or lower extremity deep vein thrombosis (PE-LDVT), in-hospital nonleg deep vein thrombosis (NLDVT), and 90-day mortality. Multivariable logistic regression analysis was used to evaluate the association between predefined baseline prognostic factors and PE-LDVT or NLDVT. Cox regression analysis was used to evaluate the association between PE-LDVT or NLDVT and 90-day mortality. Results A total of 2208 patients were included. The prevalence of any venous thromboembolism during 3 months before ICU admission was 3.6% (95% CI 2.8–4.4%). Out of 2166 patients, 47 (2.2%; 95% CI 1.6–2.9%) developed PE-LDVT and 38 patients (1.8%; 95% CI 1.2–2.4%) developed NLDVT. Renal replacement therapy (OR 3.5 95% CI 1.4–8.6), respiratory failure (OR 2.0; 95% CI 1.1–3.8), and previous VTE (OR 3.6; 95% CI 1.7–7.7) were associated with PE-LDVT. Central venous catheters (OR 5.4; 95% CI 1.7–17.8) and infection (OR 2.2; 95% CI 1.1–4.3) were associated with NLDVT. Occurrence of PE-LDVT but not NLDVT was associated with increased 90-day mortality (HR 2.7; 95% CI 1.6–4.6, respectively, 0.92; 95% CI 0.41–2.1). Conclusion Thrombotic events are common in critically ill patients, both before and after ICU admittance. Development of PE-LDVT but not NLDVT was associated with increased mortality. Prognostic factors for developing PE-LDVT or NLDVT despite prophylaxis can be identified at ICU admission and may be used to select patients at higher risk in future randomized clinical trials. Trial registration NCT03773939.

Objective We reviewed our center's prenatal detection and surgical experience with high-risk, 2-ventricle patients, with complex congenital heart disease that underwent stage-1 hybrid palliation. Methods We retrospectively identified those born between March 2008 and March 2021 with 2-ventricle hearts, complex congenital cardiovascular malformations, and ductal-dependent systemic circulation that underwent stage-1 hybrid palliation consisting of surgical bilateral pulmonary artery banding and interventional catheterization placed ductus arteriosus stents. Results We identified 30 patients. Of the 30, 19 (63%) were male. For the 30, median gestational age was 35 weeks (29-39 weeks), and median birth weight was 2.2 kg (0.6-4.5 kg). Of the 30, 1 was transferred from an adjacent state, and 29 were born in Nevada. Of the 29 born in Nevada, overall statewide prenatal detection was 18 of 29 (62%); however, for 2008 to 2011 the prenatal detection rate was 3 of 10 (30%) and 15 of 19 (79%) for 2012 to 2021, P = .03. For the last 5 years, prenatal detection for Nevada-born patients was 8 of 8 (100%). Two full-term newborns, without a prenatal diagnosis, presented postnatally in extremis. For the 30 patients, there were 0 stage-1 hybrid palliation mortalities, 1 subsequent repair mortality, and 3 late nonsurgical deaths. Conclusions Stage-1 hybrid palliation may result in excellent surgical outcomes for high-risk, 2-ventricle patients. Additionally, high rates of population-wide prenatal detection are possible for high-risk congenital heart disease, allowing prenatal planning and possibly reducing postnatal extremis presentations.

We investigated the relationship between prenatal detection of significant congenital heart disease and elective termination of pregnancy over time in Nevada.We identified those prenatally or post-natally diagnosed with significant congenital cardiovascular malformations in Nevada with birth dates or estimated delivery dates between July 2012 and June 2021.We identified 1246. Of 1246, 69 underwent fetal demise, 42 had elective termination, and 1135 were live-born. Of the 1135 live-born, 1090 had prenatal care, of which 718 (66%) overall had a prenatal diagnosis of significant congenital heart disease. However, prenatal detection statistically significantly increased over time from 45 to 82%,In Nevada, despite a statistically significant increase in prenatal detection of significant congenital heart disease over time, termination of pregnancy rates did not increase. Nevertheless, those undergoing elective termination were more likely to have associated syndromes or comorbidities.

Critically ill patients constitute a highly heterogeneous population, with seemingly distinct patients having similar outcomes, and patients with the same admission diagnosis having opposite clinical trajectories. We aimed to develop a machine learning methodology that identifies and provides better characterization of patient clusters at high risk of mortality and kidney injury. We analysed prospectively collected data including co-morbidities, clinical examination, and laboratory parameters from a minimally-selected population of 743 patients admitted to the ICU of a Dutch hospital between 2015 and 2017. We compared four clustering methodologies and trained a classifier to predict and validate cluster membership. The contribution of different variables to the predicted cluster membership was assessed using SHapley Additive exPlanations values. We found that deep embedded clustering yielded better results compared to the traditional clustering algorithms. The best cluster configuration was achieved for 6 clusters. All clusters were clinically recognizable, and differed in in-ICU, 30-day, and 90-day mortality, as well as incidence of acute kidney injury. We identified two high mortality risk clusters with at least 60%, 40%, and 30% increased. ICU, 30-day and 90-day mortality, and a low risk cluster with 25–56% lower mortality risk. This machine learning methodology combining deep embedded clustering and variable importance analysis, which we made publicly available, is a possible solution to challenges previously encountered by clustering analyses in heterogeneous patient populations and may help improve the characterization of risk groups in critical care.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background The authors observed increased pharmaceutical costs after the introduction of sugammadex in our institution. After a request to decrease sugammadex use, the authors implemented a cognitive aid to help choose between reversal agents. The purpose of this study was to determine if sugammadex use changed after cognitive aid implementation. The authors’ hypothesis was that sugammadex use and associated costs would decrease. Methods A cognitive aid suggesting reversal agent doses based on train-of-four count was developed. It was included with each dispensed reversal agent set and in medication dispensing cabinet bins containing reversal agents. An interrupted time series analysis was performed using pharmaceutical invoices and anesthesia records. The primary outcome was the number of sugammadex administrations. Secondary outcomes included total pharmaceutical acquisition costs of neuromuscular blocking drugs and reversal agents, adverse respiratory events, emergence duration, and number of neuromuscular blocking drug administrations. Results Before cognitive aid implementation, the number of sugammadex administrations was increasing at a monthly rate of 20 per 1,000 general anesthetics (P < 0.001). Afterward, the monthly rate was 4 per 1,000 general anesthetics (P = 0.361). One month after cognitive aid implementation, the number of sugammadex administrations decreased by 281 per 1,000 general anesthetics (95% CI, 228 to 333, P < 0.001). In the final study month, there were 509 fewer sugammadex administrations than predicted per 1,000 general anesthetics (95% CI, 366 to 653; P < 0.0001), and total pharmaceutical acquisition costs per 1,000 general anesthetics were $11,947 less than predicted (95% CI, $4,043 to $19,851; P = 0.003). There was no significant change in adverse respiratory events, emergence duration, or administrations of rocuronium, vecuronium, or atracurium. In the final month, there were 75 more suxamethonium administrations than predicted per 1,000 general anesthetics (95% CI, 32 to 119; P = 0.0008). Conclusions Cognitive aid implementation to choose between reversal agents was associated with a decrease in sugammadex use and acquisition costs.

Introduction Low blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer's disease (AD). A fusion protein of EPO and a chimeric monoclonal antibody targeting the mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives EPO into the brain via receptor-mediated transcytosis across the BBB and increases its peripheral clearance to reduce hematopoietic side effects of EPO. Our previous work shows the protective effects of this BBB-penetrating EPO in AD mice but hematologic effects have not been studied. Herein, we investigate the hematologic safety and therapeutic effects of chronic cTfRMAb-EPO dosing, in comparison to recombinant human EPO (rhu-EPO), in AD mice. Methods Male APPswe PSEN1dE9 (APP/PS1) mice (9.5 months) were treated with saline (n = 11), and equimolar doses of cTfRMAb-EPO (3 mg/kg, n = 7), or rhu-EPO (0.6 mg/kg, n = 9) 2 days/week subcutaneously for 6 weeks, compared to saline-treated wild-type mice (n = 10). At 6 weeks, exploration and memory were assessed, and mice were sacrificed at 8 weeks. Spleens were weighed, and brains were evaluated for amyloid beta (Aβ) load and synaptophysin. Blood was collected at 4, 6 and 8 weeks for a complete blood count and white blood cells differential. Results cTfRMAb-EPO transiently increased reticulocyte counts after 4 weeks, followed by normalization of reticulocytes at 6 and 8 weeks. rhu-EPO transiently increased red blood cell count, hemoglobin and hematocrit, and significantly decreased mean corpuscular volume and reticulocytes at 4 weeks, which remained low at 6 weeks. At 8 weeks, a significant decline in red blood cell indices was observed with rhu-EPO treatment. Exploration and cognitive deficits were significantly worse in APP/PS1-rhu-EPO mice. Both cTfRMAb-EPO and rhu-EPO decreased 6E10-positive brain Aβ load; however, cTfRMAb-EPO and not rhu-EPO selectively reduced brain Aβ1-42 and elevated synaptophysin expression. Discussion Chronic treatment with cTfRMAb-EPO results in better hematologic safety, behavioral, and therapeutic indices compared with rhu-EPO, supporting the development of this BBB-penetrable EPO analog for AD., Highlights • Chimeric monoclonal antibody against the mouse TfR (cTfRMAb)-erythropoietin (EPO) is a brain-penetrating IgG-EPO fusion protein. • Chronic treatment with cTfRMAb-EPO does not alter hematology indices in APP/PS1 mice. • Equimolar dose of recombinant human EPO significantly alters hematologic indices in APP/PS1 mice. • Both cTfRMAb-EPO and recombinant human EPO reduce amyloid beta load in APP/PS1 mice. • cTfRMAb-EPO selectively reduces amyloid beta (1–42) and increases synaptophysin in APP/PS1 mice.

Supplemental Digital Content is available in the text., Objectives: Caregivers use clinical examination to timely recognize deterioration of a patient, yet data on the prognostic value of clinical examination are inconsistent. In the Simple Intensive Care Studies-I, we evaluated the association of clinical examination findings with 90-day mortality in critically ill patients. Design: Prospective single-center cohort study. Setting: ICU of a single tertiary care level hospital between March 27, 2015, and July 22, 2017. Patients: All consecutive adults acutely admitted to the ICU and expected to stay for at least 24 hours. Interventions: A protocolized clinical examination of 19 clinical signs conducted within 24 hours of admission. Measurements Main Results: Independent predictors of 90-day mortality were identified using multivariable logistic regression analyses. Model performance was compared with established prognostic risk scores using area under the receiver operating characteristic curves. Robustness of our findings was tested by internal bootstrap validation and adjustment of the threshold for statistical significance. A total of 1,075 patients were included, of whom 298 patients (28%) had died at 90-day follow-up. Multivariable analyses adjusted for age and norepinephrine infusion rate demonstrated that the combination of higher respiratory rate, higher systolic blood pressure, lower central temperature, altered consciousness, and decreased urine output was independently associated with 90-day mortality (area under the receiver operating characteristic curves = 0.74; 95% CI, 0.71–0.78). Clinical examination had a similar discriminative value as compared with the Simplified Acute Physiology Score-II (area under the receiver operating characteristic curves = 0.76; 95% CI, 0.73–0.79; p = 0.29) and Acute Physiology and Chronic Health Evaluation-IV (using area under the receiver operating characteristic curves = 0.77; 95% CI, 0.74–0.80; p = 0.16) and was significantly better than the Sequential Organ Failure Assessment (using area under the receiver operating characteristic curves = 0.67; 95% CI, 0.64–0.71; p < 0.001). Conclusions: Clinical examination has reasonable discriminative value for assessing 90-day mortality in acutely admitted ICU patients. In our study population, a single, protocolized clinical examination had similar prognostic abilities compared with the Simplified Acute Physiology Score-II and Acute Physiology and Chronic Health Evaluation-IV and outperformed the Sequential Organ Failure Assessment score.

We reviewed our recent experience with vascular rings and slings, including observations from diagnostic imaging and surgery. We analyzed data from all patients diagnosed with a vascular ring or sling between September 2015 and August 2018. Our definition of vascular rings or slings did not include a left aortic arch with an aberrant right subclavian artery, accompanied by a left ductus arteriosus or ligamentum. We identified 74 patients for analysis. Of the 74, 45 (61%) had a right aortic arch with aberrant left subclavian artery and left-sided ductus arteriosus or ligamentum, 14 (19%) had a right aortic arch with a left-sided ductus or ligamentum and a normal left subclavian artery, 11 (15%) had a double aortic arch, 2 (3%) had a pulmonary artery sling, and 2 (3%) had a left aortic arch with aberrant right subclavian artery and a right-sided ductus arteriosus or ligamentum. Of the 74 patients, 40 (54%) were born in Nevada between January 2017 and August 2018. Of these 40, 33 (83%) were diagnosed prenatally. For the period January 2017 to August 2018, there were approximately 54,000 live births in Nevada. For right aortic arch versus double aortic vascular rings, 31 had a right aortic arch vascular ring for a prevalence of 5.7 per 10,000 live births, and 6 had a double aortic arch vascular ring for a prevalence of 1.1 per 10,000 live births (p = 0.0001). Vascular rings are common congenital cardiovascular malformations, especially right aortic arch vascular rings. Further, a high percentage of vascular rings can be detected prenatally.

This paper provides an overview of the magnetic field measurement and subsequent electromagnetic re-modeling of the CLAS12 torus during the commissioning of the magnet in the fall of 2016. The CLAS12 detector in Hall B is part of the 12 GeV Accelerator Upgrade project at Jefferson Lab. The torus magnet allows precise determination of particle momenta within a cone ~ (5°-40°) in the forward direction. The ability to do this requires that we know the ∫B·dl of the torus to within an accuracy of 0.5% or better. To achieve this, an accurate model of the field along the particle path is required. The TOSCA code is used to generate a full three-dimensional (3-D) simulation of the magnetic envelope of the magnet as designed. Experimentally, the actual magnetic field within the magnet was surveyed to confirm the model design and to measure the deviation from the ideal case. The magnetic field deviations are attributed to manufacturing variability and assembly tolerances. A final model was created with allowances for these deviations guided by the survey data to create a more precise field integral model, which greatly improves the momentum resolution capability, allowing it to deliver the required specifications.

Numerous experimental studies indicate that natural progesterone, through various mechanisms, exerts an inhibitory effect on uterine contractility and sensitises the myometrium for tocolytics. It was therefore appropriate to investigate the possible benefits of oral/vaginal progesterone and the synthetic progesterone derivative 17-α-hydroxyprogesterone caproate, applied intramuscularly, in clinical studies on primary tocolysis, additively to established tocolytics (“adjunctive tocolysis”) and as maintenance treatment after successful tocolysis in cases of threatened preterm birth. Three studies with a small number of cases do not yield any sufficient evidence for recommending progesterone/17-α-hydroxyprogesterone caproate as primary tocolysis in women with preterm labour. There is also no evidence that progesterone or 17-α-hydroxyprogesterone caproate combined with commonly used tocolytics leads to a prolongation of pregnancy and a significant decrease in the rate of preterm birth. The data on the use of progesterone as maintenance treatment is controversial. While randomised, controlled studies with low quality showed promising results, studies with high quality did not reveal any significant differences with regard to the rate of preterm birth

Die S2k-Leitlinie der Deutschen (DGGG), Osterreichischen (OGGG) und Schweizerischen (SGGG) Gesellschaft fur Gynakologie und Geburtshilfe [1] hat evidenzbasiert die Diagnostik und Therapie des wiederholten Spontanaborts (WSA) anhand der aktuellen internationalen Literatur standardisiert. Dabei wurden die Empfehlungen und Statements in einem formalen Prozess erarbeitet und konsentiert. Insbesondere wurde auf die bekannten Risikofaktoren wie chromosomale, anatomische, endokrinologische, gerinnungsphysiologische, infektiologische und immunologische Storungen sowie die aktuellen Therapiemoglichkeiten eingegangen.

PURPOSE: Clinical examination is often the first step to diagnose shock and estimate cardiac index. In the Simple Intensive Care Studies-I, we assessed the association and diagnostic performance of clinical signs for estimation of cardiac index in critically ill patients.METHODS: In this prospective, single-centre cohort study, we included all acutely ill patients admitted to the ICU and expected to stay > 24 h. We conducted a protocolised clinical examination of 19 clinical signs followed by critical care ultrasonography for cardiac index measurement. Clinical signs were associated with cardiac index and a low cardiac index (RESULTS: We included 1075 patients, of whom 783 (73%) had a validated cardiac index measurement. In multivariable regression, respiratory rate, heart rate and rhythm, systolic and diastolic blood pressure, central-to-peripheral temperature difference, and capillary refill time were statistically independently associated with cardiac index, with an overall R2 of 0.30 (98.5% CI 0.25-0.35). A low cardiac index was observed in 280 (36%) patients. Sensitivities and positive and negative predictive values were below 90% for all signs. Specificities above 90% were observed only for 110/280 patients, who had atrial fibrillation, systolic blood pressures 4.5 s, or skin mottling over the knee.CONCLUSIONS: Seven out of 19 clinical examination findings were independently associated with cardiac index. For estimation of cardiac index, clinical examination was found to be insufficient in multivariable analyses and in diagnostic accuracy tests. Additional measurements such as critical care ultrasonography remain necessary.

Introduction: The adolescent years represent a key period for the development of musculoskeletal complaints (MSC) and the differences between boys and girls. We evaluated the prevalence and course of MSC and factors associated with MSC while growing up from age 11 to age 20. Methods: Questionnaire-based data at age 11 (n = 2,638), age 14 (n = 2,517), age 17 (n = 2,094) and at age 20 (n = 2,206) from the ongoing Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort were analyzed. MSC refers to pain of lower back, upper- and/or lower extremities. A multivariable logistic regression analysis was used to evaluate a number of factors in relation to persistent pain (pain reported at three out of four measurements). Results: Prevalence of MSC increased from 14.2% at age 11 to 22.1% at age 20 for boys, and from 17.4% at age 11 to 37.9% at age 20 for girls. Persistent pain was found among 5.1% of the boys and 16.5% of the girls. Being bullied, sleeping problems and tiredness during the day were significantly associated with persistent pain, in both boys and girls, while the latter two were more prevalent among girls. Self-reported (sports-) accidents, and among girls also early onset of puberty, were also significantly associated with persistent pain, but lifestyle factors, such as physical activity and smoking, were not. Conclusion: The prevalence of MSC increases during adolescence, with a widening gap between boys and girls. The factors associated with MSC are similar in boys and girls, though the prevalence of some of these differ by sex. Significance: Measuring a group of youngsters 4 times between age 11 and 20 shows an increase in the percentage reporting musculoskeletal complaints (MSC) with a widening gap between girls and boys, with more pain among girls. Boys and girls do hardly differ with respect to factors associated with MSC, being mainly psychosocial factors and (sports) accidents.

Ulcerative colitis (UC) is a disabling disease, characterized by chronic inflammation of the colon, with a rising prevalence worldwide in the pediatric age group. Although UC presents in children with varying severity, disease extent, and comorbidities, initial treatment is essentially uniform, consisting of 5-aminosalicylate drugs with corticosteroid induction for those with moderately to severely active disease. With the advent of anti-tumor necrosis factor (TNF) biologic therapy and several new biologics and small-molecule drugs for UC, precision medicine approaches to treatment are needed to more rapidly achieve sustained remission, restore quality of life, normalize development, and limit exposure to toxic corticosteroids in children with UC. Here, we review available data on clinical, biochemical, histopathologic, and molecular predictors of treatment response in UC. We also address known predictors and special treatment considerations in specific relevant scenarios such as very-early-onset UC, acute severe UC, ileal pouch anal anastomosis, and UC with concomitant primary sclerosing cholangitis. The review concludes with a prediction of how machine learning will integrate multimodal patient data to bring precision medicine to the bedside of children with UC in the future.

Introduction Despite extensive research, the goal of unravelling patient heterogeneity in critical care remains largely unattained. Combining clustering analysis of routinely collected high-frequency data with the identification of features driving cluster separation may constitute a step towards improving patient characterization. Methods In this study, we analysed prospectively collected data from 743 patients including co-morbidities, clinical examination, and laboratory parameters. We compared four clustering methodologies – deep embedded clustering (DEC), hierarchical clustering with and without dynamic time warping, and k-means – and trained a classifier to predict and validate cluster membership. The contribution of different variables to the predicted cluster membership was assessed using SHapley Additive exPlanations values.Results DEC yielded better results compared to the traditional clustering algorithms, with the best Jaccard and entropy scores being achieved for 6 clusters. These clusters were characterized as medium to high co-morbidity patients with respiratory pathology and sepsis (cluster 1), patients with primarily acute and chronic cardiac conditions and surgical admission (cluster 2), patients with diverse disease etiology and poor outcomes (cluster 3), low co-morbidity neurological, neurosurgical, and trauma patients (cluster 4), medium co-morbidity patients with cardio-respiratory problems, and neuro-trauma patients with longer length of stay (cluster 5), and patients with sepsis and respiratory infections (cluster 6). All clusters differed in in-ICU, 30-day, and 90-day mortality, as well as incidence of acute kidney injury, and two clusters were categorized as having higher mortality risk, and one cluster as lower mortality risk. Conclusions This machine learning methodology, which we made publicly available, is a possible solution to challenges previously encountered by clustering analyses, and may help unravel patient heterogeneity in critical care.

Background Discontinuity of care between childhood and adulthood is an identified problem for those with congenital heart disease. Objective This study investigated our center's discontinuity of care rate during this transition period. Methods The study cohort included those post-Fontan performed in childhood; those post-pulmonary valve, mitral valve, or aortic valve replacements initially performed between birth and age 17 years; those post-atrial switch operations; and those with biventricular hearts and discordance of atrioventricular and ventriculoarterial connections. We included patients born between 1978 and 2000 and cared for at our center initially from a prenatal diagnosis, birth, infancy, or childhood. We defined discontinuity of care as lack of continuing care until a minimum of 20 years of age, after excluding those that died before 20 years old or had documented continuing care at another center. We also tabulated patients that underwent at least one adult invasive procedure during continuous care. Results We identified 245 patients, of which 19 (7.8%) experienced discontinuity of care. Of the 226 in continuous care, 137 (60.6%) underwent 187 invasive procedures as adults: 36 cardiovascular surgeries, 82 surveillance cardiac catheterizations with or without transvenous liver biopsy, 32 interventional cardiac catheterizations, and 37 electrophysiology procedures with or without a pacemaker procedure. Conclusion We found a low, 7.8% discontinuity of care rate for adults with complex congenital heart disease at our center. Further, for adults with complex congenital heart disease, most required additional invasive procedures as adults.

Background Critical congenital heart disease is the target of postnatal, pulse-oximetry screening; nevertheless, prenatal detection is preferable. Prenatal diagnosis allows for advanced perinatal planning, parental counseling, potential fetal cardiac intervention if indicated, and avoidance of complicated, costly, and at times, risky neonatal transport. Objective The purpose of this study was to investigate a possible association between the occurrence of critical congenital heart disease and pregnancies complicated by maternal comorbidities. Methods We identified all those prenatally and postnatally diagnosed with critical congenital heart disease in Nevada between July 2014 and June 2020. For each identified case of critical congenital heart disease, we assessed each mother's medical history. We divided pregnant women into two groups: 1) those with maternal comorbidities and 2) those without comorbidities. Results We identified 367 cases of critical congenital heart disease. Of the 367, 229 (62%) occurred in those with maternal comorbidities. Of the 367, 321 (87%) were live-born. Of the 321 live-born, 201 (63%) occurred in those with maternal comorbidities, however, the prevalence of maternal comorbidities in the general pregnancy population is not known. The majority of patients born with critical heart disease were born to mothers with comorbidities versus those without comorbidities for both the total and live-born cohorts (p = 0.00001). Of the 321 live-born, 10 had no prenatal care. Of the 311 with prenatal care, 248 (80%) were prenatally diagnosed. During the study period, there were approximately 210,000 live births in Nevada, for a prevalence of 15.2 (321/210,000) critical congenital cardiac malformations per 10,000 live births. Conclusion In Nevada, most of those with critical congenital heart disease are products of pregnancies complicated by maternal comorbidities. Further, the state-wide, live-born, critical congenital heart disease prenatal-detection rate was 80%.

Standard-of-care infliximab dosing regimens were developed prior to the routine use of therapeutic drug monitoring and identification of target concentrations. Not surprisingly, subtherapeutic infliximab concentrations in pediatric Crohn’s disease (CD) are common. The primary aim was to conduct a real-world pharmacokinetic (PK) evaluation to discover blood biomarkers of rapid clearance, identify exposure targets, and a secondary aim to translate PK modeling to the clinic. In a multicenter observational study, 671 peak and trough infliximab concentrations from 78 patients with CD were analyzed with a drug-tolerant assay (Esoterix; LabCorp, Calabasas, CA). Individual area under the curve (AUC) estimates were generated as a measure of drug exposure over time. Population PK modeling (nonlinear mixed-effect modeling) identified serum albumin, antibody to infliximab, erythrocyte sedimentation rate (ESR), and neutrophil CD64 as biomarkers for drug clearance. Week 14 and week 52 biochemical remitters (fecal calprotectin < 250 μg/g) had higher infliximab exposure (AUC) throughout induction. The optimal infliximab AUC target during induction for week 14 biochemical remission was 79,348 μg*h/mL (area under the receiver operating characteristic curve (AUROC) 0.77, [0.63–0.90], 85.7% sensitive, and 64.3% specific) with those exceeding the AUC target more likely to achieve a surgery-free week 52 biochemical remission (OR 4.3, [1.2–14.6]). Pretreatment predictors for subtherapeutic week 14 AUC included neutrophil CD64 > 6 (OR 4.5, [1.4–17.8]), ESR > 30 mm/h (OR 3.8, [1.4–11]), age < 10 years old (OR 4.2, [1.2–20]), and weight < 30 kg (OR 6.6, [2.1–25]). We created a decision-support PK dashboard with an iterative process and embedded the modeling program within the electronic health record. Model-informed precision dosing guided by real-world PKs is now available at the bedside in real-time.

Objective We hypothesized that a relationship might exist between angiographically demonstrable, post-Fontan venovenous collaterals, and hepatic fibrosis. Methods We analyzed data from post-Fontan patients that underwent cardiac catheterization and transvenous-hepatic biopsy procedures between March 2012 and March 2020. From innominate vein angiography, we determined those that either had or lacked venovenous collaterals. Additionally, we examined data from post-Fontan patients that underwent hepatic ultrasound, shear-wave elastography between January 2017 and March 2020. Results We identified 164 patients that met inclusion criteria. Of the 164, 101 (62%) had venovenous collaterals. Of the 101 with collaterals, average total fibrosis score (TFS) was 3.2 and the average rate of fibrosis progression was 0.28 vs an average TFS of 2.1 and an average fibrosis progression rate of 0.22 for those without collaterals (P = .00001 and P = .01, respectively). Of the 101 with collaterals, oxygen saturation was 91% ± 4% vs 93% ± 3% (P = .048) without collaterals. Of the 164, 86 (52%) underwent ultrasound shear-wave elastography. Of the 86 patients undergoing elastography, 50 (58%) were performed in those with collaterals, and 36 (42%) in those without collaterals. For the 50 with collaterals, average elastography values were 13.3 vs 11.2 kPa for the 36 without collaterals (P = .006). We found no statistically significant differences for age at biopsy, Fontan duration, Fontan-type, type of functional univentricle, laboratory, clinical, or hemodynamic values between those with or without collaterals. Conclusions The presence of angiographically demonstrated venovenous collaterals was associated with statistically, significantly more advanced liver fibrosis than those without collaterals.

OBJECTIVE We reviewed our center's isolated vascular ring data. METHODS Inclusion criteria were patients born in Nevada between June 2015 and July 2020 with situs solitus, levocardia, atrioventricular and ventriculoarterial concordance, and no significant intracardiac malformations. RESULTS We identified 95 patients. Of the 95, 56 (59%) were female (p = .033). For the study period, there were approximately 180,000 live births, for a prevalence of 5.3 isolated vascular rings per 10,000 live births. Of the 95, 78 (82%) were prenatally diagnosed. Of the 95, 63 (66%) were products of high-risk pregnancies (p = .0001). Additionally, we found advanced maternal age was an isolated vascular ring risk factor (relative risk ratio, 2.7; 95% confidence interval, 1.8, 4.1; p