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Children with glomerular disease have unique risk factors for compromised bone health. Studies addressing skeletal complications in this population are lacking.This retrospective cohort study utilized data from PEDSnet, a national network of pediatric health systems with standardized electronic health record data for more than 6.5 million patients from 2009 to 2021. Incidence rates (per 10,000 person-years) of fracture, slipped capital femoral epiphysis (SCFE), and avascular necrosis/osteonecrosis (AVN) in 4598 children and young adults with glomerular disease were compared with those among 553,624 general pediatric patients using Poisson regression analysis. The glomerular disease cohort was identified using a published computable phenotype. Inclusion criteria for the general pediatric cohort were two or more primary care visits 1 year or more apart between 1 and 21 years of age, one visit or more every 18 months if followed3 years, and no chronic progressive conditions defined by the Pediatric Medical Complexity Algorithm. Fracture, SCFE, and AVN were identified using SNOMED-CT diagnosis codes; fracture required an associated x-ray or splinting/casting procedure within 48 hours.We found a higher risk of fracture for the glomerular disease cohort compared with the general pediatric cohort in girls only (incidence rate ratio [IRR], 1.6; 95% CI, 1.3 to 1.9). Hip/femur and vertebral fracture risk were increased in the glomerular disease cohort: adjusted IRR was 2.2 (95% CI, 1.3 to 3.7) and 5 (95% CI, 3.2 to 7.6), respectively. For SCFE, the adjusted IRR was 3.4 (95% CI, 1.9 to 5.9). For AVN, the adjusted IRR was 56.2 (95% CI, 40.7 to 77.5).Children and young adults with glomerular disease have significantly higher burden of skeletal complications than the general pediatric population.

Rodent models of early life adversity disrupt typical interactions between dams and offspring, impacting pup development over the lifespan. Predictability of caregiver interactions is a critical feature of the environment, and unpredictability is associated with behavioral and cognitive deficits in offspring. In the maternal separation (MS) paradigm, dams are not able to engage with pups while they are separated, and maternal care is impacted even after pups and dams are reunited. Using a 3.5-h daily MS protocol in rats, the present study sought to compare diurnal patterns of maternal behavior, specifically predictability and fragmentation of care, between MS- and control-reared dams. Three observation periods were assessed (1430, 2330, and 0830) between postnatal days 8-9. Frequencies and durations of maternal behaviors were measured, including pup-directed licking/grooming, arched-back and passive nursing, and carrying pups, as well as non-pup-directed self-grooming, rearing, burrowing, nest-building, and eating. The frequency of nest entries was interpreted as a measure of fragmentation, and entropy rate was calculated from transitional probability matrices to measure predictability of maternal behavioral sequences. After dam-pup reunion, MS dams engaged in more bouts of nursing and licking/grooming and more nest entries, and behavioral sequences were less predictable than control dams. MS-induced enhancement of care is a replication of previous research, but unpredictability and fragmented care during MS is a novel finding, as these measures have not been previously reported for MS.

Rationale: Dietary protein may attenuate the muscle atrophy experienced by patients in the ICU, yet protein handling is poorly understood. Objectives: To quantify protein digestion and amino acid absorption and fasting and postprandial myofibrillar protein synthesis during critical illness. Methods: Fifteen mechanically ventilated adults (12 male; aged 50 ± 17 yr; body mass index, 27 ± 5 kg⋅m-2) and 10 healthy control subjects (6 male; 54 ± 23 yr; body mass index, 27 ± 4 kg⋅m-2) received a primed intravenous L-[ring-2H5]-phenylalanine, L-[3,5-2H2]-tyrosine, and L-[1-13C]-leucine infusion over 9.5 hours and a duodenal bolus of intrinsically labeled (L-[1-13C]-phenylalanine and L-[1-13C]-leucine) intact milk protein (20 g protein) over 60 minutes. Arterial blood and muscle samples were taken at baseline (fasting) and for 6 hours following duodenal protein administration. Data are mean ± SD, analyzed with two-way repeated measures ANOVA and independent samples t test. Measurements and Main Results: Fasting myofibrillar protein synthesis rates did not differ between ICU patients and healthy control subjects (0.023 ± 0.013% h-1 vs. 0.034 ± 0.016% h-1; P = 0.077). After protein administration, plasma amino acid availability did not differ between groups (ICU patients, 54.2 ± 9.1%, vs. healthy control subjects, 61.8 ± 13.1%; P = 0.12), and myofibrillar protein synthesis rates increased in both groups (0.028 ± 0.010% h-1 vs. 0.043 ± 0.018% h-1; main time effect P = 0.046; P-interaction = 0.584) with lower rates in ICU patients than in healthy control subjects (main group effect P = 0.001). Incorporation of protein-derived phenylalanine into myofibrillar protein was ∼60% lower in ICU patients (0.007 ± 0.007 mol percent excess vs. 0.017 ± 0.009 mol percent excess; P = 0.007). Conclusions: The capacity for critically ill patients to use ingested protein for muscle protein synthesis is markedly blunted despite relatively normal protein digestion and amino acid absorption.

Reduced dorsolateral prefrontal cortex (dlPFC) activity and inhibitory control may contribute to obesity. The study objective was to assess effects of repeated transcranial direct current stimulation (tDCS) on food Go/No-Go (GNG), food Stroop performance, and snack food intake.Twenty-nine individuals with obesity (12 male; mean [SD], age 42 [11] years; BMI 39 [8]) participated in a combined inpatient/outpatient randomized parallel-design trial and received 15 sessions of anodal or sham tDCS to the left dlPFC. Food-related inhibitory control (GNG), attentional bias (Stroop), and snack food intake were assessed at baseline, completion of inpatient sessions (day 7), and follow-up (day 31).GNG performance improved in the anodal group by day 31, compared with sham (p = 0.01), but Stroop scores did not differ by intervention. Greater snack food intake was associated with lower GNG scores (p = 0.01), driven by the sham group (p 0.001) and higher food and palatable bias scores on the Stroop (all p = 0.02) across both groups. Changes on tasks were not associated with changes in intake.Anodal tDCS to the left dlPFC improved performance on a food-related inhibitory control task, providing evidence of potential for therapeutic benefit of neuromodulation in areas controlling executive function. Results showed that tDCS to the dlPFC reduced snack food intake and hunger; however, underlying neurocognitive mechanisms remain uncertain.

Physiological systems responsible for water homeostasis and energy metabolism are interconnected. This study hypothesized altered responses to dehydration including thirst, ad libitum water intake, and copeptin in men with obesity.Forty-two men (22 lean and 20 with obesity) were stimulated by a 2-hour hypertonic saline infusion and a 24-hour water deprivation. In each dehydrating condition, thirst, ad libitum water intake after dehydration, and urinary and hormonal responses including copeptin were assessed.After each dehydration condition, ad libitum water intake was similar between both groups (p 0.05); however, those with obesity reported feeling less thirsty (p 0.05) and had decreased copeptin response and higher urinary sodium concentrations when stressed (p 0.05). Angiotensin II, aldosterone, atrial and brain natriuretic peptides, and apelin concentrations did not differ by adiposity group and did not explain the different thirst or copeptin responses in men with obesity. However, leptin was associated with copeptin response in lean individuals during the hypertonic saline infusion (p 0.05), but the relationship was diminished in those with obesity.Diminished thirst and copeptin responses are part of the obesity phenotype and may be influenced by leptin. Adiposity may impact pathways regulating thirst and vasopressin release, warranting further investigation.

Deficiency and dysfunction of corneal cells leads to the blindness observed in corneal diseases such as limbal stem cell deficiency (LSCD) and bullous keratopathy. Regenerative cell therapies and engineered corneal tissue are promising treatments for these diseases [1]. However, these treatments are not yet clinically feasible due to inadequate cell sources. The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka has provided a multitude of opportunities in research because iPSCs can be generated from somatic cells, thus providing an autologous and unlimited source for corneal cells. Compared to other stem cell sources such as mesenchymal and embryonic, iPSCs have advantages in differentiation potential and ethical concerns, respectively. Efforts have been made to use iPSCs to model corneal disorders and diseases, drug testing [2], and regenerative medicine [1]. Autologous treatments based on iPSCs can be exorbitantly expensive and time-consuming, but development of stem cell banks with human leukocyte antigen (HLA)- homozygous cell lines can provide cost- and time-efficient allogeneic alternatives. In this review, we discuss the early development of the cornea because protocols differentiating iPSCs toward corneal lineages rely heavily upon recapitulating this development. Differentiation of iPSCs toward corneal cell phenotypes have been analyzed with an emphasis on feeder-free, xeno-free, and well-defined protocols, which have clinical relevance. The application, challenges, and potential of iPSCs in corneal research are also discussed with a focus on hurdles that prevent clinical translation.

Video capsule endoscopy (VCE) is an effective, noninvasive modality for small bowel (SB) investigation. Its usage in the older adults is rising. However, data in octa-nonagenarians regarding diagnostic yield and motility are lacking. Our aim was to evaluate and compare safety and efficacy of VCE between age subgroups of older adult patients.This was a retrospective study of prospectively documented data. All consecutive VCEs of patients ≥65 years (01/2010-12/2017) were included. Patients unable to swallow the capsule or videos with significant recording technical malfunction were excluded. The cohort was divided into the younger group aged 65-79 years old and octa-nonagenarians aged ≥80 years old. Indications for referral, diagnostic yield and transit times were compared between groups.A total of 535 VCEs were performed in 499 older adult patients (51.2% males); 82.8% were 65-79 years old and 17.2% were ≥80 years old. The ≥80-year-old group had higher rates of clinically significant findings (52.7% vs. 40.0%, p = 0.025), active bleeding (12.5% vs. 6.5%, p = 0.053) and angioectasia (36.0% vs. 23.4%, p = 0.014). Crohn's disease was newly diagnosed in approximately 8% of the entire cohort and 12% of the ≥80 years old. Anemia was the most common indication in both groups, followed by overt bleeding in the ≥80-year-old group (25% vs. 9.9% in 65-79-year-old group, p 0.001) and Crohn's disease in the 65-79 years old (17.2% vs. 5.4% in ≥80 years old, p = 0.004). Groups were comparable in transit time and cecal documentation rates.In octa-nonagenarians, VCE is as safe as in younger older-adults with a higher diagnostic yield of significant and treatable conditions.

With the implementation of the new heart transplant (HT) allocation system, patients requiring biventricular support systems have the highest priority, a shorter waitlist time, and a higher frequency of HT. However, the short-term and long-term outcomes of such patients are often disputed. Hence, we examined the outcomes of these patients who underwent HT before change in allocation scheme. Additionally, we compared post-HT outcomes of extracorporeal membrane oxygenation (ECMO) with other nondischargeable biventricular (BiVAD) supported patients. We identified adult ECMO or BiVAD supported HT recipients between 2000 and 2018 in the Scientific Registry of Transplant Recipients database. We compared survival with the Kaplan-Meier method. Using overlap propensity score weighting, we constructed Cox proportional hazards regression models to determine the risk-adjusted influence of BiVAD versus ECMO on survival. Of the 730 patients HT recipients; 528 (72.3%) and 202 (27.7%) were bridged with BiVAD and ECMO, respectively. For BiVAD versus ECMO patients, the 30-day, 1-year, 3-year, and 5-year mortality rates were 8.0% versus 14.4%, 16.3% versus 21.3%, 22.4% versus 25.3%, and 26.3% versus 25.7%, respectively. Risk-adjusted post-HT survival of BiVAD and ECMO patients at 30-day (HR 1.24 [95% CI, 0.68-2.27]; P = 0.4863), 1-year (HR 1.29 [95% CI, 0.80-2.09]; P = 0.3009), 3-year (HR 1.27 [95% CI, 0.83-1.94]; P = 0.2801), and 5-year (HR 1.35, 95% CI, 0.90-2.05; P = 0.1501) were similar. Around three-fourth of the ECMO or BiVAD supported patients were alive at 5-years post-HT. The short-term and long-term post-HT survivals of groups were comparable.

Workload plays important roles in sports-related injury and athletic performance by influencing exposure to external injury risk factors and potential events, promoting changes in fitness level, which involves positive adaptations to training that may lead to improved performance, and/or stimulating fatigue which leads to negative effects in the body that may increase the risk of injury and negatively affect performance. In addition to the physical stress and significant time required for practice and training, student athletes also face subjective stressors. The total workload affects injury risk, but acute changes or spikes in external and/or internal loads seem to affect injury risk the most. These also may lead to poor recovery practices that may affect physical and academic performance. It is important for the medical team, coaches, parents, and the student athlete to understand the vulnerability of this population to increased amounts of workload and its positive and negative effects.

OBJECTIVE: Food insecurity is known to be associated with obesity but its association with physiological measures is unclear. Therefore, we hypothesized that compared to food secure, individuals with food insecurity would have higher 24-h energy expenditure (EE[kcal/d]) and a 24-h respiratory quotient (RQ[ratio]). Subsequently, we explored hormones involved in appetite regulation, substrate oxidation, and EE. METHODS: One hundred-thirteen non-diabetic healthy participants (75M; Age 40±12 [years]; BMI 30±8 [kg/m(2)]) were included in this analysis. Participants completed the Food Security Short Form, a DXA scan, and spent 24 hours in a human respiratory chamber following a weight maintaining diet. RESULTS: Compared to individuals with food security, participants with food insecurity had no difference in 24-h EE. However, they had higher carbohydrate oxidation rates (p = 0.03), and lower lipid oxidation rates (p = 0.02), resulting in higher 24-h RQ (p

Background Disability is common following critical illness, impacting the quality of life of survivors, and is difficult to measure. ‘Participation’ can be quantified as involvement in life outside of their home requiring movement from their home to other locations. Participation restriction is a key element of disability, and following critical illness, participation may be diminished. It may be possible to quantify this change using pre-existing smartphone data. Objectives The feasibility of extracting location data from smartphones of survivors of intensive care unit (ICU) admission and assessing participation, using location-based outcomes, during recovery from critical illness was evaluated. Methods Fifty consecutively admitted, consenting adult survivors of non-elective admission to ICU of greater than 48-h duration were recruited to a prospective observational cohort study where they were followed up at 3 and 6 months following discharge. The feasibility of extracting location data from survivors' smartphones and creating location-derived outcomes assessing participation was investigated over three 28-d study periods: pre-ICU admission and at 3 and 6 months following discharge. The following were calculated: time spent at home; the number of destinations visited; linear distance travelled; and two ‘activity spaces’, a minimum convex polygon and standard deviation ellipse. Results Results are median [interquartile range] or n (%). The number of successful extractions was 9/50 (18%), 12/39 (31%), and 13/33 (39%); the percentage of time spent at home was 61 [56–68]%, 77 [66–87]%, and 67 [58–77]% (P = 0.16); the number of destinations visited was 34 [18–64], 38 [22–63], and 65 [46–88] (P = 0.02); linear distance travelled was 367 [56–788], 251 [114–323], and 747 [326–933] km over 28 d (P = 0.02), pre-ICU admission and at 3 and 6 months following ICU discharge, respectively. Activity spaces were successfully created. Conclusion Limited smartphone ownership, missing data, and time-consuming data extraction limit current implementation of mass extraction of location data from patients’ smartphones to aid prognostication or measure outcomes. The number of journeys taken and the linear distance travelled increased between 3 and 6 months, suggesting participation may improve over time.

We aimed to compare obstetric and perinatal outcomes of in vitro fertilization (IVF) pregnancies following fresh and frozen embryo transfer (FET). This was a historic cohort of deliveries between November 2008 and January 2020 at a single university hospital, in which each fresh transfer IVF pregnancy was matched to a FET pregnancy by the same woman (1:1 ratio). We included live singleton deliveries (24 weeks of gestation) and excluded pregnancies following egg donation. The primary outcome was birthweight, and secondary outcomes were small for gestational age (SGA) neonates and preterm birth (PTB). A total of 107 fresh transfer pregnancies were matched to 107 FET pregnancies, in the same women. Mean maternal age was lower in the fresh transfer group compared to the FET group (30.4 vs. 32.5 years, p0.001). A higher rate of nulliparity was noted in fresh transfer pregnancies (64.5% vs. 12.1%, p0.001). Mean birthweight was non-significant between the groups (p = 0.13), and the rates of low birthweight and small for gestational age neonates did not differ between the groups. Preterm deliveries occurred in 10.3% and 9.3% of fresh transfer and FET pregnancies respectively, p = 0.79. On multivariate linear regression analysis, the type of embryo transfer-FET or fresh-was not independently associated with birthweight, after adjustment for women's age, nulliparity, and BMI. IVF pregnancies following fresh and FET entailed the same obstetric and perinatal outcomes when compared in the same women.

In a multicenter, retrospective analysis of 435 patients with refractory COVID-19 placed on V-V ECMO, cannulation by a single, dual-lumen catheter with directed outflow to the pulmonary artery was associated with lower inpatient mortality.To determine if a cannulation method for venovenous extracorporeal membrane oxygenation (V-V ECMO) is related to patient outcome.A retrospective, multicenter study of adult patients (≥18 years old) placed on V-V ECMO for severe respiratory failure due to COVID-19 between March 1, 2020, to April 30, 2021. Patients were divided into the following three groups based on the initial cannulation method: (1) femoral vein-femoral vein or femoral vein-internal jugular vein (dual-site, C-DS), (2) single, dual-lumen cannula in internal jugular vein with tip positioned in the pulmonary artery (C-PA), and (3) single, dual-lumen cannula in internal jugular vein with tip positioned in the inferior vena cava (C-IVC). The primary outcome was in-hospital mortality assessed by a time-to-event analysis.Overall, 435 patients from 17 centers comprised the study cohort. C-DS was performed in 247 (57%, age: 49, IQR:39-57 years; 30% female) cases, 99 (23%, age: 53, IQR: 42-59 years; 26% female) received C-PA, and 89 (20%) patients got C-IVC (age: 46, IQR 35-54; 33% female). At 90-days, in-hospital mortality was 60% (C-DS), 41% (C-PA), and 61% (C-IVC), p = 0.06. After adjustment for clinical characteristics, the likelihood of in-hospital mortality in comparison to C-DS, was lower with C-PA (aHR: 0.52, 95%CI 0.32-0.85, p = 0.009) and similar with C-IVC (aHR: 0.96, 95%CI 0.63-1.47, p = 0.86).Catheter-directed flow into the PA bypassing the right ventricle with a single dual-lumen cannula is associated with reduced mortality during V-V ECMO for COVID-19. These findings are limited by residual confounding and site-clustering. Further investigation is urgently warranted with randomized studies.

Thoracic aortic aneurysm and dissection are complex diagnoses that require management by multidisciplinary providers using a variety of medical therapies, surgical interventions, and lifestyle modifications. Pharmacological agents, such as β-blockers (atenolol) and angiotensin II type 1 receptor blockers (losartan), have been mainstay treatments for several years, and research from the past decade has continued to evaluate these and other medication classes to further improve patient morbidity and mortality. Combination β- and renin-aldosterone-angiotensin blockade, statins, metformin, antioxidants, and vitamins have been evaluated as therapeutics in both thoracic and abdominal aortic aneurysms, as well as the effects of various antibiotics (ie, fluoroquinolones and tetracyclines) and benefits of lifestyle modifications (eg, diet and exercise) and enhanced patient-centered care and treatment adherence. In addition, as our understanding of the genetic, biochemical, and pathophysiological mechanisms behind these diseases expands, so do potential targets for future therapeutic research (eg, interleukins, matrix metalloproteases, and mast cells). This review incorporates the major meta-analyses, systematic and generalized reviews, and clinical trials published from 2010 through 2021 that focus on these topics in thoracic aortic aneurysms (and abdominal aneurysms when thoracic literature is scarce). Several key ongoing clinical trials, case studies, and in vivo/in vitro studies are also mentioned. Furthermore, we discuss current gaps in the literature and the abundance of clinical evidence for some interventions in abdominal aneurysms with few thoracic correlates, thus indicating a need for investigation of these subjects in the latter.

Pregnancy-associated aortic dissection (AD) is a rare event, with an incidence of 0.0004% per pregnancy. The work of the Aortic Dissection Collaborative identified pregnancy-associated AD as a high-priority topic, despite its rarity. The Pregnancy Working Group, which included physicians and patient stakeholders, performed a systematic literature review of pregnancy-associated AD from 1960 to 2021 and identified 6,333 articles through PubMed, OVID MEDLINE, Cochrane, Embase, CINAHL and Web of Science. The inclusion criterion was AD in pregnant populations and exclusion criteria were case reports, conference abstracts, and languages other than English. Assessment of full-text articles for eligibility after removal of duplicates from all databases yielded 68 articles to be included in the final review. Topics included were timing of AD in pregnancy, type of AD, and management considerations of pregnancy-associated AD. The Pregnancy Working Group identified gaps in knowledge and future areas of research for pregnancy-associated AD, including clinical management, mental health outcomes post AD, reproductive and genetic counseling, and contraception after AD. Future collaborative projects could be a multicenter, international registry for all pregnancy-associated AD to refine the risk factors, best practice and management of AD in pregnancy. In addition, future mixed methodology studies may be useful to explore social, mental, and emotional factors related to pregnancy-associated AD and to determine support groups' effect on anxiety and depression related to these events in the pregnancy and postpartum period.

Telemedicine uses telephone-based or any form of digital communication for remote clinical services. It has been a field of interest for the last century, with broader implementation of telemedicine technologies during the last 25 years. The COVID-19 pandemic was an impetus for the adoption of these technologies globally across all health care services, including patient care, surgical practice, and workflow. As part of the patient engagement work in the Aortic Dissection Collaborative, this topic was identified as an important patient-centered research topic. Telemedicine has been adopted increasingly in vascular surgery; however, there is little evidence on appropriate use of these technologies pertaining to treating patients with aortic dissection or aortopathy in general. This landscape review summarizes the uses of telemedicine applications pre and post pandemic in medicine and vascular surgery, with a particular focus on uses in aortopathy. Using common resource databases, we identified articles related to the history of telemedicine, its current utilization, and application to vascular surgery and/or aortopathy. We briefly review the history of telemedicine and illustrate a range of applications in medicine before the pandemic, along with its rapid uptake globally during the COVID-19 pandemic. The enablers and barriers to using telemedicine are explored, although as a whole there is satisfaction with its integration among patients and providers. To address these, we offer recommendations to address future research as it pertains to telemedicine technologies in aortic dissection.

Although the topics of surgical techniques and medical therapies have been widely studied in aortic dissection (AD), studies examining the short- and long-term impact of this event on mental health are largely lacking. Many of the studies have used the 36-Item Short Form Survey at variable time points after the event. However, AD as medical trauma has a complex impact on a person's identity. Its implications for emotional, mental, social, existential, and self-concept could be explored more robustly. This topic was identified as a topic of interest by the AD Collaborative. The AD Collaborative Mental Health Working Group was formed and performed a landscape review to summarize current literature surrounding quality of life research in those who have experienced AD, identify gaps in knowledge, and to outline future research questions.

Aortic dissection confers high mortality and morbidity rates despite advances in treatment, impacts quality of life, and contributes immense burden to the healthcare system globally. Efforts to prevent aortic dissection through screening and management of modifiable risk factors and early detection of aneurysms should incorporate genomic information, as it is integral to stratifying risk. However, effective integration of genomic-guided risk assessment into clinical practice will require addressing implementation barriers that currently permeate our healthcare systems. The Aortic Dissection Collaborative was established to define aortic dissection research priorities through patient engagement. Using a collaborative patient-centered feedback model, our Genomic Medicine Working Group identified related research priorities that could be investigated by pragmatic interventional studies aimed at aortic dissection prevention, utilization of genomic information to improve patient outcomes, and access to genomic medicine services. Further research is also needed to identify the genomic, lifestyle, and environmental risk factors that contribute to aortic dissection so these data can be incorporated into future comparative effectiveness studies to prevent aortic dissection.

Understanding what matters most to patients can help guide research in a direction that is best situated to provide evidence that is responsive to their core concerns. This can better inform the treatment decision-making process for patients and their physicians. The Aortic Dissection (AD) Collaborative built a collaborative AD research infrastructure involving patients and other stakeholders to facilitate patient-centered outcomes research training, support, and networking among those affected by AD. Two surveys and semi-structured interviews were conducted between January and October 2020 to gather information from people with and at risk for AD and their family members to better understand their experiences and needs. Discussion of survey and interview results were then articulated as seven key topics for future research to meet the needs of the AD community. Working groups were assembled to address each of the key topics. The groups conducted landscape reviews that were focused on providing guidance for future research that directly addresses the needs identified by the AD community. Recommendations for future research generated by the working groups were compiled by the Aortic Dissection Collaborative. From these recommendations, the Aortic Dissection Collaborative advisors and stakeholders identified high-priority research questions. The research questions form the basis for a third survey, disseminated to the Virtual Research Network between November 2021 and February 2022. Final analysis of the survey will identify top ranked research questions and assess willingness to participate. These results will inform the development of future patient-centered outcomes research and comparative effectiveness research proposals.

Coronavirus disease 2019 (COVID-19) is characterized by striking dysregulation of the immune system, with evidence of hyperinflammation, an impaired induction of interferons, and delayed adaptive immune responses. In addition to dysfunctional immune responses, thrombosis is a hallmark of severe COVID-19. Because traditional anticoagulation strategies are associated with increased bleeding, novel strategies that address both the immune and thrombotic dysfunction associated with COVID-19 would be of tremendous benefit. In this commentary, we discuss the unique properties of low dose naltrexone (LDN) which could be leveraged to reduce the immune-mediated thrombotic complications in COVID-19. Mechanistically, LDN can blunt innate immune responses and Toll-like receptor (TLR) signaling, reducing interleukin1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interferon (IFN) levels. Because of the immune-mediated thrombotic mechanisms that underlie COVID-19, we hypothesize that the immune-modulating and known pharmacologic properties of LDN could be leveraged as a novel therapeutic strategy in COVID-19.

Purpose The purpose of this study was to investigate outcomes following arthroscopic elbow contracture release to describe the use of arthroscopy for improvement in extension/flexion and pronation/supination arcs of motion at a single institution for degenerative and posttraumatic etiologies. Methods Consecutive arthroscopic elbow arthrolysis performed between 2003 and 2015 were retrospectively reviewed. Basic patient demographics, indications for surgery, preoperative and postoperative elbow range of motion, postoperative patient outcome score, and all complications were recorded and analyzed. Results Fifty-two patients were included with an average follow-up of 5.1 years (range 1.4 to 9.4). Severe contractures made up 50% of cases, followed by 23% moderate, and 27% mild. Average extension/flexion for the post-traumatic group (n = 30) increased by 63° ± 31 and by 29° ± 24 for the degenerative group (n = 22). Average gain in pronosupination was 38° ± 62 in the post-traumatic group and 13°±23 in the degenerative group. Postoperative DASH scores were 17.5 ± 18.4 for post-traumatic cases and 12.8 ± 19.3 for degenerative cases. Conclusion Arthroscopic elbow contracture release is an effective intervention for degenerative and post-traumatic elbow contracture for both flexion/extension and pronosupination contracture. Furthermore, a two-stage release should be considered when both flexion and pronosupinaton contractures are present. Level of Evidence IV, case series, treatment study

BACKGROUND AND OBJECTIVES: Performing adequately powered clinical trials in pediatric diseases, such as SLE, is challenging. Improved recruitment strategies are needed for identifying patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Electronic health record algorithms were developed and tested to identify children with SLE both with and without lupus nephritis. We used single-center electronic health record data to develop computable phenotypes composed of diagnosis, medication, procedure, and utilization codes. These were evaluated iteratively against a manually assembled database of patients with SLE. The highest-performing phenotypes were then evaluated across institutions in PEDSnet, a national health care systems network of >6.7 million children. Reviewers blinded to case status used standardized forms to review random samples of cases (n=350) and noncases (n=350). RESULTS: Final algorithms consisted of both utilization and diagnostic criteria. For both, utilization criteria included two or more in-person visits with nephrology or rheumatology and ≥60 days follow-up. SLE diagnostic criteria included absence of neonatal lupus, one or more hydroxychloroquine exposures, and either three or more qualifying diagnosis codes separated by ≥30 days or one or more diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 100% (95% confidence interval [95% CI], 99 to 100), specificity was 92% (95% CI, 88 to 94), positive predictive value was 91% (95% CI, 87 to 94), and negative predictive value was 100% (95% CI, 99 to 100). Lupus nephritis diagnostic criteria included either three or more qualifying lupus nephritis diagnosis codes (or SLE codes on the same day as glomerular/kidney codes) separated by ≥30 days or one or more SLE diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 90% (95% CI, 85 to 94), specificity was 93% (95% CI, 89 to 97), positive predictive value was 94% (95% CI, 89 to 97), and negative predictive value was 90% (95% CI, 84 to 94). Algorithms identified 1508 children with SLE at PEDSnet institutions (537 with lupus nephritis), 809 of whom were seen in the past 12 months. CONCLUSIONS: Electronic health record–based algorithms for SLE and lupus nephritis demonstrated excellent classification accuracy across PEDSnet institutions.

Reduced heart rate variability (HRV) in response to stress is a biomarker of emotion dysregulation (ED) and is related to posttraumatic stress disorder (PTSD), yet less is known about its role with dissociation in trauma-exposed adults. The goals of the current study were to examine unique patterns of associations between ED, dissociation, and PTSD with HRV at 15, 30, and 45 minutes (T1, T2, T3) following an acute psychosocial stressor task in a sample of 49 trauma-exposed, urban-dwelling Black women. Associations with baseline psychophysiology measures were also examined. ED and dissociation were assessed using self-report; PTSD was determined using a semi-structured interview. Heart rate (HR) and HRV, indexed with low frequency/high frequency (LF/HF) ratio and respiratory sinus arrhythmia (RSA), were measured with electrocardiogram recordings. ED and dissociation were positively correlated with LF/HF ratio at T3 (p

Carpal tunnel release (CTR) is a surgical treatment option for patients with carpal tunnel syndrome (CTS) symptoms that are unresponsive to conservative treatment. Most patients experience symptomatic relief after CTR regardless of the surgical technique. However, direct comparisons of the safety and effectiveness between CTR surgical techniques are limited. The purpose of this randomized controlled trial is to compare the safety and effectiveness of CTR with ultrasound guidance (CTR-US) versus mini-open CTR (mOCTR) in subjects with symptomatic CTS.TUTOR (Trial of Ultrasound guided CTR versus Traditional Open Release) is a randomized controlled trial in which 120 subjects at up to 12 sites in the United States will be randomized (2:1) to receive CTR-US or mOCTR. The primary endpoint of the study is the percentage of patients who return to normal daily activities within 3 days of the procedure. Secondary endpoints of the study are median time to return to normal daily activities, percentage of patients who return to work within 3 days of the procedure, median time to return to work, Boston Carpal Tunnel Questionnaire Symptom Severity Scale (BCTQ-SSS) change score at 3 months, BCTQ Functional Status Scale (BCTQ-FSS) change score at 3 months, Numeric Pain Scale change score at 3 months, EuroQoL-5 Dimension 5-Level (EQ-5D-5L) change score at 3 months, and the incidence of device- or procedure-related adverse events at 3 months. Patient follow-up in this trial will continue for 1 year.This study was approved by a central institutional review board and ongoing trial oversight will be provided by a data safety monitoring board (DSMB). The authors intend to report the results of this trial at medical conferences and peer-reviewed journals. The outcomes of TUTOR will have important clinical and economic implications for all stakeholders involved in treating patients with CTS.ClinicalTrials.gov (https://clinicaltrials.gov): NCT05405218.1.

Objective The aim of the study was to determine the response rate to a mixed-mode survey using email compared with that to a paper survey in survivors of critical illness. Design This is a prospective randomised controlled trial. Setting The study was conducted at a single-centre quaternary intensive care unit (ICU) in Adelaide, Australia. Participants Study participants were patients admitted to the ICU for ≥48 h and discharged from the hospital. Interventions The participants were randomised to receive a survey by paper (via mail) or via online (via email, or if a non-email user, via a letter with a website address). Patients who did not respond to the initial survey received a reminder paper survey after 14 days. The survey included quality of life (EuroQol-5D-5L), anxiety and depression (Hospital Anxiety and Depression Scale), and post-traumatic symptom (Impact of Event Scale-Revised) assessment. Main outcome measures Survey response rate, extent of survey completion, clinical outcomes at different time points after discharge, and survey cost analysis were the main outcome measures. Outcomes were stratified based on follow-up time after ICU discharge (3, 6, and 12 months). Results A total of 239 patients were randomised. The response rate was similar between the groups (mixed-mode: 78% [92/118 patients] vs. paper: 80% [97/121 patients], p = 0.751) and did not differ between time points of follow-up. Incomplete surveys were more prevalent in the paper group (10% vs 18%). The median EuroQol-5D-5L index value was 0.83 [0.71–0.92]. Depressive symptoms were reported by 25% of patients (46/187), anxiety symptoms were reported by 27% (50/187), and probable post-traumatic stress disorder was reported by 14% (25/184). Patient outcomes did not differ between the groups or time points of follow-up. The cost per reply was AU$ 16.60 (mixed-mode) vs AU$ 19.78 (paper). Conclusion The response rate of a mixed-mode survey is similar to that of a paper survey and may provide modest cost savings.

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1. Sequence analysis identifies gain-of-function somatic mutations in GNA11 or GNAQ in CTNNB1-mutant aldosterone-producing adenomas. Most patients with these mutations presented during puberty, pregnancy or menopause, with elevated LHCGR expression.

Hematology analyzers capable of performing complete blood count (CBC) have lagged in their prevalence at the point-of-care. Sight OLO (Sight Diagnostics, Israel) is a novel hematological platform which provides a 19-parameter, five-part differential CBC, and is designed to address the limitations in current point-of-care hematology analyzers using recent advances in artificial intelligence (AI) and computer vision. Accuracy, repeatability, and flagging capabilities of OLO were compared with the Sysmex XN-Series System (Sysmex, Japan). Matrix studies compared performance using venous, capillary and direct-from-fingerprick blood samples. Regression analysis shows strong concordance between OLO and the Sysmex XN, demonstrating that OLO performs with high accuracy for all CBC parameters. High repeatability and reproducibility were demonstrated for most of the testing parameters. The analytical performance of the OLO hematology analyzer was validated in a multicenter clinical laboratory setting, demonstrating its accuracy and comparability to clinical laboratory-based hematology analyzers. Furthermore, the study demonstrated the validity of CBC analysis of samples collected directly from fingerpricks.

There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes.

Laparoscopic sacrohysteropexy (LSH), sacrocolpopexy (LSC) and ventral rectopexy (LVR) with mesh are advocated for surgical treatment of pelvic and rectal prolapse. Our study aims at showing the feasibility of concomitant laparoscopic prolapse repair by comparing perioperative and long-term outcomes of LSH or LSC with and without LVR. This is a retrospective study carried out on 348 women operated on between July 2009 and July 2019. Patients were divided into four groups: (1) LSH only, (2) LSC only, (3) LSH + LVR and (4) LSC + LVR. POP-Q scores and satisfaction questionnaires were recorded at baseline and then annually. Outcomes were defined as subjective failure (vaginal/rectal prolapse symptoms), objective failure (prolapse to/beyond the hymen, full thickness rectal prolapse) or retreatment for prolapse. Complications were collected and graded according to the Clavien-Dindo classification. Three hundred forty-eight women underwent laparoscopic repair for pelvic and rectal prolapse (219, 44, 66 and 19 in group 1, 2, 3 and 4, respectively). Median follow-up was 24 (4–174) months. Success rate for both rectal and pelvic prolapse was 90.2%. Recurrence rates were not significantly different between the groups (12.3%, 6.8%, 9.1% and 10.5% for groups 1, 2, 3 and 4, respectively). Significant improvement was noticed in satisfaction questionnaires in all groups. There was no difference in perioperative and late complications. The combined laparoscopic procedure appears to be safe and efficient in treating pelvic and rectal prolapse. Appropriate patient selection and available surgical expertise should determine whether to perform these procedures combined or separately.

OBJECTIVE To examine if older age (>70 years) should be a relative contraindication for heart transplantation, we evaluated the characteristics and outcomes of patients with age ≥70 years listed for heart transplantation; and whether post-transplantation survival was inferior to younger counterparts. DESIGN Retrospective cohort analysis. SETTING The scientific registry of transplant recipients (SRTR). PARTICIPANTS Adults (≥18 years) listed for heart transplantation in the SRTR between 2000 and 2018. INTERVENTIONS Heart transplantation. MEASUREMENTS Characteristics and outcomes were compared for adults ≥70 years and

Background Recently, three updated guidelines for post‐polypectomy colonoscopy surveillance (PPCS) have been published. These guidelines are based on a comprehensive summary of the literature, while some recommendations are similar, different surveillance intervals are recommended after detection of specific types of polyps. Aim In this review, we aimed to compare and contrast these recommendations. Methods The updated guidelines for PPCS were reviewed and the recommendations were compared. Results For patients with 1–4 adenomas

Automated information extraction might be able to assist with the collection of stroke key performance indicators (KPI). The feasibility of using natural language processing for classification-based KPI and datetime field extraction was assessed. Using free-text discharge summaries, random forest models achieved high levels of performance in classification tasks (area under the receiver operator curve 0.95-1.00). The datetime field extraction method was successful in 29 of 43 (67.4%) cases. Further studies are indicated.

Purified cannabinoids have been shown to prevent proliferation and induce apoptosis in colorectal carcinoma cell lines. To assess the cytotoxic effect of cannabinoid extracts and purified cannabinoids on both colorectal polyps and normal colonic cells, as well as their synergistic interaction. Various blends were tested to identify the optimal synergistic effect. Methods: Biopsies from polyps and healthy colonic tissue were obtained from 22 patients undergoing colonic polypectomies. The toxicity of a variety of cannabinoid extracts and purified cannabinoids at different concentrations was evaluated. The synergistic effect of cannabinoids was calculated based on the cells’ survival. Isolated cannabinoids illustrated different toxic effects on the viability of cells derived from colorectal polyps. THC-d8 and THC-d9 were the most toxic and exhibited persistent toxicity in all the polyps tested. CBD was more toxic to polypoid cells in comparison to normal colonic cells at a concentration of 15 µM. The combinations of the cannabinoids CBDV, THCV, CBDVA, CBCA, and CBGA exhibited a synergistic inhibitory effect on the viability of cells derived from colon polyps of patients. Isolated cannabinoid compounds interacted synergistically against colonic polyps, and some also possessed a differential toxic effect on polyp and adjacent colonic tissue, suggesting possible future therapeutic value.

To study the changes in acute otitis media (AOM) pediatric emergency department (PED) visits and pediatric admission before and during the first coronavirus disease 2019 (COVID-19) year.Retrospective case review.Secondary care center.Children younger than 18 years with all-cause and AOM-related PED visits and pediatric admissions for 3 years (March 1, 2018-January 28, 2021) were identified. Children were categorized according to age (0-2, 2-6, and 6-18 yr) and their date of presentation: pre-COVID-19 (yearly average of visits/admissions during the 2 prepandemic years: March 1, 2018-February 28, 2019 and March 1, 2019-February 29, 2020) or COVID-19 year (visits/admissions between March 1, 2020-February 28, 2021).Pre- and post-COVID-19 emergence, alternating lockdowns, kindergarten and school closures, and increased hygiene measures.Post- versus pre-COVID-19 AOM PED visit and pediatric admission incidence rate ratios (IRRs), using a generalized estimating equation model with a negative binomial regression calculation, while controlling for monthly fluctuations.Annual AOM visits/admissions during the pre-COVID-19 and COVID-19 years were 517 and 192 and 256 and 94, respectively (p0.05 for both). For children aged 0 to 2 years, AOM visits/admissions significantly decreased during the first COVID-19 year, compared with the pre-COVID years (β = -1.11 [IRR, 0.33; 95% confidence interval [CI], 0.26-0.42; p0.005] and β = -1.12 [IRR, 0.33; 95% CI, 0.25-0.42; p0.005]). Relatively to all-cause of children aged 0 to 2 years, AOM visits/admissions decreased during the first COVID-19 year versus the pre-COVID-19 years (β = -2.14 [IRR, 0.12; 95% CI, 0.08-0.17; p0.005] and β = -1.36 [IRR, 0.26; 95% CI, 0.23-0.29; p0.005]) and had monthly fluctuations coinciding with the lockdown/relaxation measures. For children aged 2 to 6 years, the reduction in AOM admissions was significant (β = -1.70, IRR, 0.18; 95% CI, 0.09-0.37; p0.005). No significant differences were observed for children aged 6 to 18 years because of the small sample size.Pediatric AOM burden substantially decreased during the first COVID-19 year.

Background We aimed to assess the correlation between ovarian hyperstimulation syndrome (OHSS) in the early course of in vitro fertilization (IVF) pregnancies and obstetric outcomes. Methods We identified records of patients admitted due to OHSS following IVF treatment at our institution between 2008 and 2020. Cases were included if pregnancy resulted in a live singleton delivery (OHSS group). OHSS cases were matched at a 1:5:5 ratio with live singleton deliveries following IVF with fresh embryo transfer (fresh transfer group) and frozen embryo transfer (FET group), according to maternal age and parity. Computerized files were reviewed, and maternal, obstetric and neonatal outcomes compared. Results Overall, 44 OHSS cases were matched with 220 fresh transfer and 220 FET pregnancies. Patient demographics were similar between the groups, including body mass index, smoking and comorbidities. Gestational age at delivery, the rate of preterm births, preeclampsia and cesarean delivery were similar between the groups. Placental abruption occurred in 6.8% of OHSS pregnancies, 1.4% of fresh transfer pregnancies and 0.9% of FET pregnancies (p=0.02). On post-hoc analysis, the rate of placental abruption was significantly higher in OHSS pregnancies, compared with the two other groups, and this maintained significance after adjustment for confounders. Birthweights were 3017 ± 483, 3057 ± 545 and 3213 ± 542 grams in the OHSS, fresh transfer and FET groups, respectively (p=0.004), although the rate of small for gestational age neonates was similar between the groups. Conclusions OHSS in the early course of IVF pregnancies is associated with an increased risk of placental abruption.

Poor communication and lack of standardized handover practices contribute to adverse events. Intensive care organizations recommend standardized, structured written and verbal handover. Investigate the effectiveness of, and barriers to, Intensive Care Unit (ICU) patient handover at ward transfer. Screen for patient safety incidents related to poor handover and improve practice where deficiencies are identified. A survey of ward doctors about specific ICU to ward transfers and online surveys ascertaining opinions of handover processes were sent to ward-based and ICU doctors at a large, adult, university affiliated, Australian quaternary hospital. We delivered departmental education and created then publicized a new electronic ICU transfer summary. The summary included a mandatory tick-box to confirm verbal handover completion. Surveys re-assessing practice were then performed. Forty ward-based doctors were surveyed about specific transfers, with 7 (18%) instances of issues related to handover identified. Eighty-seven ward doctors completed the pre-interventions survey; 48 (55%) were aware of the existing written transfer summary. Post-interventions, 47 (75%) of 63 ward doctor responders were aware of it (p < 0.05). Pre-interventions, 14 (16%) ward doctors rated ICU handovers as excellent or good, rising to 21 (34%) post-interventions (p < 0.05). Thirty-nine ICU doctors completed the pre-interventions survey; 5 (13%) rated ICU to ward handover as excellent or good, rising to 9 (35%) when re-surveyed (p = 0.097). The perceived quality of ICU to ward handover improved after our interventions. However, ICU doctors continue to transfer patients without verbally handing over, with contacting the ward team representing a significant handover barrier.

Variants in SMAD4 or BMPR1A cause juvenile polyposis syndrome, a rare autosomal dominant condition characterized by multiple gastrointestinal hamartomatous polyps. A phenotype of attenuated adenomatous polyposis without hamartomatous polyps is rare.We describe a retrospective cohort of individuals with SMAD4 or BMPR1A heterozygous germline variants, having ≥10 cumulative colorectal adenomas and/or colorectal cancer without hamartomatous polyps. All individuals had multigene panel and duplication/deletion analysis to exclude other genetic syndromes.The study cohort included 8 individuals. The pathogenic potential of the variants was analyzed. Variants detected included 4 missense variants, 1 nonsense variant, 1 splice site variant, and 2 genomic deletions. Features of pathogenicity were present in most variants, and cosegregation of the variant with polyposis or colorectal cancer was obtained in 7 of the 8 families. Three of 8 individuals had colorectal cancer (age less than 50 years) in addition to the polyposis phenotype. Two individuals had extraintestinal neoplasms (pancreas and ampulla of Vater).The clinical phenotype of SMAD4 and BMPR1A variants may infrequently extend beyond the classical juvenile polyposis syndrome phenotype. Applying multigene panel analysis of hereditary cancer-related genes in individuals with unexplained polyposis can provide syndrome-based clinical surveillance for carriers and their family members.