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Standardized letters of recommendation (SLOR) are hypothesized to decrease bias and provide consistent domains for evaluation. However, their ability to differentiate among applicants is unknown. The utilization and functionality of SLOR and the impact of SLOR domain rating on matching for colon and rectal surgery (CRS) residency applicants have yet to be assessed.Descriptive statistics and bivariate analysis were employed. Applicants were categorized into 3 groups; Top-tier(TT): applicants rated 100% Excellent/Very Good; Mid-Tier(MT) applicants rated 80-99% Excellent/Very Good; and Non-Top Tier(NTT) applicants rated80% Excellent/Very Good.University of Hospitals Cleveland Medical Center.SLORs submitted to a single colorectal surgery residency in 2019 were analyzed RESULTS: A total of 101 applicants were included, 54 (53.5%) of the applicants were male. 75 (74.2%) applicants who applied to our residency matched into a CRS residency, compared to the national rate of 66%. Of the 101 applicants with SLOR, 54 (53.5%) were categorized as TT, 26 (25.7%) as MT, and 21(20.8%) as NTT. The univariable analysis demonstrated a statistically significant difference in research experience (p=0.029) and match status (p=0.01) between applicant tiers. There were no statistically significant differences between applicant-tier and demographics, foreign medical graduates (FMG), H-indices, ABSITE scores, type of residency, preliminary year, completing an unaccredited CRS, and applicants with an additional degree. On multivariable analysis age (OR=0.65; CI=0.48-0.87) and FMG applicants (OR=0.05; CI=0.01-0.44) were inversely associated with successfully matching. Compared to TT applicants, MT (OR=0.07; CI=0.01-0.57) and NTT (OR=0.04; CI=0.01-0.34) applicants were inversely associated with a successful match. Individuals who completed research prior to residency but after medical school was associated with successfully matching (p=0.009).The presence of MT and NTT ratings is associated with failure to match and may represent an area of concern for CRS programs rather than a tool to discern differences between candidates.

To describe the clinical and laboratory outcomes of infants with subcutaneous fat necrosis of the newborn (SCFN) and propose a care algorithm.This single-center, retrospective study of infants diagnosed with SCFN at AnnRobert H. Lurie Children's Hospital of Chicago from 2009 to 2019.Of 32 infants who met inclusion criteria, most were born full-term (84%), born via cesarean section (58%), had normal weight for gestational age (69%), and experienced delivery complications (53%). Twenty-nine infants (91%) had calcium drawn, and all had hypercalcemia. Three infants developed clinical symptoms of hypercalcemia, two required hospital admission, two developed nephrocalcinosis, and one developed acute kidney injury. The majority of infants (62%) had a peak ionized calcium between 1.5 and 1.6 mmol/L. No infants with peak ionized calcium less than 1.5 mmol/L developed complications of hypercalcemia. Most patients were diagnosed with hypercalcemia (86%) and demonstrated peak ionized calcium levels (59%) within the first 28 days of life. No patients developed hypercalcemia after 3 months of age.Hypercalcemia occurred in 100% of infants who had laboratory monitoring. We recommend obtaining an initial ionized calcium level when SCFN is suspected, and monitoring for the first 3 months of life if hypercalcemia has not been detected. In patients with asymptomatic hypercalcemia less than 1.5 mmol/L, there appears to be low likelihood of related complications. For symptomatic, markedly elevated (1.6 mmol/L), or persistently elevated levels (6 months) we suggest coordinated care with endocrinology or nephrology, consider hospitalization, and urinary system ultrasound.

The history of pouch surgery is rooted in surgical innovation to improve quality of life in patients requiring surgical extirpation of the colon and rectum. From the early straight ileoanal anastomosis to the continent ileostomy to the modern ileal pouch anal anastomosis (IPAA), techniques have evolved in response to pitfalls in design. Optimal IPAA design and construction have changed in response to functional outcomes. Nowadays, restorative proctocolectomy with IPAA is the optimal treatment for patients with ulcerative colitis or familial adenomatous polyposis. The J-pouch with stapled anastomosis has become the preferred procedure. Historical configurations and technical pearls, as described in this article, should be considered by surgeons who regularly care for patients requiring ileal pouch surgery.

Perioperative hyperglycemia is a risk factor in surgical patients. Complications, including infection and mortality, are associated with hyperglycemia in both diabetic and nondiabetic patients. Stress hyperglycemia results in a state of insulin resistance. Insulin administration has been shown to reduce the complications associated with hyperglycemia. Glycemic targets provide goals for individualized treatment of hyperglycemia in surgical patients in the preoperative, intraoperative, and postoperative periods.

The aim of this study was to review bariatric procedure outcomes among patients with Prader-Willi syndrome (PWS), melanocortin 4 receptor (MC4R) mutations, Bardet-Biedl syndrome, and hypothalamic obesity.Systematic published literature review used the following search terms: "Prader-Willi syndrome," "Bardet-Biedl syndrome," "hyperphagia," "bariatric surgery," "MC4R"/"melanocortin 4 receptor", "hypothalamic obesity," and "bariatric procedure." Information collected included demographics, genetics, anthropometry, procedure type, outcomes, and complications, with inclusion of case series and clinical reports given the rarity of the disorders. For PWS, postoperative weight-change percentage and BMI up to 14 years following surgery were analyzed using general linear mixed models, with descriptive outcomes for other conditions.A total of 54 publications were identified, with variable follow-up periods for 202 patients (114 with PWS, 43 with MC4R mutations, 7 with Bardet-Biedl syndrome, and 38 with hypothalamic obesity) among bariatric procedures. Weight loss of patients with PWS was greatest within 1 year of surgery, with weight-change percentage not significantly different from 0 at 5 years. Long-term results in other conditions were variable and featured suboptimal weight loss and increased reoperation risk.Bariatric procedures among hyperphagic individuals, including those with PWS, report variable results and outcomes. Benefits of bariatric surgery may be less durable in hyperphagic disorders in comparison with other patients with severe obesity.

Objectives Black youth with type 1 diabetes (T1D) are at heightened risk for suboptimal glycemic control. Studies of neighborhood effects on the health of youth with T1D are limited. The current study investigated the effects of racial residential segregation on the diabetes health of young Black adolescents with T1D. Methods A total of 148 participants were recruited from 7 pediatric diabetes clinics in 2 US cities. Racial residential segregation (RRS) was calculated at the census block group level based on US Census data. Diabetes management was measured via self-report questionnaire. Hemoglobin A1c (HbA1c) information was gathered from participants during home-based data collection. Hierarchical linear regression was used to test the effects of RRS while controlling for family income, youth age, insulin delivery method (insulin pump versus syringe therapy), and neighborhood adversity. Results HbA1c was significantly associated with RRS in bivariate analyses, whereas youth-reported diabetes management was not. In hierarchical regression analyses, whereas family income, age, and insulin delivery method were all significantly associated with HbA1c in model 1, only RRS, age, and insulin delivery method were significantly associated with HbA1c in model 2. Model 2 explained 25% of the variance in HbA1c (P = .001). Conclusions RRS was associated with glycemic control in a sample of Black youth with T1D and accounted for variance in HbA1c even after controlling for adverse neighborhood conditions. Policies to reduce residential segregation, along with improved screening for neighborhood-level risk, hold the potential to improve the health of a vulnerable population of youth.

Restorative proctocolectomy with ileal pouch-anal anastomosis remains the gold standard treatment for patients with ulcerative colitis who desire restoration of intestinal continuity. Despite a significant cancer risk reduction after surgical removal of the colon and rectum, dysplasia and cancers of the ileal pouch or anal transition zone still occur and are a risk even if an anal canal mucosectomy is performed. Surgical care and maintenance after ileoanal anastomosis must include consideration of malignant potential along with other commonly monitored variables such as bowel function and quality of life. Cancers and dysplasia of the ileal pouch are rare but sometimes difficult-to-manage sequelae of pouch surgery.

Context Acylated ghrelin (AG) stimulates appetite and is elevated compared to its unacylated (UAG) counterpart in Prader-Willi syndrome (PWS). GLWL-01 is a selective, reversible inhibitor of ghrelin O-acyltransferase (GOAT), the enzyme that converts UAG into AG. Objective This work aimed to assess the efficacy, pharmacokinetics, pharmacodynamics, and safety of GLWL-01 in the treatment of PWS patients. Methods A double-blind, placebo-controlled, phase 2 crossover study was conducted with 2 active treatment periods of 28 days in 19 patients (aged 16-65 years; body mass index (BMI) ≥ 28) with genetically confirmed PWS. The study took place in 7 hospital-based study centers in the United States and Canada. Patients received placebo or GLWL-01 (450 mg twice daily) orally after lead-in placebo and washout periods. The Hyperphagia Questionnaire for Clinical Trials and Caregiver Global Impression of Change were used to measure reductions in hyperphagia. Plasma concentrations of AG and UAG were evaluated as correlates. Results Treatment resulted in statistically significant differences compared to placebo in plasma AG (P = .0002), UAG (P = .0488), and AG/UAG (P = .0003). GLWL-01 did not statistically significantly reduce hyperphagia-related behavior or bring about changes in global clinical end points, as assessed by caregivers. Anthropometric and clinical parameters correlated with obesity did not statistically significantly change in response to treatment. Less than half of patients reported a treatment-emergent adverse event (TEAE). No deaths, serious adverse events, or severe TEAEs were reported. Conclusion GLWL-01 is safe and well tolerated. Pharmacological parameters confirmed the inhibition of GOAT following administration of GLWL-01. Patients’ eating behaviors, BMI, blood glucose, and total cholesterol, among other similar measures, were not modified.

Context Prader-Willi syndrome (PWS) is a rare neurobehavioral-metabolic disease caused by the lack of paternally expressed genes in the chromosome 15q11-q13 region, characterized by hypotonia, neurocognitive problems, behavioral difficulties, endocrinopathies, and hyperphagia resulting in severe obesity if not controlled. Objective The primary end point was change from baseline in hyperphagia using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Other end points included Global Impression Scores, and changes in body composition, behaviors, and hormones. Methods In DESTINY PWS, a 13-week, randomized, double-blind, placebo-controlled, phase 3 trial, 127 participants with PWS aged 4 years and older with hyperphagia were randomly assigned 2:1 to diazoxide choline extended-release tablet (DCCR) or placebo. Results DCCR did not significantly improve hyperphagia (HQ-CT least-square mean (LSmean) [SE] −5.94 [0.879] vs −4.27 [1.145]; P = .198), but did so in participants with severe hyperphagia (LSmean [SE] −9.67 [1.429] vs −4.26 [1.896]; P = .012). Two of 3 secondary end points were improved (Clinical Global Impression of Improvement [CGI-I]; P = .029; fat mass; P = .023). In an analysis of results generated pre-COVID, the primary (HQ-CT; P = .037) and secondary end points were all improved (CGI-I; P = .015; Caregiver Global Impression of Change; P = .031; fat mass; P = .003). In general, DCCR was well tolerated with 83.3% in the DCCR group experiencing a treatment-emergent adverse event and 73.8% in the placebo group (not significant). Conclusion DCCR did not significantly improve hyperphagia in the primary analysis but did in participants with severe baseline hyperphagia and in the pre-COVID analysis. DCCR treatment was associated with significant improvements in body composition and clinician-reported outcomes.

Context Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy. Objective To evaluate safety and efficacy of intranasal carbetocin in PWS. Design Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up. Setting Twenty-four ambulatory clinics at academic medical centers. Participants A total of 130 participants with PWS aged 7 to 18 years. Interventions Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose. Main outcome measures Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C). Results Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing. Conclusions Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS. Clinical Trials Registration Number NCT03649477

To evaluate weight gain in children post-thyroidectomy and identify predictors.Charts from patients at a tertiary health care facility who underwent total thyroidectomy from 2014 to 2020 were reviewed for Body Mass Index z-scores (BMIz) at the time of thyroidectomy and at 1 and 2-year post-operation intervals. Patient demographic information, comorbidities, pre- and postoperative thyroid stimulating hormone, and postoperative free T4 levels were also extracted. Patients with other known endocrine abnormalities, chronic kidney disease, or without sufficient follow-up were excluded.A total of 56 patients (ages 3-17 years old) met the inclusion criteria (n = 17 Graves' disease; n = 39 presumed cancer). Over the first year, average BMIz significantly increased in patients with Graves' disease (∆BMIz = 0.45 ± 0.77, p = 0.03), Hispanic ethnicity (∆BMIz = 0.43 ± 0.68, p = 0.004), Medicaid/no insurance coverage (∆BMIz = 0.33 ± 0.74, p = 0.038), age13 years at thyroidectomy (∆BMIz = 0.35 ± 0.68, p = 0.016), and persistent postoperative hypothyroidism (∆BMIz = 0.41 ± 0.41, p = 0.012). These changes remained significant after the second year. Age at thyroidectomy correlated negatively with ∆BMIz only after the first year (r = -0.40, p = 0.002). Regression analysis, controlling for Graves' status, persistent postoperative hypothyroidism, and insurance coverage, identified age at thyroidectomy as a significant predictor of ∆BMIz after the first year (b = -0.06, p = 0.004) and Hispanic ethnicity as a significant predictor after the second year (b = 0.60, p = 0.003).A small increase in BMIz post-thyroidectomy was observed across several patient subgroups. Younger age at thyroidectomy and Hispanic ethnicity were associated with increased BMIz in the first 2 years post-thyroidectomy.Level 4- Historically controlled cohort Laryngoscope, 2022.

Aims Patients with heart failure (HF) and their family caregivers commonly experience depressive symptoms associated with low quality of life (QOL) at the individual level. However, there is a lack of knowledge about how QOL and family function are associated with depressive symptoms at the dyad level. The aim of this article is to compare QOL and family function among dyads stratified by depressive symptoms. Methods and results Outpatients with HF and their primary caregivers completed the Beck Depression Inventory-II for depressive symptoms, the Short Form 36 for physical and mental QOL, and the McMaster Family Assessment Device for a family function. Analysis of variance was used to compare QOL and family function among the four dyad groups. A total of 91 dyads were categorized into four groups: neither member having depressive symptoms (43.9%), only the caregiver having depressive symptoms (13.2%), only the patient having depressive symptoms (23.1%), and both members having depressive symptoms (20.9%). Dyads without depressive symptoms had the highest levels of physical and mental QOL among the groups. The dyads with both members having depressive symptoms had the lowest levels of physical and mental QOL (P < 0.001) and the lowest levels of general family functioning, problem-solving ability, and communication ability (P < 0.001). Intermediate levels of QOL were seen in dyads with only one member having depressive symptoms, and a similar pattern of intermediate scores was found in all three subscales of family function. Conclusion Dyads with both members having depressive symptoms may be at greatest risk of having poor QOL and low family functioning.

Prader-Willi syndrome (PWS) is a complex genetic disorder with three molecular classes but clinical ascertainment is based on distinctive features. The prevalence of dysmorphic features was studied in 355 PWS participants (61% deletion, 36% maternal disomy UPD and 3% imprinting defects) from the National Institute of Health PWS Rare Diseases Clinical Research Network. The effect of growth hormone (GH) treatment on growth and dysmorphic features was compared. Among participants, upslanting palpebral fissures were seen in 23%; strabismus in 42%; abnormal dentition in 32%; small hands in 63% and small feet in 70%; hypopigmentation in 30%; striae in 32% and skin picking in 26%. Compared to those with UPD, participants with deletions were found to be heavier (p = 0.002), had smaller head circumference (p = 0.009), higher incidence of a flat occiput (p = 0.005); low anterior hairline (p = 0.04); abnormal dentition (p = 0.009); abdominal striae (p = 0.045), nail abnormalities (p = 0.050), and fair-haired (p < 0.001). Participants in both genetic groups receiving GH were taller (p = 0.005), had larger head circumferences (p = 0.005), and longer hands (p = 0.049). This study suggested that PWS genetic subtypes and GH treatment can influence growth and dysmorphic features that may impact clinical diagnosis of PWS, such as stature, head shape and appearance of the eyes, nose and genitalia.

Introduction: Persons with diabetes and COVID-have higher rates of morbidity and mortality than those without diabetes. Engagement in Diabetes Self-Management Education and Support (DSMES) services may improve diabetes self-management adherence. The purpose of this study was to determine whether COVID-impact and attendance of DSMES services were predictors of diabetes self-management among individuals with T2D during the pandemic. Methods: Participants (N=86) of this cross-sectional survey study were adults with T2D who either had (n=29) or had not (n=57) previously attended at least one DSMES class. The Coronavirus Impact Scale (range 0-24) was used to measure impact of the pandemic on daily life. The Self-Management Profile for Type 2 Diabetes was used to measure overall self-management and subscales for adherence, ease, coping, and importance. Multiple linear regressions were conducted to determine whether COVID-impact and DSMES participation predicted self-management total scores or subscale scores, controlling for age, sex, marital status, financial status, and time since diabetes diagnosis, with separate models for each predictor. Results: Participants were 57±12.3 years; 50% female, and 90% non-Hispanic White. DSMES attendance did not significantly predict subscale or overall scores for self-management. Higher COVID-impact predicted worse self-management adherence (F 3.71, p=0.002) , greater self-management ease (F 3.72, p=0.002) , decreased coping (F 4.65, p Conclusions: Findings underscore the negative impact of the COVID-pandemic on diabetes self-management and highlight the need for interventions to improve self-management practices during times of crisis. Disclosure L.Koonmen: None. T.A.Lennie: None. M.Ickes: None. L.B.Hieronymus: None. J.L.Miller: None. G.Mudd-martin: None. Funding Jonas Nurse Scholars Program, University of Kentucky College of Nursing PhD Dissertation Research Award

Aims The association of delay in seeking medical care to subsequent cardiac events remains unknown in patients with worsening heart failure (HF) symptoms. The aims of this study were to (i) identify factors predicting care-seeking delay and (ii) examine the impact of care-seeking delay on subsequent cardiac rehospitalization or death. Methods and results We studied 153 patients hospitalized with an exacerbation of HF. Potential predictors of delay including demographic, clinical, psychosocial, cognitive, and behavioural variables were collected. Patients were followed for 3 months after discharge to determine time to the first cardiac rehospitalization or death. The median delay time was 134 h (25th and 75th percentiles 49 and 364 h). Non-linear regression showed that New York Heart Association functional class III/IV (P = 0.001), worse depressive symptoms (P = 0.004), better HF knowledge (P = 0.003), and lower perceived somatic awareness (P = 0.033) were predictors of delay time from patient perception of worsening HF to subsequent hospital admission. Cox regression revealed that patients who delayed longer (more than 134 h) had a 1.93-fold higher risk of experiencing cardiac events (P = 0.044) compared to non-delayers. Conclusions Care-seeking delay in patients with worsening HF symptoms was significantly associated with an increased risk of rehospitalization and mortality after discharge. Intervention strategies addressing functional status, psychological state, cognitive and behavioural factors are essential to reduce delay and thereby improve outcomes.

This year’s review of queer theory focuses on recent scholarship about transgender youth. Most of the scholarship reviewed in this chapter defines transgender expansively to include any identifications and/or expressions of gender that trouble dyadic sex-gender ideologies. Additionally, the scholarship reviewed in this chapter evinces a collapse of scholarship and activism by investing in scholarship as activism. Although queer theory is not often heralded for its use in taking a pragmatic approach to social change, the majority of theorists discussed in the chapter do in fact make practical recommendations for justice-oriented social policy and practice changes that would radically improve the lives of transgender youth. Even more, most of the scholars discussed in this chapter are themselves transgender and are committed to creating a world were trans lives can flourish. They resist liberal accommodation models of trans inclusion and instead theorize what meaningful structural change would look like. The chapter is divided into five sections: 1. Introduction: Queer Kids; 2. Queer Gender Now; 3. Queer Youth Now; 4. Transgender Youth In and Out of History; and 5. Conclusion.

Prader-Willi syndrome (PWS) is a complex, multisystem neurodevelopmental disorder affecting approximately 1 in 25,000 live births. PWS is caused by absence of expression of paternally inherited imprinted genes on chromosome 15q11-q13. The syndrome typically occurs due to one of three genetic mechanisms: paternal deletion of involved genes, maternal uniparental disomy, or imprinting center defects. These genetic anomalies lead to well-described clinical phenotype that includes hypotonia, hypothalamic dysfunction, social and behavioral issues, life-threatening hyperphagia, and elevated probability of obesity. Adolescents with PWS are at the highest risk for development of life-threatening obesity due to increased access to food, decreased physical activity, and hyperphagia. Currently, the only treatment for the hyperphagia is environmental control, including locked kitchens and continuous supervision of the affected individual. Caloric intake must be restricted to prevent obesity, which subsequently increases the hunger drive even more. Research and clinical practice have demonstrated that increasing physical activity along with insuring a well-balanced, nutritionally dense diet can improve overall weight control in adolescents with PWS.

Background: Underutilization of operative management of early stage pancreatic cancer is associated with sociodemographic variables, including age, race, facility type, insurance, and education. It is currently unclear how these variables are associated with survival in patients who undergo surgery. Methods: Patients with clinical stage I pancreatic adenocarcinoma were identified within the National Cancer Database (2010–2016). Utilization of surgery and nonoperative management was determined. Nonclinical factors associated with nonoperative management were identified by multivariable analysis. The association between nonclinical factors and survival was assessed in patients who received operative management. Results: A total of 17,833 patients with clinical stage I pancreatic cancer were identified, and 41.2% underwent operative intervention. Approximately 46% of nonoperatively managed patients lacked a contraindication. Operatively managed patients had longer overall survival (OS) than those who were nonoperatively managed or untreated (25.1 months vs. 11.1 months vs. 5.1 months, p

BackgroundSymptom status is an important indicator of disease progression in patients with heart failure (HF). Perceived control is a target of most self-care interventions and is associated with better outcomes in HF; however, little is known about the relationship between perceived control and symptom status in patients with HF.ObjectiveThe aims of this study were to (1) determine the relationship of perceived control to HF symptom status and (2) examine the associations of perceived control to self-care and of self-care to symptom status.MethodsA total of 115 patients with HF were included. Data on symptom status (Memorial Symptom Assessment Scale-HF), perceived control (Control Attitudes Scale-Revised), and self-care (Self-Care of Heart Failure Index) were collected. Other covariates included were age, gender, New York Heart Association class, comorbidity burden, and depressive symptoms. Multiple regression analyses were performed to analyze the data.ResultsLower perceived control predicted worse symptom status after controlling for covariates (P = .009). Other covariates predictive of worse symptom status were younger age, New York Heart Association class III/IV, and higher levels of depressive symptoms. Higher levels of perceived control were associated with better self-care (P = .044). Better self-care was associated with better symptom status (P = .038).ConclusionsLower levels of perceived control were independently associated with worse symptom status in patients with HF. Intervention strategies targeting perceived control should be tested to determine whether they could improve symptom status.

Depressive symptoms are substantial among stroke survivors and their caregivers in poststroke management. Optimism and social support are known to protect against depressive symptoms. However, little is known about how optimism and social support contribute to depressive symptoms among stroke survivor-caregiver dyads. The study's purpose was to examine actor and partner effects of optimism on depressive symptoms through perceived social support among stroke survivors and caregiver dyads in the chronic stage of rehabilitation.Stroke survivors and caregivers (N = 105 dyads) completed the survey at 2 years of follow-up after the first stroke. Depressive symptoms, optimism, and perceived social support were assessed using the Center for Epidemiologic Studies-Depression, the Life Orientation Test, and the Interpersonal Support Evaluation List. The Actor-Partner Interdependence Model Extended to Mediation analysis was used to test the indirect effect of optimism on depressive symptoms through perceived social support.Higher optimism was significantly associated with lower depressive symptoms for caregivers (direct actor effect, -0.6844; 95% confidence interval [CI], -0.9844 to -0.3844) and stroke survivors (direct partner effect, -0.4189; 95% CI, -0.0789 to -0.0889). Perceived social support availability significantly mediated the association between optimism and depressive symptoms for stroke survivors (indirect effect, -0.1957; 95% CI, -0.3923 to -0.0670). Caregiver perceived social support availability was also a significant mediator between caregivers' optimism and stroke survivors' depressive symptoms (indirect effect, 0.1658; 95% CI, 0.0559-0.3128).Intervention improving dyad members' optimism and social support would be beneficial to improve depressive symptoms of the stroke survivors and caregivers in chronic stroke management.

International audience; Prader-Willi syndrome (PWS) is a rare neuroendocrine genetic syndrome. Characteristics of PWS include hyperphagia, hypotonia, and intellectual disability. Pituitary hormone deficiencies, caused by hypothalamic dysfunction, are common and hypogonadism is the most prevalent. Untreated hypogonadism can cause osteoporosis, which is already an important issue in PWS. Therefore, timely detection and treatment of hypogonadism is crucial. To increase understanding and prevent undertreatment, we (1) performed a cohort study in the Dutch PWS population, (2) thoroughly reviewed the literature on female hypogonadism in PWS and (3) provide clinical recommendations on behalf of an international expert panel. For the cohort study, we retrospectively collected results of a systematic health screening in 64 female adults with PWS, which included a medical questionnaire, medical file search, medical interview, physical examination and biochemical measurements. Our data show that hypogonadism is frequent in females with PWS (94%), but is often undiagnosed and untreated. This could be related to unfamiliarity with the syndrome, fear of behavioral changes, hygienic concerns, or drug interactions. To prevent underdiagnosis and undertreatment, we provide practical recommendations for the screening and treatment of hypogonadism in females with PWS.

Background: Rural family caregivers experience high levels of stress, burden, and psychological distress related to caregiving and are at higher risk for cardiovascular disease (CVD) compared to non-caregivers. Health activation (known also as patient activation) is an indicator of engagement in self-care and is defined as an individual’s knowledge, skill, and confidence in managing health. Better health activation is associated with better health outcomes. Because rural individuals are at greater risk of CVD and have fewer supportive resources than those in urban environments, we wanted to determine the relationship of health activation with risk for future CVD in this population. Objective: The purpose of this study was to examine the association of health activation with risk for future CVD among rural family caregivers of patients with chronic illness. Methods: This was a cross-sectional study using baseline data from a randomized controlled trial of an intervention to reduce CVD risk for rural caregivers. We measured health activation using the Patient Activation Measure. The predicted10-year risk of CVD was assessed using the Framingham risk score. Covariates potentially related to cardiovascular risks among caregivers were collected including stress (Perceived Stress Scale-Cohen), anxiety (Brief Symptom Inventory), depressive symptoms (Patient Health Questionnaire-9), and caregiver burden (Zarit Burden Interview). Generalized linear regression was used to analyze data. Results: Of 217 caregivers (mean age 53 ± 13 years, 79% female), 48% were caring for a spouse, 20% were caring for a parent, and the remaining 32% were caring for a sibling, a child, or other relatives. Caregivers with higher health activation had a lower risk of developing CVD in the future based on their Framingham risk score (B = -0.081, SE= 0.039, 95% CI= -0.158 to -0.004, p=0.038), independent of the other covariates. Every 10-point increase in health activation score was associated with a nearly 1-point (0.81) decrease in Framingham risk score. Conclusions: Health activation is a good predictor of future risk for developing CVD. Development and testing of interventions to promote health activation before people develop CVD is suggested to decrease the risk of future CVD.

Prader-Willi syndrome (PWS) is a complex genetic syndrome characterized by hyperphagia, intellectual disability, hypotonia and hypothalamic dysfunction. Adults with PWS often have hormone deficiencies, hypogonadism being the most common. Untreated male hypogonadism can aggravate PWS-related health issues including muscle weakness, obesity, osteoporosis, and fatigue. Therefore, timely diagnosis and treatment of male hypogonadism is important. In this article, we share our experience with hypogonadism and its treatment in adult males with PWS and present a review of the literature. In order to report the prevalence and type of hypogonadism, treatment regimen and behavioral issues, we retrospectively collected data on medical interviews, physical examinations, biochemical measurements and testosterone replacement therapy (TRT) in 57 Dutch men with PWS. Fifty-six (98%) of the patients had either primary, central or combined hypogonadism. Untreated hypogonadism was associated with higher body mass index and lower hemoglobin concentrations. TRT was complicated by behavioral challenges in one third of the patients. Undertreatment was common and normal serum testosterone levels were achieved in only 30% of the patients. Based on the Dutch cohort data, review of the literature and an international expert panel discussion, we provide a practical algorithm for TRT in adult males with PWS in order to prevent undertreatment and related adverse health outcomes.

Background The management of flat epithelial atypia (FEA) on core needle biopsy remains controversial. The upstaging rates after surgical excision are variable. In this study, we seek to determine the upstaging rate of FEA at our institution. Methods Patients with a diagnosis of FEA were identified from the institution’s pathology database from 2009 to 2018. Patients were included in the study if FEA alone, without atypia or cancer, was identified on core needle biopsy. Patient demographics, imaging, management, and pathology characteristics were obtained. Statistical analysis performed using IBM SPSS 26.0 (Armonk, NY, USA). Results FEA was diagnosed on core needle biopsy in 235 patients from 2009 to December 2018. Forty-eight patients met the inclusion criteria. The majority of patients presented with calcifications on mammogram (n = 21, 64%) with the remainder as masses (n = 6, 18%) or architectural distortion (n = 6, 18%). Of those, 15 (31%) patients declined surgical excision, of which none developed cancer over a mean follow-up of 4.4 years. Of the 33 (69%) patients undergoing excisional biopsy, 17 (52%) confirmed FEA, 11 (33%) had benign findings, and 3 (9%) demonstrated atypical ductal hyperplasia on final pathology. One (3%) case revealed ductal carcinoma in situ (DCIS) and 1 (3%) was upgraded to invasive cancer for an overall upstaging rate of 4% (2/48). After a mean follow-up of 3.4 years, none of the excisional biopsy patients developed invasive breast cancer. Adjuvant therapy was used in the cases of DCIS and invasive cancer; however, chemoprevention with raloxifene or tamoxifen was not chosen by any of the remaining patients. Conclusion In our cohort, expectant management of FEA alone appears to be a safe option as our upstaging rate to DCIS or invasive cancer for FEA diagnosed on core biopsy was only 4%. Our study suggests that close follow-up is a safe and feasible option for pure FEA without a radiographic discordance found on core biopsy.

Background:Prader-Willi Syndrome (PWS) is a neurodevelopmental genomic imprinting disorder with lack of expression of genes inherited from the paternal chromosome 15q11-q13 region usually from paternal 15q11-q13 deletions (about 60%) or maternal uniparental disomy 15 or both 15s from the mother (about 35%). An imprinting center controls the expression of imprinted genes in the chromosome 15q11-q13 region. Key findings include infantile hypotonia, a poor suck, failure to thrive and hypogonadism/hypogenitalism. Short stature and small hands/feet due to growth and other hormone deficiencies, hyperphagia and marked obesity occur in early childhood, if uncontrolled. Cognitive and behavioral problems (tantrums, compulsions, compulsive skin picking) are common.Objective:Hyperphagia and obesity with related complications are major causes of morbidity and mortality in PWS. This report will describe an accurate diagnosis with determination of specific genetic subtypes, appropriate medical management and best practice treatment approaches.Methods and Results:An extensive literature review was undertaken related to genetics, clinical findings and laboratory testing, clinical and behavioral assessments and summary of updated health-related information addressing the importance of early PWS diagnosis and treatment. A searchable, bulleted and formatted list of topics is provided utilizing a Table of Contents approach for the clinical practitioner.Conclusions:Physicians and other health care providers can use this review with clinical, genetic and treatment summaries divided into sections pertinent in the context of clinical practice. Frequently asked questions by clinicians, families and other interested participants or providers will be addressed.

Background Although the implantable cardioverter defibrillator (ICD) has a survival benefit for the prevention of sudden cardiac death, ICD recipients commonly experience emotional distress as a consequence of ICD shocks. Objective The aim of this study was to examine whether the association between ICD shocks and psychological distress (anxiety and depressive symptoms) is mediated by ICD-related concerns and perceived control among ICD recipients. Methods This was a multinational cross-sectional observational study of 334 ICD recipients. Patients reported the number of shocks received since ICD implantation and completed questionnaires to assess anxiety, depressive symptoms, ICD-related concerns, and perceived control. A path analysis was conducted to explore the relationship of receiving ICD shocks with anxiety and depressive symptoms and the mediating effects of ICD-related concerns and perceived control. Results Of the 334 ICD recipients, 39.2% experienced ICD shocks at least once since implantation. There was no direct effect of ICD shocks on anxiety and depressive symptoms. Experiencing ICD shocks was indirectly associated with an increased likelihood of anxiety and depressive symptoms via the pathways of ICD-related concerns and perceived control (indirect effects on anxiety = 0.060, 0.043; indirect effect on depressive symptoms = 0.025, 0.073). Conclusion Experiencing defibrillator shocks was associated with psychological distress in ICD recipients; the relationship was fully mediated by ICD-related concerns and perceived control. These results suggest that clinicians should routinely assess ICD-related concerns and perceived control in patients with ICD. Research is needed to develop and test interventions to decrease emotional distress related to the ICD shock experience.

Prader‐Willi syndrome (PWS) is generally due to sporadic paternal deletions of the chromosome 15q11‐q13 region followed by maternal disomy 15. Advanced maternal age is more commonly seen in those with maternal disomy 15. Environmental factors (e.g., drug use, occupational chemical exposure, infectious agents, and irradiation) could account for chromosome changes. Previous evidence of differences in male and female gametogenesis could suggest an environmental role in the causation of the paternal 15q11‐q13 deletion seen in PWS. Certain occupations such as hydrocarbon‐exposing occupations (e.g., landscaping, farming, and painting) and viral exposure (e.g., human coronavirus 229E causing upper respiratory infections in adults with an incorporation site in the human genome at chromosome 15q11) can be seasonal in nature and contribute to chromosome damage. To assess, we reviewed birth seasonality data in a large cohort of individuals with PWS recruited nationally (N = 355) but no significant differences were seen by month between those with the 15q11‐q13 deletion compared with maternal disomy 15 when analyzing quarterly seasonal patterns. Although early evidence supported birth seasonality differences in PWS, a larger number of individuals in our recent study using advanced genetic testing methods did not find this observation.

Background The prevalence of multi-morbidity in implantable cardioverter defibrillator (ICD) recipients is approximately 25%. Multi-morbidity is associated with poor health and psychological outcomes in this population and may affect ICD recipients' quality-of-life (QOL). The purpose of this study was to determine the prevalence of psychological distress (anxiety, depressive symptoms, and Type-D personality) in ICD recipients with varying levels of comorbidities, and to examine the association between multi-morbidity burden and QOL in this population. Methods All adults listed in the Swedish ICD and Pacemaker Registry in 2012 with an ICD implanted for at least one year were invited to participate in this study. Binary logistic regression was used to predict QOL using the EQ-5D mean index dichotomized based on median QOL scores. Multi-morbidity burden scores were based on quartile groupings. Results A total of 2658 ICD recipients participated in the study (with a mean age of 65, 20.6% female, mean implant duration of 4.7 years, with 35.4% implanted for primary prevention of sudden cardiac arrest). Greater multi-morbidity burden, female sex, not working outside the home, history of ICD shock, negative ICD experience, higher levels of ICD-related concerns, and the presence of anxiety, depression, or Type D personality were associated with worse QOL in ICD recipients. Predictors differed by multi-morbidity burden level. Conclusions Multi-morbidity burden and psychological distress is an essential factor related to QOL. This issue should be discussed with potential ICD recipients prior to implant. Further exploration of increased recognition and treatment of psychological distress in ICD recipients is warranted.

Platelets are activated in solid cancers, including pancreatic ductal adenocarcinoma (PDA), a highly aggressive malignancy with a devastating prognosis and limited therapeutic options. The mechanisms by which activated platelets regulate tumor progression are poorly understood. The nucleotide-binding domain leucine-rich repeat containing protein 3 (NLRP3) inflammasome is a key inflammatory mechanism recently identified in platelets, which controls platelet activation and aggregation. In an orthotopic PDA mouse model involving surgical implantation of Panc02 murine cancer cells into the tail of the pancreas, we show that the NLRP3 inflammasome in circulating platelets is upregulated in pancreatic cancer. Pharmacological inhibition or genetic ablation of NLRP3 in platelets resulted in decreased platelet activation, platelet aggregation, and tumor progression. Moreover, interfering with platelet NLRP3 signaling significantly improved survival of tumor-bearing mice. Hence, the platelet NLRP3 inflammasome plays a critical role in PDA and might represent a novel therapeutic target.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): In Australia, this study received funding from a faculty grand by Australian University Faculty of Health Sciences Research grant. In the United States, the study was funded by a research professor award from University of Kentucky. Background. Shared decision-making is important for ICD recipients to fully contemplate and rationally decide about ICD deactivation at end-of-life. Although discussions about device deactivation at end-of-life are recommended to be held before ICD implantation and throughout the illness trajectory, such discussions rarely occur in clinical practice. Purpose. To identify whether ICD recipients’ experiences of end-of-life discussions with clinicians are associated with openness to discussing ICD deactivation at end-of-life. Methods. This cross-sectional study included 293 ICD recipients living in the United States, Australia, and South Korea (mean age 59, 22.5% female, mean ICD implantation 10 years). Hierarchical logistic regression was used to determine whether patients’ experiences of shared decision-making were associated with openness to discuss device deactivation at end-of-life after controlling for relevant covariates (i.e. age, gender, ICD implantation years, ICD shock experience, general ICD experience, ICD knowledge, and concerns related to the ICD). Results. About half of the participants (57.7%) were open to discussing ICD deactivation at end-of-life with clinicians. Almost one-quarter (23.5%) had no prior experience of discussing any end-of-life issues with clinicians. Patients’ past experiences of end-of-life discussions with clinicians were significantly associated with openness to discuss device deactivation at end-of-life (OR: 1.30) after adjusting for covariates. Conclusion. Our results highlight that clinicians’ willingness to discuss sensitive end-of-life issues such as battery replacement and deactivation of defibrillation therapy empowers patients to actively engage in end-of-life discussions.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): National Institutes of Health (NIH) Background The poor taste foods in a low sodium diet and patients’ preferences for salty foods are known barriers to sodium restricted diet (SRD) adherence. Older adults may experience less enjoyment of SRD due to decreased sense of taste. However, little is known about how age is associated with sodium intake, preference for salt, and enjoyment of SRD in patients with heart failure (HF). Purpose The purpose of this study was to examine effect of age on dietary sodium intake through their preference for salt and enjoyment of SRD in patients with HF. Methods In this cross-sectional study, we used baseline data from participants in a randomized controlled trial of a SRD intervention for patients with HF and their caregivers. Patients were asked to collect 24-hour urine to measure dietary sodium intake. Preference for salty food and enjoyment of SRD were assessed using a question on an 11-point numeric scale (range 0 to 10). Parallel mediation analyses were conducted using the PROCESS macro program in SPSS with 5,000 bootstrap samples. Results A total of 136 patients with HF (64% male, mean age = 60.3 ± 14.4, range 27 to 90, 80.1% white) had a mean 24-hr urine sodium of 4320mg (SD = 2053, range: 1553 mg – 11495 mg) with most (71%) having a 24-hr urine sodium > 3000mg. The mean preference for salty food was 5.3 (SD = 2.8) on a scale from 0 to 10 with 10 indicating greater preference and enjoyment of SRD was 4.4 (SD = 2.5) on the same scale. Age was significantly associated with sodium intake in that older patients were more likely to eat less sodium (effect= -40.3236, 95% CI= [-63.7151, -16.9321]). The indirect effects of age on sodium intake through preference of salty food (effect= .7033, 95% CI = [-2.3361, 4.5357]) and enjoyment of SRD (effect = -.0271, 95% CI = [ -3.2736, 2.2213]) were not significant, indicating that these factors did not mediate the relationship between age and dietary sodium consumption. When we controlled gender, education, and ethnicity, age was also associated with sodium intake, but the two indirect effects were not significant. Conclusion Although most patients consumed foods high in sodium, older patients were more likely to consume foods lower in salt. However, contrary to what we expected, preference for salty foods and enjoyment of SRD did not play mediator roles in the association of age with salt consumption. The findings suggest that older adults may need different types of intervention to promote adherence than younger patients. Further research is needed to explore other factors related to SRD (e.g., efficacy of SRD or perceived control of diet behaviors) that affect sodium intake in patients with HF.