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Colonic self-expanding metal stents (SEMS) can be used to relieve malignant and benign large bowel obstruction (LBO) as a bridge to surgery (BTS) and for palliation. Guidelines suggest the use of fluoroscopic guidance for deployment. This may be difficult to obtain after hours and in certain centers. We aimed to determine the outcomes of stenting under endoscopic guidance alone.All patients who underwent SEMS insertion in our tertiary referral center between August 2010 and June 2021 were identified from a prospectively maintained database. Patient demographics (age/gender), disease characteristics (benign versus malignant/location/stage), stenting intent (BTS versus palliative), and outcomes (technical success/stoma/time from stenting to resection/death/study end) were analyzed.Fifty-three (n = 39, 73.6% male) patients underwent SEMS insertion. Indications included colorectal carcinoma (n = 48, 90.6%), diverticular stricture (n = 3), and gynecological malignancy (n = 2). In five (9.4%) patients (four BTS and one palliative), SEMSs deployment was not completed because of the inability to pass the guidewire. All underwent emergency surgery. In the BTS cohort (n = 29, median 70.4 [range 40.3-91.8] years), 10 patients underwent neoadjuvant chemoradiotherapy. The permanent stoma rate was 20.7% (n = 6). There was no 30- or 90-d mortality. In the palliative cohort (n = 24, median age 77.1 [range 54.4-91.9]), 16 (66.7%) were deceased at the study end. The median time from stenting to death was 5.2 (2.3-7.9) months.SEMS placed under endoscopic visualization alone, palliatively and as a BTS, had acceptable stoma, morbidity, and mortality rates. These results show that SEMS insertion can be safely performed without fluoroscopy.

The increasing cost of cosmetic procedures, long elective waiting times in the public system and affordability of procedures offered abroad has driven the rapid growth of cosmetic tourism. The incidence and cost of patients presenting to the Irish health service with complications related to cosmetic procedures carried out in overseas institutions is largely unknown. This heterogenous group of patients is challenging to identify. Limited data exists for this patient group in the Irish context. We aimed to perform a multicentre audit and cost analysis of patients presenting to Irish health services with complications related to cosmetic procedures performed in overseas institutions over a 2 year period.Patients presenting to two University Hospitals from March 2019-April 2021 with complications after a cosmetic surgical procedure was performed abroad were studied. The HPO ABF 2020 price list data was used to calculate the inpatient and procedure cost for each subject.14 (13/92.8% female, mean age 43 ± 11.85 years) patients presented during the study period. Countries of cosmetic operation included: Belgium (6/46.2%), the UK (2/15.4%), Latvia, Turkey, Poland, Lithuania, and Estonia (1 patient/7.7% each country). All required a re-operative procedure. These interventions included: removal of infected implant (n = 1), adjustment or removal of a gastric band (n = 9) and debridement of an infected/necrotic wound (n = 3). Mean length of stay was 9.14 ± 7.48 (range 2-28) days. Five (38.4%) patients required vac dressing. The mean cost of the cohort for the interventional procedure and in-patient stay was €15912.53 (+/- €6388). The sum total of all the costs for the cohort was €231038.60.Significant costs were associated with prolonged hospital admissions, operative interventions, intravenous antibiotics, VAC dressing application and follow up visits. Complications from procedures performed in overseas institutions account for a significant cost burden to health services in Ireland.

This systematic review addresses the central research question, “what is known from the published, peer-reviewed literature about the impact of diabetes on the risk of bacterial urinary tract infections (UTI)?” We examine the results from laboratory studies where researchers have successfully adapted mouse models of diabetes to study the pathophysiology of ascending UTI. These studies have identified molecular and cellular effectors shaping immune defenses against infection of the diabetic urinary tract. In addition, we present evidence from clinical studies that in addition to diabetes, female gender, increased age, and diabetes-associated hyperglycemia, glycosuria, and immune impairment are important risk factors which further increase the risk of UTI in diabetic individuals. Clinical studies also show that the uropathogenic genera causing UTI are largely similar between diabetic and nondiabetic individuals, although diabetes significantly increases risk of UTI by drug-resistant uropathogenic bacteria.

The vast majority of adolescents and young adults are active on Social Networking Sites (SNSs). SNSs are influential, risk-conducive environments for alcohol use among adolescents and young adults. Specifically, posting or sharing alcohol-related content (ARC) is associated with higher levels of alcohol use. However, it is unknown if sharing different types of ARC associates differentially with alcohol use and consequences. The goal of the current project was to develop a measure of the likelihood of posting key types of ARC posted by adolescents and young adults and to examine their associations with SNS use patterns and actual alcohol-related behavior. Participants were 15 to 20 years of age (n=306; 46.7% male; 56.6% Caucasian/White; 27.0% Asian) who completed a battery of self-report measures. Results from an Exploratory Factor Analysis revealed four types of ARC: (1) Self and Friend Consumption, (2) Memes and Viral Photos, (3) Status Updates: Others’ Drinking and Consequences, and (4) Pictures: Others’ Drinking and Consequences. Participants’ likelihood of posting Self and Friend Consumption was significantly associated with heightened Snapchat use, typical drinks per week, peak drinking, and negative drinking consequences. Whereas youth appear to share more readily alcohol-related viral posts and memes, it seems that the sharing of ARC that is specifically related to the participants’ own use or friends’ use is salient concerning alcohol use and problems. Therefore, interventions might consider sending targeted prevention messages to individuals who share certain types of ARC which are more associated with problematic alcohol behaviors.

PURPOSE Eight percent of young-adult childhood cancer survivors meet criteria for frailty, an aging phenotype associated with poor health. In the elderly general population, frailty is associated with neurocognitive decline; this association has not been examined in adult survivors of childhood cancer. METHODS Childhood cancer survivors 18-45 years old (≥ 10 years from diagnosis) were clinically evaluated for prefrailty or frailty (respectively defined as ≥ 2 or ≥ 3 of: muscle wasting, muscle weakness, low energy expenditure, slow walking speed, and exhaustion [Fried criteria]) and completed neuropsychologic assessments at enrollment (January 2008-June 2013) and 5 years later. Weighted linear regression using inverse of sampling probability estimates as weights compared differences in neurocognitive decline in prefrail and frail survivors versus nonfrail survivors, adjusting for diagnosis age, sex, race, CNS–directed therapy (cranial radiation, intrathecal chemotherapy, and neurosurgery), and baseline neurocognitive performance. RESULTS Survivors were on average 30 years old and 22 years from diagnosis; 18% were prefrail and 6% frail at enrollment. Frail survivors declined an average of 0.54 standard deviation (95% CI, −0.93 to −0.15) in short-term verbal recall, whereas nonfrail survivors did not decline (β = .22; difference of βs = −.76; 95% CI, −1.19 to −0.33). Frail survivors declined more than nonfrail survivors on visual-motor processing speed (β = −.40; 95% CI, −0.67 to −0.12), cognitive flexibility (β = −.62; 95% CI, −1.02 to −0.22), and verbal fluency (β = −.23; 95% CI, −0.41 to −0.05). Prefrail and frail survivors experienced greater declines in focused attention (prefrail β = −.35; 95% CI, −0.53 to −0.17; frail β = −.48; 95% CI, −0.83 to −0.12) compared with nonfrail survivors. CONCLUSION Over approximately 5 years, prefrail and frail young-adult survivors had greater declines in cognitive domains associated with aging and dementia compared with nonfrail survivors. Interventions that have global impact, designed to target the mechanistic underpinnings of frailty, may also mitigate or prevent neurocognitive decline.

PURPOSE Cervical cancer is the leading cause of cancer death for women in Botswana. Barriers in access to cancer care can lead to later stages at diagnosis and increased mortality. This study evaluated access, defined as travel time from a patient's residential village to a multidisciplinary team clinic in Gaborone, with stage of cervical cancer at presentation. In addition, because of the high HIV prevalence in Botswana, we explored the association between travel time and HIV status. METHODS Eligible patients with cervical cancer presenting to the multidisciplinary team between 2015 and 2020 were included. Data were abstracted from questionnaires and hospital records. Google Maps was used to calculate travel time. Multinomial regression was used to examine travel time and cancer stage, and multivariable logistic regression was used to investigate travel time and HIV status. RESULTS We identified 959 patients with cervical cancer of which 70.1% were women living with HIV. The median travel time was approximately 2 hours. Using a reference group of stage I disease and a travel time of < 1 hour, the odds of presenting with stage II increased for patients traveling 3-5 hours (adjusted odds ratio [OR], 2.00; 95% CI, 1.14 to 3.52) and > 5 hours (OR, 2.19; 95% CI, 1.15 to 4.19). There were no significant associations for stage III. For stage IV disease, the odds were increased for patients traveling 3-5 hours (OR, 2.93; 95% CI, 1.26 to 6.79) and > 5 hours (adjusted OR, 4.05; 95% CI, 1.62 to 10.10). In addition, the odds of patients presenting living with HIV increased with increasing travel time (trend test = 0.004). CONCLUSION This study identified two potential factors, travel time and HIV status, that influence access to comprehensive cervical cancer care in Botswana.

BACKGROUND: The objective of this study was to determine the impact of seizure-related factors on neurocognitive, health-related quality of life (HRQOL), and social outcomes in survivors of childhood cancer. METHODS: Survivors of childhood cancer treated at St. Jude Children’s Hospital (n = 2022; 48.3% female; median age, 31.5 years; median time since diagnosis, 23.6 years) completed neurocognitive testing and questionnaires. The presence, severity, resolution, and treatment history of seizures were abstracted from medical records. Adjusting for the age at diagnosis, sex, and prior cancer therapy, multivariable models examined the impact of seizures on neurocognitive and HRQOL outcomes. Mediation analyses were conducted for social outcomes. RESULTS: Seizures were identified in 232 survivors (11.5%; 29.9% of survivors with central nervous system [CNS] tumors and 9.0% of those without CNS tumors). In CNS tumor survivors, seizures were associated with poorer executive function and processing speed (P < .02); in non-CNS tumor survivors, seizures were associated with worse function in every domain (P < .05). Among non-CNS survivors, seizure severity was associated with worse processing speed (P = .023), and resolution was associated with better executive function (P = .028) and attention (P = .044). In CNS survivors, seizure resolution was associated with improved attention (P = .047) and memory (P < .02). Mediation analysis revealed that the impact of seizures on social outcomes was mediated by neurocognitive function. CONCLUSIONS: Seizures in cancer survivors adversely affect long-term functional and psychosocial outcomes independently of cancer therapy. The resolution of seizure occurrence is associated with better outcomes. Seizure severity is associated with poorer outcomes and should be a focus of clinical management and patient education.

Background Breast cancer is a heterogeneous disease, divided into subtypes based on the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Subtypes have different biology and prognosis, with accumulating evidence of different risk factors. The purpose of this study was to compare breast cancer risk factors across tumor subtypes in a large, diverse mammography population. Methods Women aged 40–84 without a history of breast cancer with a screening mammogram at three United States health systems from 2006 to 2015 were included. Risk factor questionnaires were completed at mammogram visit, supplemented by electronic health records. Invasive tumor subtype was defined by immunohistochemistry as ER/PR+HER2−, ER/PR+HER2+, ER, and PR−HER2+, or triple‐negative breast cancer (TNBC). Cox proportional hazards models were run for each subtype. Associations of race, reproductive history, prior breast problems, family history, breast density, and body mass index (BMI) were assessed. The association of tumor subtypes with screen detection and interval cancer was assessed using logistic regression among invasive cases. Results The study population included 198,278 women with a median of 6.5 years of follow‐up (IQR 4.2–9.0 years). There were 4002 invasive cancers, including 3077 (77%) ER/PR+HER2−, 300 (8%) TNBC, 342 (9%) ER/PR+HER2+, and 126 (3%) ER/PR−HER2+ subtype. In multivariate models, Black women had 2.7 times higher risk of TNBC than white women (HR = 2.67, 95% CI 1.99–3.58). Breast density was associated with increased risk of all subtypes. BMI was more strongly associated with ER/PR+HER2− and HER2+ subtypes among postmenopausal women than premenopausal women. Breast density was more strongly associated with ER/PR+HER2− and TNBC among premenopausal than postmenopausal women. TNBC was more likely to be interval cancer than other subtypes. Conclusions These results have implications for risk assessment and understanding of the etiology of breast cancer subtypes. More research is needed to determine what factors explain the higher risk of TNBC for Black women., Breast cancer is a heterogeneous disease, with subtypes that may have different etiologies. This study evaluated traditional breast cancer risk factors across tumor subtypes, finding distinct sets of risk factors for each subtype. We additionally discuss implications for screening and risk assessment.

Background: Total pancreatectomy has high morbidity and mortality and differences among countries are currently unknown. This study compared the use and postoperative outcomes of total pancreatec-tomy among 4 Western countries. Methods: Patients who underwent one-stage total pancreatectomy were included from registries in the United States, Germany, the Netherlands, and Sweden (2014-2018). Use of total pancreatectomy was assessed by calculating the ratio total pancreatectomy to pancreatoduodenectomy. Primary outcomes were major morbidity (Clavien Dindo >3) and in-hospital mortality. Predictors for the primary outcomes were assessed in multivariable logistic regression analyses. Sensitivity analysis assessed the impact of volume (low-volume 40 pancreatoduodenectomies annually; data available for the Netherlands and Germany). Results: In total, 1,579 patients underwent one-stage total pancreatectomy. The relative use of total pancreatectomy to pancreatoduodenectomy varied up to fivefold (United States 0.03, Germany 0.15, the Netherlands 0.03, and Sweden 0.15; P < .001). Both the indication and several baseline characteristics differed significantly among countries. Major morbidity occurred in 423 patients (26.8%) and differed (22.3%, 34.9%, 38.3%, and 15.9%, respectively; P < .001). In-hospital mortality occurred in 85 patients (5.4%) and also differed (1.8%, 10.2%, 10.8%, 1.9%, respectively; P < .001). Country, age >75, and vascular resection were predictors for in-hospital mortality. In-hospital mortality was lower in high-volume centers in the Netherlands (4.9% vs 23.1%; P = .002), but not in Germany (9.8% vs 10.6%; P = .733). Conclusion: Considerable differences in the use of total pancreatectomy, patient characteristics, and postoperative outcome were noted among 4 Western countries with better outcomes in the United States and Sweden. These large, yet unexplained, differences require further research to ultimately improve patient outcome. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Lung cancers harboring mesenchymal-to-epithelial transition factor (MET) genetic alterations, such as exon 14 skipping mutations or high-level gene amplification, respond well to MET-selective tyrosine kinase inhibitors (TKI). However, these agents benefit a relatively small group of patients (4%–5% of lung cancers), and acquired resistance limits response durability. An antibody–drug conjugate (ADC) targeting MET might enable effective treatment of MET-overexpressing tumors (approximately 25% of lung cancers) that do not respond to MET targeted therapies. Using a protease-cleavable linker, we conjugated a biparatopic METxMET antibody to a maytansinoid payload to generate a MET ADC (METxMET-M114). METxMET-M114 promotes substantial and durable tumor regression in xenografts with moderate to high MET expression, including models that exhibit innate or acquired resistance to MET blockers. Positron emission tomography (PET) studies show that tumor uptake of radiolabeled METxMET antibody correlates with MET expression levels and METxMET-M114 efficacy. In a cynomolgus monkey toxicology study, METxMET-M114 was well tolerated at a dose that provides circulating drug concentrations that are sufficient for maximal antitumor activity in mouse models. Our findings suggest that METxMET-M114, which takes advantage of the unique trafficking properties of our METxMET antibody, is a promising candidate for the treatment of MET-overexpressing tumors, with the potential to address some of the limitations faced by the MET function blockers currently in clinical use.

Background Centralization of pancreatic surgery in the Netherlands has been ongoing since 2011. The aim of this study was to assess how centralization has affected the likelihood of resection and survival of patients with non-metastatic pancreatic head and periampullary cancer, diagnosed in hospitals with and without pancreatic surgery services. Methods An observational cohort study was performed on nationwide data from the Netherlands Cancer Registry (2009–2017), including patients diagnosed with non-metastatic pancreatic head or periampullary cancer. The period of diagnosis was divided into three time intervals: 2009–2011, 2012–2014 and 2015–2017. Hospital of diagnosis was classified as a pancreatic or non-pancreatic surgery centre. Analyses were performed using multivariable logistic and Cox regression models. Results In total, 10 079 patients were included, of whom 3114 (30.9 per cent) were diagnosed in pancreatic surgery centres. Between 2009–2011 and 2015–2017, the number of patients undergoing resection increased from 1267 of 3169 (40.0 per cent) to 1705 of 3566 (47.8 per cent) (P for trend Conclusion After centralization of pancreatic surgery, the resection rate for patients with pancreatic head and periampullary cancer diagnosed in non-pancreatic surgery centres increased and became similar to that in pancreatic surgery centres. Overall survival remained higher in patients diagnosed in pancreatic surgery centres.

Background and ObjectivesTo examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern–specific ways.MethodsMR neuroimaging and NIH Stroke Scale data at index stroke and the modified Rankin Scale (mRS) score at 3–6 months after stroke were obtained from the MRI–Genetics Interface Exploration study of patients with acute ischemic stroke (AIS). Individual WMH volume was automatically derived from fluid-attenuated inversion recovery images. Stroke lesions were automatically segmented from diffusion-weighted imaging (DWI) images, parcellated into atlas-defined brain regions and further condensed to 10 lesion patterns via machine learning–based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS score >2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age2, sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts.ResultsA total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location–specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location.DiscussionHigher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions.

Laparoscopic surgery for complicated Crohn's (CD) is often technically challenging. Previous studies are limited by the comparison of heterogeneous cohorts of patients undergoing laparoscopic vs open surgery. We aimed to compare perioperative and long-term outcomes of matched patients undergoing laparoscopic and open colonic and ileocolonic resection. Primary outcomes were operative time, blood loss, and complications. Long-term outcomes were subsequent intraabdominal CD surgery, incisional hernia repair, and stoma reversal rates.Laparoscopic and open CD patients were 1:1 propensity score matched on age, body mass index, sex, indication, ASA grade, prior abdominal surgery, and postoperative Crohn's medication use based on the laparoscopic approach.A total of 906 patients underwent surgery for complex CD. After propensity matching, 386 were analyzed (193 open/193 lap, 51.3% male, mean age 33.9 + / - 12.6). Mean follow-up was 9.8 (range 7.9-12.1) years. Length of stay [(LOS) 6 (4, 8) vs 8 (5, 11) days, p 0.001] and operative time [154 (110, 216) vs 176 (126, 239) min, p = 0.03] were shorter in the laparoscopic group. There was no difference in other complications or mortality. After adjusting for postoperative medications, no association was found between operative approach and subsequent intra-abdominal operation or incisional hernia repair. Laparoscopic patients were less likely to have postoperative sepsis [OR 0.40 (0.18, 0.91), p = 0.03].In the setting of complicated Crohn's, in matched cohorts, laparoscopic surgery is associated with reduced operative times and LOS. Mortality, reoperation, and symptomatic hernia rates were equivalent to open surgery. Patients undergoing laparoscopic surgery are less likely to experience postoperative sepsis.

OBJECTIVE: This analysis aimed to compare failure to rescue (FTR) after pancreatoduodenectomy across the Atlantic. SUMMARY BACKGROUND DATA: FTR, or mortality after development of a major complication, is a quality metric originally created to compare hospital results. FTR has been studied in North American and Northern European patients undergoing pancreatoduodenectomy (PD). However, a direct comparison of FTR after PD between North America and Northern Europe has not been performed. METHODS: Patients who underwent PD in North America, the Netherlands, Sweden and Germany (GAPASURG dataset) were identified from their respective registries (2014-17). Patients who developed a major complication defined as Clavien-Dindo ≥3 or developed a grade B/C postoperative pancreatic fistula (POPF) were included. Preoperative, intraoperative, and postoperative variables were compared between patients with and without FTR. Variables significant on univariable analysis were entered into a logistic regression for FTR. RESULTS: Major complications occurred in 6188 of 22,983 patients (26.9%) after PD, and 504 (8.1%) patients had FTR. North American and Northern European patients with complications differed, and rates of FTR were lower in North America (5.4% vs 12%, P < 0.001). Fourteen factors from univariable analysis contributing to differences in patients who developed FTR were included in a logistic regression. On multivariable analysis, factors independently associated with FTR were age, American Society of Anesthesiology ≥3, Northern Europe, POPF, organ failure, life-threatening complication, nonradiologic intervention, and reoperation. CONCLUSIONS: Older patients with severe systemic diseases are more difficult to rescue. Failure to rescue is more common in Northern Europe than North America. In stable patients, management of complications by interventional radiology is preferred over reoperation.

Neuropsychiatric lupus (NPSLE), a manifestation of the autoimmune disease systemic lupus erythematosus (SLE), is characterized by psychiatric symptoms including anxiety and depression and upregulated autoantibodies. The B6.Nba2 spontaneous mouse model develops SLE, but has not previously been tested for NPSLE.We investigated the NPSLE phenotype in male and female B6.Nba2 mice (n = 12 each) and age- and sex-matched B6 controls (n = 10 each) via behavioral assessments for anxiety, depression, and memory deficits. Serum anti-dsDNA, anti-nRNP, anti-DWEYS peptide reactive IgG autoantibody levels and soluble TWEAK levels were determined by ELISA. Hippocampal regions were stained for activated microglia and neurons.Both male and female B6.Nba2 mice showed elevated anti-dsDNA IgG, anti-nRNP IgG and anti-DWEYS reactive antibodies, elevated serum soluble TWEAK levels, and a strong anxiety and depression phenotype (p 0.05-0.0001). Male B6.Nba2 mice developed this phenotype at a slightly older age than females. Female B6.Nba2 mice displayed reduced numbers of neurons in the hippocampal region compared to female B6 controls (p 0.05).The B6.Nba2 mouse model recapitulates many known NPSLE phenotypes, making it a promising model to investigate the development of NPSLE in the context of SLE.

Obesity affects more than one-third of adults in the U.S., and effective treatment options are urgently needed. Oxytocin administration induces weight loss in animal models of obesity via effects on caloric intake, energy expenditure, and fat metabolism. We study intranasal oxytocin, an investigational drug shown to reduce caloric intake in humans, as a potential novel treatment for obesity.We report the rationale, design, methods, and biostatistical analysis plan of a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin for weight loss (primary endpoint) in adults with obesity. Participants (aged 18-45 years) were randomly allocated (1:1) to oxytocin (four times daily over eight weeks) versus placebo. Randomization was stratified by biological sex and BMI (30 to35, 35 to40, ≥40 kg/mSixty-one male and female participants aged 18-45 years were randomized (mean age 34 years, mean BMI 37 kg/mInvestigating intranasal oxytocin's efficacy, safety, and mechanisms as an anti-obesity medication will advance the search for optimal treatment strategies for obesity and its associated severe sequelae.

Background Patient outcomes following health care interventions may be dependent on a variety of factors: patient, surgeon, hospital, information technology, and temporal, cultural, and socioeconomic factors, among others. In this study, we characterize the relative contribution of each of these factors using a model of 30-day readmission following coronary artery bypass graft. Methods The Healthcare Cost and Utilization Project, the American Hospital Association Annual Health Survey Databases, the Healthcare Information and Management Systems Society, and the Distressed Communities Index from 2010 to 2013 were linked for Florida, Iowa, Massachusetts, Maryland, New York, and Washington. Logistic regression, random forest, decision tree, gradient boosting, k-nearest-neighbors classification, and XGBoost tree models were implemented. Modeling results were compared on the basis of predictive accuracy, sensitivity, specificity, and area under the curve. Decision tree performed best and was selected for further analysis. A gradient-boosted model was used to quantify factor contribution. Results The model had 45,352 patients, 54,096 admissions, and a 16.2% 30-day readmission rate after coronary artery bypass graft. The top 10 predictors were disposition at discharge, number of chronic conditions, total procedures, median household income, adults without high school diplomas, primary payer method, Agency for Healthcare Research and Quality comorbidity: renal failure, patient location (urban-rural), admission type, and age categories. The top 3 socioeconomic predictors were estimated state median household income, adults without high school diplomas, and patient location (urban versus rural designation). The relative contribution of patient/temporal, socioeconomic, hospital information technology, and hospital factors to readmission is 83.45%, 5.71%, 6.34%, and 4.31%, respectively. Conclusion In this model, the contribution of socioeconomic factors is substantive but lags significantly behind patient/temporal factors. With ever increasing availability of data, identification of contributors to patient outcomes within the overall health care macroenvironment will allow prioritization of interventions.

Substance use and psychopathology symptoms increase in adolescence. One key risk factor for these is high parent stress. Mindfulness interventions reduce stress in adults and may be useful to reduce parent stress and prevent substance use (SU) and psychopathology in adolescents. This study tested the feasibility and effects of a mindfulness intervention for parents on adolescent SU and psychopathology symptoms. Ninety-six mothers of 11–17 year olds were randomly assigned to a mindfulness intervention for parents (the Parenting Mindfully [PM] intervention) or a brief parent education [PE] control group. At pre-intervention, post-intervention, 6-month follow-up, and 1-year follow-up, adolescents reported on SU and mothers and adolescents reported on adolescent externalizing and internalizing symptoms. Primary intent to treat analyses found that the PM intervention prevented increases in adolescent SU over time, relative to the PE control group. The PM intervention also prevented increases in mother-reported externalizing symptoms over time relative to the PE control group. However, PM did not have a significant effect on internalizing symptoms. PM had an indirect effect on adolescent-reported externalizing symptoms through greater mother mindfulness levels at post-intervention, suggesting mother mindfulness as a potential intervention mechanism. Notably, while mothers reported high satisfaction with PM, intervention attendance was low (31% of mothers attended zero sessions). Secondary analyses with mothers who attended > = 50% of the interventions (n = 48) found significant PM effects on externalizing symptoms, but not SU. Overall, findings support mindfulness training for parents as a promising intervention and future studies should work to promote accessibility for stressed parents. Clinical Trials Identifier: NCT02038231; Date of Registration: January 13, 2014

OBJECTIVES: To describe the characteristics of hospitalized children with severe acute respiratory syndrome coronavirus 2 in New York City metropolitan area. PATIENTS AND METHODS: This was a multicenter, retrospective cohort study at 4 hospitals comprising 82 hospitalized children (0–21 years) who tested positive for severe acute respiratory syndrome coronavirus 2 after symptoms and risk screening between March 1 and May 10, 2020. We subdivided patients on the basis of their admission to acute or critical care units and by age groups. Further subanalyses were performed between patients requiring respiratory support or no respiratory support. RESULTS: Twenty-three (28%) patients required critical care. Twenty-nine (35%) patients requiring respiratory support, with 9% needing mechanical ventilation, and 1 required extracorporeal support. All patients survived to discharge. Children with any comorbidity were more likely to require critical care (70% vs 37%, P = .008), with obesity as the most common risk factor for critical care (63% vs 28%, P = .02). Children with asthma were more likely to receive respiratory support (28% vs 8%, P = .02), with no difference in need for critical care (P = .26). Children admitted to critical care had higher rates of renal dysfunction at presentation (43% vs 10%, P = .002). CONCLUSIONS: Children with comorbidities (obesity and asthma in particular) were at increased risk for critical care admission and/or need for respiratory support. Children with renal dysfunction at presentation were more likely to require critical care.

Endovascular aortic aneurysm repair of complex aortic aneurysms requires incorporation of side branches using specially designed aortic stent grafts with fenestrations, directional branches, or parallel stent grafts. These techniques have been increasingly used and reported in the literature. The purpose of this document is to clarify and to update terminology, classification systems, measurement techniques, and end point definitions that are recommended for reports dealing with endovascular repair of complex abdominal and thoracoabdominal aortic aneurysms involving the renal and mesenteric arteries.

OBJECTIVES The cause of ischemic stroke remains unknown, cryptogenic, in 25% of young and middle-aged patients. We hypothesized that if atherosclerosis is prominent in cryptogenic stroke, it would have a similar proinflammatory protein signature as large artery atherosclerosis (LAA) stroke. MATERIALS & METHODS Blood was collected in the acute phase and after 3 months from cryptogenic (n = 162) and LAA (n = 73) stroke patients aged 18-69 years and once from age-matched controls (n = 235). Cryptogenic stroke was divided into Framingham Risk Score (FRS) quartiles to compare low and high risk of atherosclerosis. Plasma concentrations of 25 proteins were analyzed using a Luminex multiplex assay. The discriminating properties were assessed with discriminant analysis and C-statistics. RESULTS We identified proteins that separated cryptogenic and LAA stroke from controls (area under the curves, AUCs ≥ 0.85). For both subtypes, RANTES, IL-4, and IFN-γ contributed the most at both time points. These associations were independent of risk factors of atherosclerosis. We also identified proteins that separated cryptogenic strokes in the lowest quartile of FRS from those in the highest, and from LAA stroke (AUCs ≥ 0.76), and here eotaxin and MCP-1 contributed the most. CONCLUSIONS The protein signature separating cases from controls was different from the signature separating cryptogenic stroke with low risk of atherosclerosis from those with high risk and from LAA stroke. This suggests that increased RANTES, IL-4, and IFN-γ in stroke may not be primarily related to atherosclerosis, whereas increased eotaxin and MCP-1 in cryptogenic stroke may be markers of occult atherosclerosis as the underlying cause.

Background Reduced cortical sensorimotor inhibition is associated with mobility and cognitive impairments in people with Parkinson’s disease (PD) and older adults (OAs). However, there is a lack of clarity regarding the relationships among sensorimotor, cognitive, and mobility impairments. The purpose of this study was to determine how cortical sensorimotor inhibition relates to impairments in mobility and cognition in people with PD and OAs. Method Cortical sensorimotor inhibition was characterized with short-latency afferent inhibition (SAI) in 81 people with PD and 69 OAs. Six inertial sensors recorded single- and dual-task gait and postural sway characteristics during a 2-minute walk and a 1-minute quiet stance. Cognition was assessed across the memory, visuospatial, executive function, attention, and language domains. Results SAI was significantly impaired in the PD compared to the OA group. The PD group preformed significantly worse across all gait and postural sway tasks. In PD, SAI significantly correlated with single-task foot strike angle and stride length variability, sway area, and jerkiness of sway in the coronal and sagittal planes. In OAs, SAI significantly related to single-task gait speed and stride length, dual-task stride length, and immediate recall (memory domain). No relationship among mobility, cognition, and SAI was observed. Conclusions Impaired SAI related to slower gait in OA and to increased gait variability and postural sway in people with PD, all of which have been shown to be related to increased fall risk.

DNA methylation has become increasingly recognized in the etiology of complex diseases, including thrombotic disorders. Blood is often collected in epidemiological studies for genotyping and has recently also been used to examine DNA methylation in epigenome-wide association studies. DNA methylation patterns are often tissue-specific, thus, peripheral blood may not accurately reflect the methylation pattern in the tissue of relevance. Here, we collected paired liver and blood samples concurrently from 27 individuals undergoing liver surgery. We performed targeted bisulfite sequencing for a set of 35 hemostatic genes primarily expressed in liver to analyze DNA methylation levels of >10,000 cytosine-phosphate-guanine (CpG) dinucleotides. We evaluated whether DNA methylation in blood could serve as a proxy for DNA methylation in liver at individual CpGs. Approximately 30% of CpGs were nonvariable and were predominantly hypo- (70%) in both tissues. While blood can serve as a proxy for liver at these CpGs, the low variability renders these unlikely to explain phenotypic differences. We therefore focused on CpG sites with variable methylation levels in liver. The level of blood–liver tissue correlation varied widely across these variable CpGs; moderate correlations (0.5 ≤ r

Delayed-immediate, or "babysitter," deep inferior epigastric perforator (DIEP) flap reconstruction, defined as immediate tissue expander or implant placement at the time of mastectomy followed by eventual exchange for DIEP flap, is becoming increasingly popular in breast cancer patients anticipated to receive adjuvant radiotherapy. In this study, we aim to compare delayed-immediate to immediate DIEP flap patients in postoperative outcomes including major complications and surgical site morbidity.A retrospective cohort study between immediate and delayed-immediate DIEP flap patients was performed. Patient demographics, comorbidities, and preoperative cancer treatment were compared between the 2 cohorts. Clinical outcomes of interest included dehiscence, necrosis, and infection of the breast, abdomen, and umbilicus in the 90-day postoperative period as well as breast hematoma, anastomotic failure, flap loss, and venous thromboembolism.Of the 248 patients (443 breasts) included in this study, 193 women (344 breasts) and 55 women (99 breasts) were in the immediate and delayed-immediate cohorts, respectively. The 2 cohorts were comparable in age, body mass index, and comorbidities (P0.05). Despite significantly higher rates of preoperative cancer treatment (P0.05), delayed-immediate patients were not at an elevated risk for major complications. The 2 cohorts were also comparable in surgical site outcomes, with the exception of breast skin necrosis, which was significantly higher in incidence in the immediate cohort (16.0% vs 2.0%, P0.001).This study is the first to directly compare delayed-immediate to immediate DIEP flap reconstruction in postoperative outcomes. Our findings show that babysitter DIEP flaps are a safe option for patients, even in those expected to undergo breast irradiation preoperatively.

Right iliac fossa (RIF) pain is a common indication for laparoscopy to diagnose and treat appendicitis. When a macroscopically normal appendix is found, there is no standard consensus regarding excision. Some surgeons remove the appendix due to the risk of microscopic inflammation and to avoid a future, repeat laparoscopy for possible appendicitis. Alternatively, others leave the appendix in situ to avoid morbidity from a potentially unnecessary procedure. We aimed to evaluate the outcomes of patients with macroscopically normal appendices left in situ.All emergency laparoscopies without appendicectomy between January 1st 2010- December 31st 2020 were identified from theatre records. All operative notes were individually evaluated and comments on the macroscopic appearance of the appendix and any intra-operative pathology were recorded. Only patients undergoing laparoscopy for suspected appendicitis with macroscopically normal appendices were included.A total of 120 patients [median age 21.68 (range 9-90.8) years] were included. The cohort was predominantly female (n=105, 87.5%). Forty-eight patients (40.0%) had a positive finding during index laparoscopy. During a median duration of 94.5 (range 8-131) months' follow-up, 16 patients (13.33%) underwent a repeat laparoscopy for recurrent RIF pain. Thirteen (10.8% of total cohort) subsequently underwent an appendicectomy. Histology confirmed acute appendicitis in six cases (4.17% of entire cohort). On subanalysis of smaller cohort, index laparoscopies with no positive findings (n=72), nine patients (12.5%) underwent appendicectomy with two (2.7%) appendices demonstrating appendicitis on histological examination.87% of the total cohort with a normal appendix at laparoscopy for RIF pain did not undergo further laparoscopy. Less than 5% of the total cohort and 2.7% of subanalysis cohort had an appendicectomy for histologically-proven appendicitis within the follow-up period. From the evidence in this study, we conclude that leaving the appendix in situ unless macroscopically inflamed is a viable alternative to excision.

Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients.In this phase 1-2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 μg, Ad26.COV2.S (JohnsonJohnson-Janssen) at a dose of 5×10Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients.Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209.).

We studied domestic ferrets (Mustela putorius furo) to evaluate the physiologic effects of routine surgery. Standard plasma biochemistry panels and 1H-NMR spectroscopy of heparinized whole blood were performed on samples taken 24 h prior to and immediately after surgery from female and male ferrets undergoing routine gonadectomy. Increases in plasma glucose, phosphorus, potassium, and creatine kinase concentrations associated with the duration of surgery were identified on plasma biochemistry panels. Whole-blood NMR spectra allowed us to identify 42 metabolites and one drug residue. Variations between pre- and postoperative metabolite concentrations were most pronounced for female ferrets, which underwent more prolonged surgery than males. Affected metabolites included organic acids and osmolytes (betaine, methylmalonate, D-lactate), fatty acids and lipids (2-hydroxy-3-methylbutyric acid), and amino acid groups (acetylglycine, alloisoleucine, leucine, and isoleucine). These findings indicate that 1H-NMR spectroscopy of whole blood provides insight into metabolic perturbations in domestic ferrets undergoing surgery that are not detected in routine clinical chemistry panels.