Search

To determine the optimal combination of imaging and biochemical biomarkers for use in the prediction of knee osteoarthritis (OA) progression.The present study was a nested case-control trial from the Foundation of the National Institutes of Health OA Biomarkers Consortium that assessed study participants with a Kellgren/Lawrence grade of 1-3 who had complete biomarker data available (n = 539 to 550). Cases were participants' knees that had radiographic and pain progression between 24 and 48 months compared to baseline. Radiographic progression only was assessed in secondary analyses. Biomarkers (baseline and 24-month changes) that had a P value of0.10 in univariate analysis were selected, including quantitative cartilage thickness and volume on magnetic resonance imaging (MRI), semiquantitative MRI markers, bone shape and area, quantitative meniscal volume, radiographic progression (trabecular bone texture [TBT]), and serum and/or urine biochemical markers. Multivariable logistic regression models were built using 3 different stepwise selection methods (complex models versus parsimonious models).Among baseline biomarkers, the number of locations affected by osteophytes (semiquantitative), quantitative central medial femoral and central lateral femoral cartilage thickness, patellar bone shape, and semiquantitative Hoffa-synovitis predicted OA progression in most models (C statistic 0.641-0.671). In most models, 24-month changes in semiquantitative MRI markers (effusion-synovitis, meniscal morphologic changes, and cartilage damage), quantitative central medial femoral cartilage thickness, quantitative medial tibial cartilage volume, quantitative lateral patellofemoral bone area, horizontal TBT (intercept term), and urine N-telopeptide of type I collagen predicted OA progression (C statistic 0.680-0.724). A different combination of imaging and biochemical biomarkers (baseline and 24-month change) predicted radiographic progression only, which had a higher C statistic of 0.716-0.832.The present study highlights the combination of biomarkers with potential prognostic utility in OA disease-modifying trials. Properly qualified, these biomarkers could be used to enrich future trials with participants likely to experience progression of knee OA.

ObjectiveTo develop a simple and effective risk score for predicting which stroke patients will have persistent impairment of upper extremity motor function at 90 days.DesignPost hoc analysis of clinical trial patients hospitalized with acute ischemic stroke who were followed for 90 days to determine functional outcome.SettingPatient were hospitalized at facilities across the United States.ParticipantsWe created a harmonized cohort of individual patients (N=1653) from the NINDS tPA, ALIAS part 2, IMS-III, DEFUSE 3, and FAST-MAG trials. We split the cohort into balanced derivation and validation samples.InterventionsNot applicable.Main outcome measuresThe primary outcome was persistent arm impairment, defined as a National Institutes of Health Stroke Scale (NIHSS) arm domain score of 2 to 4 at 90 days in patients who had a 24-hour NIHSS arm score of 1 or more. We used least absolute shrinkage and selection operator regression to determine the elements of the persistent upper extremity impairment (PUPPI) index, which we validated as a predictive tool.ResultsWe included 1653 patients (827 derivation, 826 validation), of whom 803 (48.6%) had persistent arm impairment. The PUPPI index gives 1 point each for age 55 years or older and NIHSS values of worse arm (4), worse leg (>2), facial palsy (3), and total NIHSS (≥10). The optimal cutpoint for the PUPPI index was 3 or greater, at which the area under the curve was greater than 0.75 for the derivation and validation cohorts and when using NIHSS values from either 24 hours or in a subacute or discharge time window. Results were similar across different levels of stroke severity.ConclusionThe PUPPI index uses readily available information to accurately predict persistent upper extremity motor impairment at 90 days poststroke. The PUPPI index can be administered in minutes and could be used as inclusion criterion in recovery-related clinical trials or, with additional development, as a prognostic tool for patients, caregivers, and clinicians.

Objective Older adults are one of the fastest growing age groups seeking emergency care for suicidal ideation and self-harm. Timely follow-up outpatient mental healthcare is important to suicide prevention, yet little is known about predictors of care continuity following hospital discharge. This study identified patient-, hospital-, and regional-level factors associated with 7-day follow-up outpatient mental healthcare in suicidal older adults. Methods Retrospective cohort analysis using 2015 Medicare data for adults aged ≥65 years hospitalized for suicidal ideation, suicide attempt, or deliberate self-harm (n = 27,257) linked with the American Hospital Association survey and Area Health Resource File. Rates and adjusted risk ratios stratified by patient, hospital, and regional variables were assessed for 7-day follow-up outpatient mental healthcare. Results Overall, 30.3% of patients received follow-up mental healthcare within 7 days of discharge. However, follow-up rates were higher for patients with any mental healthcare within 30 days prehospitalization (43.7%) compared to patients with no recent mental healthcare (15.7%). Longer length of stay and care in psychiatric hospitals were associated with higher odds of follow-up. For patients with no mental healthcare in the 30 days prehospitalization, discharge from hospitals that were large, system-affiliated, academic medical centers, or provided hospitalist-based care were associated with lower odds of follow-up. Females were more likely to receive 7-day follow-up, whereas non-white patients were less likely to receive follow-up care. Conclusion Timely follow-up is influenced by multiple patient, hospital, and community characteristics. Findings highlight the need for quality improvement to promote successful transitions from inpatient to outpatient care.

BACKGROUND There is an ongoing debate about whether neoadjuvant radiation therapy is associated with higher rates of postoperative complications after head and neck reconstruction. Herle et al. conducted a systematic review in 2014 of 24 studies, finding higher complication rates in irradiated fields. We sought to perform an exhaustive updated systematic review and meta-analysis. METHODS We conducted an updated systematic review of the literature, as outlined in our protocol, which was registered on PROSPERO. Databases included Medline, Embase, Cochrane Central, and Web of Science. There were no limits placed on the date range, place of publication, or origin. Exclusion criteria included patients less than 18 years of age, studies with less than 20 participants (n < 20), case studies, skull base reconstructions, and local tissue rearrangements. The combined results of the studies and relative risks (RR) were calculated. RESULTS 53 studies were included for analysis, including 5,086 free flaps in an irradiated field, and 9,110 free flaps in a non-irradiated field. Of the 53 studies, 21 studies overlapped with those discussed in Herle et al.'s study, with a total of 32 additional studies. Neoadjuvant radiation was found to be a statistically significant risk factor for postoperative complications (RR 1.579, P < 0.001), total flap failure (RR, 1.565; P < 0.001), and fistula (RR, 1.810; P < 0.001). Our work reaffirmed the findings of the Herle et al. STUDY CONCLUSION Preoperative radiation was associated with a statistically significant increase in the risk of total flap failure, fistula, and total complications but not partial flap failure. These high-morbidity complications must be taken into consideration when determining which patients should receive neoadjuvant radiation therapy.

BACKGROUND: Obesity is correlated with many biomarkers, but the extent to which these correlate with underlying body composition is poorly understood. OBJECTIVES: Our objectives were to 1) describe/compare distinct contributions of fat/lean mass with BMI–metabolite correlations and 2) identify novel metabolite biomarkers of fat/lean mass. METHODS: The Alberta Physical Activity and Breast Cancer Prevention Trial was a 2-center randomized trial of healthy, inactive, postmenopausal women (n = 304). BMI (in kg/m(2)) was calculated using weight and height, whereas DXA estimated fat/lean mass. Ultra-performance liquid chromatography and mass spectrometry measured relative concentrations of serum metabolite concentrations. We estimated partial Pearson correlations between 1052 metabolites and BMI, adjusting for age, smoking, and site. Fat mass index (FMI; kg/m(2)) and lean mass index (LMI; kg/m(2)) correlations were estimated similarly, with mutual adjustment to evaluate independent effects. RESULTS: Using a Bonferroni-corrected α level 0.20), 25 modestly (0.10 ≤ |r| ≤ 0.20), and 7 virtually null (|r| < 0.10). Ten of 53 were more strongly correlated with LMI than with FMI. Examining non–BMI-correlated metabolites, 6 robustly correlated with FMI (|r| = 0.24–0.31) and 2 with LMI (r = 0.25–0.26). For these, correlations for fat and lean mass were in opposing directions compared with BMI-correlated metabolites, in which correlations were mostly in the same direction. CONCLUSIONS: Our results demonstrate how a thorough evaluation of the components of fat and lean mass, along with BMI, provides a more accurate assessment of the associations between body composition and metabolites than BMI alone. Such an assessment makes evident that some metabolites correlated with BMI predominantly reflect lean mass rather than fat, and some metabolites related to body composition are not correlated with BMI. Correctly characterizing these relations is important for an accurate understanding of how and why obesity is associated with disease.

Purpose We aim to assess the healthcare value achieved from a shared savings program for pediatric appendectomy. Methods All appendectomy patients covered by our health plan were included. Quality targets were 15% reduction in time to surgery, length of stay, readmission rate, and patient satisfaction. Quality targets and costs for an appendectomy episode in two 6-month performance periods (PP1, PP2) were compared to baseline. Results 640 patients were included (baseline:317, PP1:167, PP2:156). No quality targets were met in PP1. Two quality targets were met during PP2: readmission rate (−57%) and patient satisfaction. No savings were realized because the cost reduction threshold (−9%) was not met during PP1 (+1.7%) or PP2 (−0.4%). Conclusions Payer-provider partnerships can be a platform for testing value-based reimbursement models. Setting achievable targets, identifying affectable quality metrics, considering case mix index, and allowing sufficient time for interventions to generate cost savings should be considered in future programs.

PURPOSE/OBJECTIVE(S) To determine if patients with unfavorable intermediate-risk (UIR), high-risk (HR), or very high-risk (VHR) prostate cancer (PCa) treated with 125I interstitial brachytherapy benefit from androgen deprivation therapy (ADT). MATERIALS/METHODS We reviewed our institutional database of patients with UIR, HR, or VHR PCa, per 2018 NCCN risk classification, treated with definitive 125I interstitial brachytherapy with or without ADT from 1998-2017. Outcomes including biochemical failure (bF), distant metastases (DM), and overall survival (OS) were analyzed with the Kaplan-Meier method and Cox proportional hazards regression. PCa-specific mortality (PCSM) was analyzed with Fine-Gray competing-risk regression. RESULTS Of 1033 patients, 262 (25%) received ADT and 771 (75%) did not. Median ADT duration was 6 months. By risk group, 764 (74%) patients were UIR, 219 (21%) HR, and 50 (5%) VHR. ADT was more frequently given to HR (50%) and VHR (56%) patients compared to UIR (16%; p

Purpose: This study assessed the efficacy, safety, and pharmacokinetics of adavosertib in combination with four chemotherapy agents commonly used in patients with primary platinum-resistant ovarian cancer. Patients and Methods: Women with histologically or cytologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer with measurable disease were enrolled between January 2015 and January 2018 in this open-label, four-arm, multicenter, phase II study. Patients received adavosertib (oral capsules, 2 days on/5 days off or 3 days on/4 days off) in six cohorts from 175 mg once daily to 225 mg twice daily combined with gemcitabine, paclitaxel, carboplatin, or pegylated liposomal doxorubicin. The primary outcome measurement was overall response rate. Results: Three percent of patients (3/94) had confirmed complete response and 29% (27/94) had confirmed partial response. The response rate was highest with carboplatin plus weekly adavosertib, at 66.7%, with 100% disease control rate, and median progression-free survival of 12.0 months. The longest median duration of response was in the paclitaxel cohort (12.0 months). The most common grade ≥3 adverse events across all cohorts were neutropenia [45/94 (47.9%) patients], anemia [31/94 (33.0%)], thrombocytopenia [30/94 (31.9%)], and diarrhea and vomiting [10/94 (10.6%) each]. Conclusions: Adavosertib showed preliminary efficacy when combined with chemotherapy. The most promising treatment combination was adavosertib 225 mg twice daily on days 1–3, 8–10, and 15–17 plus carboplatin every 21 days. However, hematologic toxicity was more frequent than would be expected for carboplatin monotherapy, and the combination requires further study to optimize the dose, schedule, and supportive medications.

OBJECTIVE To analyze predictors, extent and functional implications associated with renal parenchymal volume replacement (PVR) by renal cell carcinoma (RCC) prior to intervention. This phenomenon is well-recognized yet not adequately studied, and, if severe, can influence management. MATERIALS AND METHODS A retrospective review was performed of partial nephrectomy (PN) and radical nephrectomy (RN) patients with available preoperative nuclear-renal-scan and imaging demonstrating solitary RCC with normal contralateral kidney. Normal renal parenchymal volume of each kidney was measured by free-hand scripting from preoperative axial images. Primary endpoint was percent PVR which was estimated assuming that the contralateral-kidney serves as a control: PVR = (volume contralateral kidney - volume ipsilateral kidney) normalized by volume contralateral kidney. Multivariable linear-regression analysis assessed factors associated with preoperative PVR. Further analysis evaluated the functional effect of PVR prior to surgery. RESULTS 146 PN and 136 RN patients with necessary studies were analyzed. For RN, the median PVR was 15% and a quarter of patients had PVR ≥27%. In contrast, PVR was negligible in PN patients for whom median preoperative parenchymal volumes were nearly identical in the ipsilateral/contralateral kidneys (179/180cc, respectively). PVR inversely correlated with preoperative renal function in the ipsilateral kidney (P

Background: Bariatric surgery leads to long-term remission and reduced incidence of diabetes, hypertension, and dyslipidemia. Short-term studies suggest reduction in specific fat depots may be more predictive of health improvement than reduced body mass index (BMI). Visceral, subcutaneous, epicardial, and liver fat, measured 11 years after bariatric surgery, were associated with long-term remission and incidence of diabetes, dyslipidemia, and hypertension. Methods: Fat depots an average of 11 (maximum 14) years after surgery were quantified by noncontrast computed tomography in subjects who did (N = 261; 86% gastric bypass) or did not (N = 243) have bariatric surgery. Multiple regression related fat depots to disease endpoints with and without adjustment for change in BMI and surgical status. Results: Visceral fat was 42% lower, subcutaneous fat 20% lower, epicardial fat 30% lower, and liver-to-spleen density ratio 9% higher at follow-up in the bariatric surgery group compared with the nonsurgery group (all P

Background Although several Utstein variables are known to independently improve survival, how they moderate the effect of emergency medical service (EMS) response times on survival is unknown. Objectives To quantify how public location, witnessed status, bystander CPR, and bystander AED shock individually and jointly moderate the effect of EMS response time delays on OHCA survival. Methods This retrospective cohort study was a secondary analysis of the Resuscitation Outcomes Consortium Epistry-Cardiac Arrest database (December 2005 to June 2015). We included all adult, non-traumatic, non-EMS witnessed, and EMS-treated OHCAs from eleven sites across the US and Canada. We trained a logistic regression model with standard Utstein control variables and interaction terms between EMS response time and the four aforementioned OHCA characteristics. Results 102,216 patients were included. Three of the four characteristics – witnessed OHCAs (OR = 0.962), bystander CPR (OR = 0.968) and public location (OR = 0.980) – increased the negative effect of a one-minute delay on the odds of survival. In contrast, a bystander AED shock decreased the negative effect of a one-minute response time delay on the odds of survival (OR = 1.064). The magnitude of the effect of a one-minute delay in EMS response time on the odds of survival ranged from 1.3% to 9.8% (average: 5.3%), depending on the underlying OHCA characteristics. Conclusions Delays in EMS response time had the largest reduction in survival odds for OHCAs that did not receive a bystander AED shock but were witnessed, occurred in public, and/or received bystander CPR. A bystander AED shock appears to be protective against a delay in EMS response time.

INTRODUCTION Studies have shown the benefit of intensive care unit (ICU) bundled protocols; however, they are primarily derived from medical patients. We hypothesized that patients and their medication profiles are different between critically ill medical, surgical, and trauma patients. METHODS The Pediatric Health Information System 2017 dataset was used to perform a retrospective cohort study of critically ill children. The pediatric medical, surgical, and trauma cohorts were separated based on ICD-10 codes. Data collected included demographics, secondary diagnoses, outcomes, and medication data. Medications were grouped as opiates, GABA-agonists, alpha-2 agonists, anti-psychotics, paralytics, and "other" sedatives. A non-parametric Kolmogorov-Smirnov test (KS test) and odds ratios (reference group: medical cohort) were calculated to compare medication administration between the study cohorts for the first 30 ICU days. RESULTS A total of 4488 critically ill children (medical 2078, surgical 1650, and trauma 760) were identified. The trauma cohort had increased incidence of delirium (medical 10.8%, surgical 11.5%, trauma 13.8%; p 50% received GABA-agonists on ICU days 0-30. With the KS test, there was a significant difference in administration of opiates, GABA-agonists, alpha-2 agonists, anti-psychotics, and "other" sedatives over the first 30 days in the ICU. Relative to medical patients, trauma patients had significantly higher odds of receiving anti-psychotics on ICU days 10-20 and 22-24. CONCLUSION Critically ill pediatric trauma, medical, and surgical patients are distinctly different patient populations with differing pharmacologic profiles for analgesia, sedation, and delirium. LEVEL OF EVIDENCE Level III (Retrospective Comparative Study).

Background The American College of Surgeon (ACS), American Surgical Association (ASA), Association of Women Surgeons (AWS), and Society of Black Academic Surgeons (SBAS) partnered to gain insight into whether inequities found in surgical society presidents may be present earlier. Methods ACS, ASA, AWS, and SBAS presidents’ CVs were assessed for demographics and scholastic achievements at the time of first faculty appointment. Regression analyses controlling for age were performed to determine relative differences across societies. Results 66 of the 68 presidents’ CVs were received and assessed (97% response rate). 50% of AWS future presidents were hired as Instructors rather than Assistant professors, compared to 29.4% of SBAS, 25% of ASA and 29.4% of ACS. The future ACS, ASA, and SBAS presidents had more total publications than the AWS presidents, but similar numbers of 1st and Sr. author publications. Conclusion Gender inequities in academic surgeon hiring practices and perceived scholastic success may be present at first hire.

Objective To describe the practice patterns and outcomes of patients with stage 3B endometrial cancer. Methods We queried the National Cancer Database for all surgically staged, stage 3 patients between 2012 and 2016. Patients who received any pre-operative therapy were excluded. Demographics, tumor factors, and adjuvant therapy for the stage 3 substages were compared. Logistic regression was used to identify factors associated with adjuvant therapy. Kaplan Meier curves were generated and compared using the log-rank test. Multivariable Cox Proportional Hazards Model was used to adjust for prognostic factors. Findings with p Results Of 7363 patients with stage 3 disease, 478 (6%) had stage 3B; 1732 (23%) had stage 3A, 3457 (48%) had stage 3C1, and 1696 (23%) had stage 3C2 disease. Post-surgical treatment consisted of: combined chemotherapy (CT) and radiation (RT) (49%), CT alone (28%), RT alone (9%), 14% received no postoperative therapy. Among all stage 3 substages, patients with stage 3B disease were the least likely to receive any CT, and the most likely to receive RT alone. After adjusting for known prognostic factors, patients with stage 3A (Hazard ratio (HR) of death = 0.64) and 3C1 (HR of death = 0.79) disease had significantly worse overall survival compared to stage 3B; survival was not demonstrably different from patients with stage 3C2 disease. Patients with stage 3B disease who received CT + RT had the best overall survival. Conclusion Survival of patients with stage 3B disease is similar to that of patients with para-aortic node metastases and is inferior to all others with stage 3 endometrial cancer. Less frequent CT and a higher rate of post-operative RT alone, describes a distinct practice from that seen in other stage 3 patients.

Background Z scores are the method of choice to report dimensions in pediatric echocardiography. Z scores based on body surface area (BSA) have been shown to cause systematic biases in overweight and obese children. Using aortic valve (AoV) diameters as a paradigm, the aims of this study were to assess the magnitude of z score underestimation in children with increased body mass index z score (BMI-z) and to determine if a predicting model with height and weight as independent predictors would minimise this bias. Methods In this multicentre, retrospective, cross-sectional study, 15,006 normal echocardiograms in healthy children 1-18 years old were analyzed. Residual associations with body size were assessed for previously published z score. BSA-based and alternate prediction models based on height and weight were developed and validated in separate training and validation samples. Results Existing BSA-based z scores incompletely adjusted for weight, BSA, and BMI-z and led to an underestimation of > 0.8 z score units in subjects with higher BMI-z compared with lean subjects. BSA-based models led to overestimation of predicted AoV diameters with increasing weight or BMI-z. Models using height and weight as independent predictors improved adjustment with body size, including in children with higher BMI-z. Conclusions BSA-based models result in underestimation of z scores in patients with high BMI-z. Prediction models using height and weight as independent predictors minimise residual associations with body size and generate well fitted predicted values that could apply to all children, including those with low or high BMI-z.

Regionalization of rectal cancer surgery may lead to worse disease free survival owing to longer travel time to reach a high volume center yet no study has evaluated this relationship at a single high volume center volume center.This was a retrospective review of rectal cancer patients undergoing surgery from 2009 to 2019 at a single high volume center. Patients were divided into two groups based on travel time. The primary outcome was disease-free survival (DFS). Additional outcomes included treatment within 60 d of diagnosis, completeness of preoperative staging, and evaluation by a colorectal surgeon prior to initiation of treatment.A lower proportion of patients with long travel time began definitive treatment within 60 d of diagnosis (74.0% versus 84.0%, P= 0.01) or were seen by the treating colorectal surgeon before beginning definitive treatment (74.8% versus 85.4%, P0.01). On multivariable logistic regression analysis, patients with long travel time were significantly less likely to begin definitive treatment within 60 d of diagnosis (OR = 0.54; 95% CI = 0.31-0.93) or to be evaluated by a colorectal surgeon prior to initiating treatment (OR = 0.45; 95% CI = 0.25-0.80). There were no significant differences in DFS based on travel time.Although patients with long travel times may be vulnerable to delayed, lower quality rectal cancer care, there is no difference in DFS when definitive surgery is performed at a high volume canter. Ongoing research is needed to identify explanations for delays in treatment to ensure all patients receive the highest quality care.

Multiparametric magnetic resonance imaging (mpMRI) plays several valuable roles in preoperative staging of adenocarcinoma of the prostate gland, including detection of clinically significant disease, determination of extraglandular extension, and assessment of nodal disease. The Prostate Imaging Reporting and Data System (PI-RADS) establishes certain acceptable technical standards for mpMRI. These technical parameters allow for consistent image quality, enabling accurate detection and staging of disease; this in turn has significant implications for treatment recommendations. The prostate gland has a characteristic zonal anatomy, with cancers arising from the peripheral zone tending to demonstrate more aggressive histologic features. The acquisition of several sequences as part of mpMRI protocol allows for assessment of locoregional disease as well as regional and distant lymphadenopathy. The local staging of prostate cancer with mpMRI is reviewed in this article.

Introduction The Nuss procedure is the most common and preferred operative correction of pectus excavatum. Surgeon preference and patient factors can result in variations in Nuss procedure technique. We hypothesize that certain techniques are associated with increased risk of complications. Materials and Methods We performed a single-center retrospective review of Nuss operations from 2016 to 2020. Variations in intraoperative techniques included sternal elevator (SE) use, number of bars placed, and usage of bilateral stabilizing sutures. Patient demographics, intraoperative data, and postoperative outcomes were reported as median with interquartile ranges or percentages. Statistical significance (p Results Two hundred and sixty-five patients were identified. Patients repaired with two bars were older with a larger Haller index (HI). Patient demographics were not significantly different for SE or stabilizing suture use. Placement of two bars was associated with significantly increased risk of readmission. Similarly, SE use was associated with increased risk of pleural effusion and readmission. Finally, the use of bilateral stabilizing sutures resulted in less frequent slipped bars without statistical significance. Conclusion Older patients with a larger HI were more likely to need two bars placed to repair pectus excavatum. Placement of multiple bars and SE use are associated with significantly higher odds of certain complications.

For decades, cognitive and behavioral therapies (CBTs) have been tested in randomized controlled trials for specific psychiatric syndromes that were assumed to represent expressions of latent diseases. Although these protocols were more effective as compared to psychological control conditions, placebo treatments, and even active pharmacotherapies, further advancement in efficacy and dissemination has been inhibited by a failure to focus on processes of change. This picture appears now to be evolving, due both to a collapse of the idea that mental disorders can be classified into distinct, discrete categories, and to the more central attention given to processes of change in newer, so-called "third-wave" CBTs. Here we review the context for this historic progress and evaluate the impact of these newer methods and models, not as protocols for treating syndromes, but as ways of targeting an expanded range of processes of change. Five key features of "third-wave" therapies are underlined: a focus on context and function; the view that new models and methods should build on other strands of CBT; a focus on broad and flexible repertoires vs. an approach to signs and symptoms; applying processes to the clinician, not just the client; and expanding into more complex issues historically more characteristic of humanistic, existential, analytic, or system-oriented approaches. We argue that these newer methods can be considered in the context of an idiographic approach to process-based functional analysis. Psychological processes of change can be organized into six dimensions: cognition, affect, attention, self, motivation and overt behavior. Several important processes of change combine two or more of these dimensions. Tailoring intervention strategies to target the appropriate processes in a given individual would be a major advance in psychiatry and an important step toward precision mental health care.

Parental opioid use may negatively affect child health. However, the scope of existing knowledge in this area has not been mapped. We conducted a scoping review of articles (N=1188) describing vari...

To examine factors contributing to completion of a patient-reported outcome (PRO) measure in patients undergoing laser vision correction.Retrospective, population-based study.All patients who underwent primary laser vision correction with a target of plano from July 1, 2014, to June 30, 2016, at a large refractive surgery center.Patients were asked to complete a PRO measure at the time of their preoperative and months 1 and 3 postoperative visits. Characteristics between patients who attended and did not attend the follow-up visits and completed and did not complete the PRO measure were compared. A logistic regression was performed to identify factors associated with likelihood of follow-up and completion of PRO measure. An inverse probability censoring weighted model was created to account for selective loss to follow-up and used to adjust the PRO satisfaction measure.Completion of the PRO measure at 1 and 3 months.A total of 37 043 patients were identified. Of these, 20 501 completed a 1-month postoperative PRO measure and 10 474 completed a 3-month postoperative PRO measure. Patients completing a PRO measure were more likely to be older, be female, have had photorefractive keratectomy (PRK), have completed a preoperative PRO measure, and have had a preoperative hyperopic correction (P0.001 for all comparisons). For every line of postoperative uncorrected acuity worse than 20/16, the odds ratio of completing a PRO measure was 1.33 (95% confidence interval [CI], 1.30-1.36, P0.001) at 1 month and 1.29 (95% CI, 1.26-1.33, P 0.001) at 3 months. At 1 month, there was no difference between the raw and model-adjusted rates of satisfaction with vision, but at 3 months the adjusted rate was significantly higher than the raw rate.Patients with worse objective visual outcomes were more likely to complete PRO measures in this population-based study. In a setting with loss to follow-up, PRO measures require methods to address missing data for correct interpretation.

Hepatic splenosis, a rare entity, is the ectopic implantation of splenic tissue into the hepatic parenchyma, most often incidentally seen in patients with a history of splenic trauma and splenectomy. We present a unique case of hepatic splenosis in a patient with hemosiderosis and splenectomy following the incidental finding of hepatic masses on pretransplant imaging. Final diagnosis was made based on cross-sectional imaging characteristics matching that of the left upper quadrant splenules alone. We discuss common characteristics of hepatic splenosis on multiple modalities, the effect of iron deposition on the imaging characteristics of hepatic and splenic tissue and how that impacts the differential and diagnosis. This case highlights the unique imaging characteristics hepatic splenosis can have particularly in the setting of hemosiderosis. Hepatic splenosis imaging diagnosis has a significant advantage over tissue diagnosis in terms of decreased risk, time and cost.

Objective The goal of the 1-year Advanced Gastrointestinal (AGI) surgery fellowship is to train the general surgeon to perform advanced and complex operations that they had insufficient experience with in residency training. This study examines the case logs of AGI fellows that have completed Society for Surgery of the Alimentary Tract (SSAT)-sponsored Fellowship Council (FC)-accredited AGI fellowships to determine the role of these fellowships in providing complex gastrointestinal operative experience. Design/Participants Institutional Review Board-approved retrospective surgical case log analysis. Case logs of 60 AGI fellows in 12 different AGI fellowships from 2014 to 2019 were requested by the SSAT and provided in a de-identified format from the FC. Cases were categorized as colorectal surgery, anus, hernia-abdomen, hernia inguinal, esophagus-hiatal hernia, esophagus-Heller, pancreas, liver, bile duct, diagnostic/therapeutic esophagogastroduodenoscopy (EGD), diagnostic/therapeutic colonoscopy, thoracic esophagus, thoracic lung, spleen, thyroid, diaphragm, gastric, abdomen, adrenal/kidney, bariatric, diagnostic/therapeutic bronchoscopy, kidney/liver/pancreas transplant, and trauma. Results AGI fellows performed a mean of 345 cases per year (range: 184-558). Our results showed that 5 programs provided >30 colorectal cases, 6 provided >50 hernia (hernia-abdomen and hernia-inguinal) cases, 8 provided >25 hiatal hernia cases, 2 provided >100 endoscopy cases (diagnostic/therapeutic EGD and diagnostic/therapeutic colonoscopy), 6 provided >30 gastric cases, 3 provided >100 bariatric cases, 6 provided >10 pancreas cases, 3 provided >10 liver cases, and 4 provided >6 biliary cases. Conclusion SSAT-sponsored FC-accredited AGI fellowship programs provide a wide array of training in complex gastrointestinal surgeries. Most programs provide broad training in hiatal work, colorectal surgery, hepato-pancreato-biliary surgery, and abdominal wall reconstruction. This FC-accredited AGI training paradigm prepares trainees for broad-based complex abdominal surgery, an area that is sorely needed to augment insufficient experience in many general surgical training programs.

Neural oscillations may contain important information pertaining to stroke rehabilitation. This study examined the predictive performance of electroencephalography‐derived neural oscillations following stroke using a data‐driven approach. Individuals with stroke admitted to an inpatient rehabilitation facility completed a resting‐state electroencephalography recording and structural neuroimaging around the time of admission and motor testing at admission and discharge. Using a lasso regression model with cross‐validation, we determined the extent of motor recovery (admission to discharge change in Functional Independence Measurement motor subscale score) prediction from electroencephalography, baseline motor status, and corticospinal tract injury. In 27 participants, coherence in a 1–30 Hz band between leads overlying ipsilesional primary motor cortex and 16 leads over bilateral hemispheres predicted 61.8% of the variance in motor recovery. High beta (20–30 Hz) and alpha (8–12 Hz) frequencies contributed most to the model demonstrating both positive and negative associations with motor recovery, including high beta leads in supplementary motor areas and ipsilesional ventral premotor and parietal regions and alpha leads overlying contralesional temporal–parietal and ipsilesional parietal regions. Electroencephalography power, baseline motor status, and corticospinal tract injury did not significantly predict motor recovery during hospitalization (R 2 = 0–6.2%). Findings underscore the relevance of oscillatory synchronization in early stroke rehabilitation while highlighting contributions from beta and alpha frequency bands and frontal, parietal, and temporal–parietal regions overlooked by traditional hypothesis‐driven prediction models., This study examined the predictive performance of electroencephalography‐derived neural oscillations following stroke using a data‐driven approach. In 27 participants, EEG coherence in a 1–30 Hz band between leads overlying ipsilesional primary motor cortex and 16 leads over bilateral hemispheres predicted 61.8% of the variance in motor recovery.

To determine minimally clinically important differences (MCIDs) for Disability Rating Scale (DRS), Fugl-Meyer Upper Extremity Subscale (FM-UE), Fugl-Meyer Lower Extremity Subscale (FM-LE), and Fugl-Meyer Motor Scale (FMMS) in patients with chronic motor deficits secondary to traumatic brain injury (TBI).Retrospective analysis from the 1-year, double-blind, randomized, surgical sham-controlled, Phase 2 STEMTRA trial (NCT02416492), in which patients with chronic motor deficits secondary to TBI (N = 61) underwent intracerebral stereotactic implantation of modified bone marrow-derived mesenchymal stromal (SB623) cells. MCIDs for DRS, FM-UE, FM-LE, and FMMS were triangulated with distribution-based, anchor-based, and Delphi panel estimates.Triangulated MCIDs were: 1) -1.5 points for the Disability Rating Scale; 2) 6.2 points for the Fugl-Meyer Upper Extremity Subscale; 3) 3.2 points for the Fugl-Meyer Lower Extremity Subscale; and 4) 8.4 points for the Fugl-Meyer Motor Scale.For the first time in the setting of patients with chronic motor deficits secondary to TBI, this study reports triangulated MCIDs for: 1) DRS, a measure of global outcome; and 2) Fugl-Meyer Scales, measures of motor impairment. These findings guide the use of DRS and Fugl-Meyer Scales in the assessment of global disability outcome and motor impairment in future TBI clinical trials.

This AUA Guideline focuses on evaluation/counseling/management of adult patients with clinically-localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions.The Renal Mass and Localized Renal Cancer guideline underwent an update literature review which resulted in the 2021 amendment. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]).Great progress has been made regarding the evaluation/management of clinically-localized renal masses. These guidelines provide updated, evidence-based recommendations regarding evaluation/counseling including the evolving role of renal-mass-biopsy (RMB). Given great variability of clinical/oncologic/functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Options for intervention (partial-nephrectomy (PN), radical-nephrectomy (RN), and thermal-ablation (TA)) are reviewed including recent data about comparative-effectiveness/potential morbidities. Oncologic issues are prioritized while recognizing the importance of functional-outcomes for survivorship. Granular criteria for RN are provided to help reduce overutilization of RN while also avoiding imprudent PN. Priority for PN is recommended for clinical T1a lesions, along with selective utilization of TA, which has good efficacy for tumors≤3.0 cm. Recommendations for genetic-counseling have been revised and considerations for adjuvant-therapies are addressed. Active-surveillance and follow-up after intervention are discussed in an adjunctive article.Several factors require consideration during counseling/management of patients with clinically-localized renal masses including general health/comorbidities, oncologic-considerations, functional-consequences, and relative efficacy/potential morbidities of various management-strategies.

Prevention of premature death in patients with chronic epilepsy remains a major challenge. Multiple pathophysiologic factors have been implicated, with intense investigation of cardiorespiratory mechanisms. Up to four in five patients with chronic epilepsy exhibit cardiovascular comorbidities. These findings led us to propose the concept of an "epileptic heart," defined as "a heart and coronary vasculature damaged by chronic epilepsy as a result of repeated surges in catecholamines and hypoxemia leading to electrical and mechanical dysfunction." Among the most prominent changes documented in the literature are high incidence of myocardial infarction and arrhythmia, altered autonomic tone, diastolic dysfunction, hyperlipidemia, and accelerated atherosclerosis. This suite of pathologic changes prompted us to propose for the first time in this review a syndromic approach for improved clinical detection of the epileptic heart condition. In this review, we discuss the key pathophysiologic mechanisms underlying the candidate criteria along with standard and novel techniques that permit evaluation of each of these factors. Specifically, we present evidence of the utility of standard 12-lead, ambulatory, and multiday patch-based electrocardiograms, along with measures of cardiac electrical instability, including T-wave alternans, heart rate variability to detect altered autonomic tone, echocardiography to detect diastolic dysfunction, and plasma biomarkers for assessing hyperlipidemia and accelerated atherosclerosis. Ultimately, the proposed clinical syndromic approach is intended to improve monitoring and evaluation of cardiac risk in patients with chronic epilepsy to foster improved therapeutic strategies to reduce premature cardiac death.

The Genitourinary Pathology Society (GUPS) reviewed recent advances in renal neoplasia, particularly post-2016 World Health Organization (WHO) classification, to provide an update on existing entities, including diagnostic criteria, molecular correlates, and updated nomenclature. Key prognostic features for clear cell renal cell carcinoma (RCC) remain WHO/ISUP grade, AJCC/pTNM stage, coagulative necrosis, and rhabdoid and sarcomatoid differentiation. Accrual of subclonal genetic alterations in clear cell RCC including SETD2, PBRM1, BAP1, loss of chromosome 14q and 9p are associated with variable prognosis, patterns of metastasis, and vulnerability to therapies. Recent National Comprehensive Cancer Network (NCCN) guidelines increasingly adopt immunotherapeutic agents in advanced RCC, including RCC with rhabdoid and sarcomatoid changes. Papillary RCC subtyping is no longer recommended, as WHO/ISUP grade and tumor architecture better predict outcome. New papillary RCC variants/patterns include biphasic, solid, Warthin-like, and papillary renal neoplasm with reverse polarity. For tumors with 'borderline' features between oncocytoma and chromophobe RCC, a term "oncocytic renal neoplasm of low malignant potential, not further classified" is proposed. Clear cell papillary RCC may warrant reclassification as a tumor of low malignant potential. Tubulocystic RCC should only be diagnosed when morphologically pure. MiTF family translocation RCCs exhibit varied morphologic patterns and fusion partners. TFEB-amplified RCC occurs in older patients and is associated with more aggressive behavior. Acquired cystic disease (ACD) RCC-like cysts are likely precursors of ACD-RCC. The diagnosis of renal medullary carcinoma requires a negative SMARCB1 (INI-1) expression and sickle cell trait/disease. Mucinous tubular and spindle cell carcinoma (MTSCC) can be distinguished from papillary RCC with overlapping morphology by losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22. MTSCC with adverse histologic features shows frequent CDKN2A/2B (9p) deletions. BRAF mutations unify the metanephric family of tumors. The term "fumarate hydratase deficient RCC" ("FH-deficient RCC") is preferred over "hereditary leiomyomatosis and RCC syndrome-associated RCC". A low threshold for FH, 2SC, and SDHB immunohistochemistry is recommended in difficult to classify RCCs, particularly those with eosinophilic morphology, occurring in younger patients. Current evidence does not support existence of a unique tumor subtype occurring after chemotherapy/radiation in early childhood.

As more people receive coronavirus disease 2019 (COVID-19) vaccinations, the side effects of the vaccines will become more apparent. One reported side effect that has come to light is unilateral axillary lymphadenopathy ipsilateral to the vaccination site. In general, unilateral axillary lymphadenopathy has a broad differential including malignancy, infection, autoimmune disorder, and iatrogenic etiologies. We present a case of a previously healthy 38-year-old woman who received her first dose of Pfizer COVID-19 vaccination 3 days prior to presenting to the emergency department complaining of 2 weeks of abdominal pain and 20-pound unintentional weight loss. Unilateral axillary lymphadenopathy, ipsilateral to the vaccination site, was found on a contrast-enhanced computed tomography examination of the chest, abdomen, and pelvis. Subsequent diagnostic mammograms did not demonstrate evidence of malignancy; however, axillary ultrasound again revealed nonspecific lymphadenopathy. A short-term follow-up axillary ultrasound was recommended, rather than a lymph node biopsy, given the history of recent vaccination. At clinical follow-up, the patient's abdominal pain resolved and no further weight loss was noted. This case report discusses the key components and workup recommendation of unilateral axillary lymphadenopathy in the setting of COVID-19 vaccination.

Background Studies report hypercoagulability in coronavirus disease 2019 (COVID‐19), leading many institutions to escalate anticoagulation intensity for thrombosis prophylaxis. Objective To determine the bleeding risk with various intensities of anticoagulation in critically ill patients with COVID‐19 compared with other respiratory viral illnesses (ORVI). Patients/Methods This retrospective cohort study compared the incidence of major bleeding in patients admitted to an intensive care unit (ICU) within a single health system with COVID‐19 versus ORVI. In the COVID‐19 cohort, we assessed the effect of anticoagulation intensity received on ICU admission on bleeding risk. We performed a secondary analysis with anticoagulation intensity as a time‐varying covariate to reflect dose changes after ICU admission. Results Four hundred and forty‐three and 387 patients were included in the COVID‐19 and ORVI cohorts, respectively. The hazard ratio of major bleeding for the COVID‐19 cohort relative to the ORVI cohort was 1.26 (95% confidence interval [CI]: 0.86–1.86). In COVID‐19 patients, an inverse‐probability treatment weighted model found therapeutic‐intensity anticoagulation on ICU admission had an adjusted hazard ratio of bleeding of 1.55 (95% CI: 0.88–2.73) compared with standard prophylactic‐intensity anticoagulation. However, when anticoagulation was assessed as a time‐varying covariate and adjusted for other risk factors for bleeding, the adjusted hazard ratio for bleeding on therapeutic‐intensity anticoagulation compared with standard thromboprophylaxis was 2.59 (95% CI: 1.20–5.57). Conclusions Critically ill patients with COVID‐19 had a similar bleeding risk as ORVI patients. When accounting for changes in anticoagulation that occurred in COVID‐19 patients, therapeutic‐intensity anticoagulation was associated with a greater risk of major bleeding compared with standard thromboprophylaxis.

The COVID-19 pandemic has resulted in the increased use of cryopreserved grafts for allogeneic hematopoietic cell transplantation (HCT). However, information about the effect of cryopreservation on outcomes for patients receiving allogeneic donor grafts is limited. We evaluated outcomes of HCT recipients who received either fresh or cryopreserved allogeneic bone marrow (BM) or peripheral blood stem cell (PBSC) grafts reported to the Center for International Blood and Marrow Transplant Research. A total of 7397 patients were included in the analysis. Recipients of cryopreserved graft were divided into 3 cohorts based on graft source: HLA-matched related PBSC donors (n = 1051), matched unrelated PBSC donors (n = 678), and matched related or unrelated BM donors (n = 154). These patients were propensity score matched with 5514 patients who received fresh allografts. The primary endpoint was engraftment. Multivariate analyses showed no significant increased risk of delayed engraftment, relapse, nonrelapse mortality (NRM), or survival with cryopreservation of BM grafts. In contrast, cryopreservation of related donor PBSC grafts was associated with decreased platelet recovery (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.68 to 0.78; P < .001) and an increased risk of grade II-IV (HR, 1.27; 95% CI, 1.09 to 1.48; P = .002) and grade III-IV (HR, 1.48; 95% CI, 1.19 to 1.84; P < .001) acute graft-versus-host disease. Cryopreservation of unrelated PBSC grafts was associated with delayed engraftment of neutrophils (HR, 0.77; 95% CI, 0.71 to 0.84; P < .001) and platelets (HR, 0.61; 95% CI, 0.56 to 0.66; P < .001) as well as an increased risk of NRM (HR, 1.4; 95% CI, 1.18 to 1.66; P < .001) and relapse (HR, 1.32; 95% CI, 1.11 to 1.58; P = .002) and decreased progression-free survival (HR, 1.36; 95% CI, 1.20 to 1.55; P < .001) and overall survival (OS) (HR, 1.38; 95% CI, 1.22 to 1.58; P < .001). Reasons for cryopreservation were not routinely collected; however, in a subset of unrelated donor HCT recipients, the reason was typically a change in patient condition. Products cryopreserved for patient reasons were significantly associated with inferior OS in multivariate analysis (HR, 0.65; 95% CI, 0.44 to 0.96; P = .029). We conclude that cryopreservation is associated with slower engraftment of PBSC grafts, which may be associated with inferior transplantation outcomes in some patient populations. However, the small numbers in the cryopreserved BM cohort and the lack of information on the reason for cryopreservation in all patients suggests that these data should be interpreted with caution, particularly in the context of the risks associated with unexpected loss of a graft during the pandemic. Future analyses addressing outcomes when cryopreservation is universally applied are urgently required.

Background Recent publications have reported an association between increased renal cancer-specific mortality (CSM) and reduced renal function “below safety limits,” and advocated for partial nephrectomy (PN) even for potentially aggressive/complex tumors. We hypothesize that this association may be related to confounding factors rather than a consequence of functional differences. Objective To assess whether there is an independent association between preoperative estimated glomerular filtration rate (eGFR) or new baseline eGFR (NB-GFR) and CSM in patients undergoing PN or radical nephrectomy (RN). Design, setting, and participants A single-center retrospective review was performed. All clinically and pathologically confirmed T1-T3a/N0/M0 renal cancer patients undergoing PN/RN (1999–2008, n = 1605) with adequate functional/oncological data were included. Outcome measurements and statistical analysis The primary endpoint was CSM. Secondary endpoints were cancer recurrence (CR) and all-cause mortality (ACM). Cox regression analyses investigated endpoints and predictive factors. Results and limitations The median age was 60 yr and 64% of patients were male. Comorbidities included hypertension (60%), cardiovascular disease (19%), diabetes (21%), and chronic kidney disease (22%). PN was performed in 954 patients (59%). The median preoperative eGFR and NB-GFR were 80 and 60 ml/min/1.73 m2, respectively. Median tumor diameter was 3.6 cm (interquartile range [IQR] = 2.4, 5.5); 70% of tumors were clear cell and 40% were of high grade. Pathology revealed pT1–2/N0/M0 and pT3a/N0/M0 in 81% and 19%, respectively. The median follow-up among survivors was 11.5 yr (IQR = 4, 14). Cancer-specific survival, recurrence-free survival, and overall survival were 94%, 88%, and 73% at 10 yr, respectively. On multivariable analysis, increased age (hazard ratio [HR] = 1.03, p = 0.04), increased tumor size (HR = 1.24, p 0.1), while an increased preoperative eGFR was associated with reduced hazard of ACM (HR = 0.87, p Conclusions Our data do not support oncological protection of greater preservation of renal function and confirm that unfavorable oncological outcomes for localized RCC are mostly associated with aggressive tumor characteristics. Patient summary We did not find an association between greater preservation of renal function and oncological outcomes for kidney cancer.

Sinonasal papillomas are benign epithelial tumors of the sinonasal tract that are associated with a synchronous or metachronous sinonasal carcinoma in a subset of cases. Our group recently identified mutually exclusive EGFR mutations and human papillomavirus (HPV) infection in inverted sinonasal papillomas and frequent KRAS mutations in oncocytic sinonasal papillomas. We also demonstrated concordant mutational and HPV infection status in sinonasal papilloma-associated sinonasal carcinomas, confirming a clonal relationship between these tumors. Despite our emerging understanding of the oncogenic mechanisms driving formation of sinonasal papillomas, little is currently known about the molecular mechanisms of malignant progression to sinonasal carcinoma. In the present study, we utilized targeted next-generation DNA sequencing to characterize the molecular landscape of a large cohort of sinonasal papilloma-associated sinonasal carcinomas. As expected, EGFR or KRAS mutations were present in the vast majority of tumors. In addition, highly recurrent TP53 mutations, CDKN2A mutations, and/or CDKN2A copy-number losses were detected; overall, nearly all tumors (n = 28/29; 96.6%) harbored at least one TP53 or CDKN2A alteration. TERT copy-number gains also occurred frequently (27.6%); however, no TERT promoter mutations were identified. Other recurrent molecular alterations included NFE2L2 and PIK3CA mutations and SOX2, CCND1, MYC, FGFR1, and EGFR copy-number gains. Importantly, TP53 mutations and CDKN2A alterations were not detected in matched sinonasal papillomas, suggesting that these molecular events are associated with malignant transformation. Compared to aerodigestive tract squamous cell carcinomas from The Cancer Genome Atlas (TCGA) project, sinonasal papilloma-associated sinonasal carcinomas have a distinct molecular phenotype, including more frequent EGFR, KRAS, and CDKN2A mutations, TERT copy-number gains, and low-risk human papillomavirus (HPV) infection. These findings shed light on the molecular mechanisms of malignant progression of sinonasal papillomas and may have important diagnostic and therapeutic implications for patients with advanced sinonasal cancer.

INTRODUCTION Receiving a diagnosis of Alzheimer's disease or related dementias (ADRD) can be a pivotal and stressful period. We examined the risk of suicide in the first year after ADRD diagnosis relative to the general geriatric population. METHODS We identified a national cohort of Medicare fee-for-service beneficiaries aged ≥ 65 years with newly diagnosed ADRD (n = 2,667,987) linked to the National Death Index. RESULTS The suicide rate for the ADRD cohort was 26.42 per 100,000 person-years. The overall standardized mortality ratio (SMR) for suicide was 1.53 (95% confidence interval [CI] = 1.42, 1.65) with the highest risk among adults aged 65 to 74 years (SMR = 3.40, 95% CI = 2.94, 3.86) and the first 90 days after ADRD diagnosis. Rural residence and recent mental health, substance use, or chronic pain conditions were associated with increased suicide risk. DISCUSSION Results highlight the importance of suicide risk screening and support at the time of newly diagnosed dementia, particularly for patients aged

BACKGROUND Kidney transplant recipients are at increased risk of developing and dying from keratinocyte cancer. Risk factors for keratinocyte cancer death have not been previously described. METHODS In a cohort of kidney transplant recipients transplanted in Queensland 1995-2014, we identified keratinocyte cancer deaths by searching national transplant and state death registries to March 2020. Standardized keratinocyte cancer mortality rates and mortality ratios were calculated. We used a competing risks model to identify factors associated with keratinocyte cancer death and calculated relative risks (RRs) and 95% confidence intervals (CIs). RESULTS There were 562 deaths in 1866 kidney transplant recipients (62% males; 86% Caucasian) with 25 934 person-years of follow-up, of which 36 were due to squamous cell carcinoma (SCC) and 1 to basal cell carcinoma (BCC) with standardized mortality rates of 78 (95% CI 53-111) and 2 (95% CI 0.1-11) per 100,000 person-years respectively. The standardized mortality ratio for keratinocyte cancer was 23 (95% CI 23-24). Besides Caucasian ethnicity (associated with 100% of keratinocyte cancer deaths), male sex (RR 3.24 95% CI 1.26-8.33), and older age at transplantation (≥ 50 versus

Conventional sampling for pharmacokinetic clinical studies requires removal of large blood volumes from patients. This can result in a physiological/emotional burden for children. Microsampling to support pharmacokinetic clinical studies in pediatrics may reduce this burden. Parents/guardians and bedside nurses completed a questionnaire describing their perception of the use of microsampling compared to conventional sampling to collect blood samples, based on their child's participation or their own role within a paired-sample pharmacokinetic clinical study. Responses were based on a seven-point Likert scale and were analyzed using frequency distributions. Fifty-one parents/guardians and seven bedside nurses completed a questionnaire. Parents/guardians (96%) and bedside nurses (100%) indicated that microsampling was highly acceptable and recommended as a method for collecting blood samples for pediatric patients. Responding to a question about the child indicating pain during the blood sampling procedure, 61% of parent/guardians reported no pain in their children, 14% remained neutral, and 26% reported that their child indicated pain; 71% of the bedside nurses slightly agreed that the children indicated pain. This study strongly suggests that parents/guardians and bedside nurses prefer microsampling to conventional sampling to conduct pediatric pharmacokinetic clinical studies. Employing microsampling may support increased participation by children in these studies. Pharmacokinetic clinical studies require the withdrawal of blood samples at multiple times during a dosing interval. This can result in a physiological or emotional burden, particularly for neonates or pediatric patients. Microsampling offers an important opportunity for pharmacokinetic clinical studies in vulnerable patient populations, where smaller sample volumes can be collected. However, microsampling is not commonly used in clinical studies. Understanding the perceptions of parents/guardians and bedside nurses about microsampling may ascertain if this technique offers an improvement to conventional blood sample collection to perform pharmacokinetic clinical studies for pediatric patients.

Acute-care hospital reencounters (ACHEs)-encompassing emergency department visits, observation stays, and hospital readmissions-following COVID-19 hospitalization may exacerbate health care system strain and impair recovery from illness. We sought to characterize these reencounters and factors associated with reencounters. We identified the first consecutive 509 patients hospitalized for COVID-19 within an IL hospital network, and examined ACHEs, experienced within 30 days and 4 months of index hospitalization. We identified independent predictors of reencounter using binary logistic regression. Of 509 patients, 466 (91.6%) were discharged alive from index COVID-19 hospitalization. Within 30 days and 4 months, 12.4% and 21.5% of patients, respectively, experienced ACHEs. The median time to first ACHE was 24.2 (IQR 6.5, 55) days. COVID-19 symptom exacerbation was the leading reason for early ACHE (44.8%). Reencounters, both within 30 days and 4 months, were associated with a history of a neurological disorder before COVID-19 (OR 2.78 [95% CI 1.53, 5.03] and OR 2.75 [95% CI 1.67, 4.53], respectively). Older patients and those with diabetes mellitus, chronic obstructive pulmonary disease, or organ transplantation tended towards more frequent ACHEs. Steroid treatment during COVID-19 hospitalization demonstrated reduced odds of 30-day reencounter (OR 0.31 [95% CI 0.091, 0.79]). Forty-nine patients had repeat SARS-CoV-2 nasopharyngeal testing during a reencounter; twelve (24.5%) patients had positive reencounter tests and experienced more frequent reencounters than those testing negative. COVID-19 symptom exacerbation is a leading cause of early ACHE after COVID-19 hospitalization, and steroid use during index hospitalization may reduce early reencounters. Neurologic illness before COVID-19 predicts ACHEs.

We report a novel NIPBL-NACC1 gene fusion in a rare primary hepatic neoplasm previously described as the "cholangioblastic variant of intrahepatic cholangiocarcinoma." The 2 index cases were identified within our consultation files as morphologically distinctive primary hepatic neoplasms in a 24-year-old female and a 54-year-old male. The neoplasms each demonstrated varied architecture, including trabecular, organoid, microcystic/follicular, and infiltrative glandular patterns, and biphasic cytology with large, polygonal eosinophilic cells and smaller basophilic cells. The neoplasms had a distinctive immunoprofile characterized by diffuse labeling for inhibin, and patchy labeling for neuroendocrine markers (chromogranin and synaptophysin) and biliary marker cytokeratin 19. RNA sequencing of both cases demonstrated an identical fusion of NIBPL exon 8 to NACC1 exon 2, which was further confirmed by break-apart fluorescence in situ hybridization assay for each gene. Review of a tissue microarray including 123 cases originally diagnosed as well-differentiated neuroendocrine neoplasm at one of our hospitals resulted in identification of a third case with similar morphology and immunophenotype in a 52-year-old male, and break-apart fluorescence in situ hybridization probes confirmed rearrangement of both NIPBL and NACC1. Review of The Cancer Genome Atlas (TCGA) sequencing data and digital images from 36 intrahepatic cholangiocarcinomas (http://www.cbioportal.org) revealed one additional case with the same gene fusion and the same characteristic solid, trabecular, and follicular/microcystic architectures and biphasic cytology as seen in our genetically confirmed cases. The NIPBL-NACC1 fusion represents the third type of gene fusion identified in intrahepatic cholangiocarcinoma, and correlates with a distinctive morphology described herein.

Purpose While a growing number of research studies have reported the inter-observer variability in computed tomographic (CT) measurements, there are very few interventional studies performed. We aimed to assess whether a peer benchmarking intervention tool may have an influence on reducing inter-observer variability in CT measurements and identify possible barriers to the intervention. Materials and Methods In this retrospective study, 13 board-certified radiologists repeatedly reviewed 10 CT image sets of lung lesions and hepatic metastases during three non-contiguous time periods (T1, T2, T3). Each pre-selected case contained normal anatomy cephalad and caudal to the lesion of interest. Lesion size measurement under RECISTS 1.1 guidelines, choice of CT slice, and time spent on measurement were captured. Prior to their final measurements, the participants were exposed to the intervention designed to reduce the number of measurements deviating from the median. Chi-square test was performed to identify radiologist-dependent factors associated with the variability. Results The percent of deviating measurements during T1 and T2 were 20.0% and 23.1%, respectively. There was no statistically significant change in the number of deviating measurements upon the presentation of the intervention despite the decrease in percent from 23.1% to 17.7%. The identified barriers to the intervention include clinical disagreements among radiologists. Specifically, the inter-observer variability was associated with the controversy over the choice of CT image slice (p=0.045) and selection of start-point, axis, and end-point (p=0.011). Conclusion Clinical disagreements rather than random errors were barriers to reducing interobserver variability in CT measurement among experienced radiologists. Future interventions could aim to resolve the disagreement in an interactive approach.

Since the discovery of association of SMARCB1 mutations with malignant rhabdoid tumors and renal medullary carcinoma, mutations in genes of the SWI/SNF chromatin remodeling complex have been increasingly identified across a diverse spectrum of neoplasms. As a group, SWI/SNF complex subunit mutations are now recognized to be the second most frequent type of mutations across tumors. SMARCB1 mutations were originally reported in malignant rhabdoid tumors of the kidney and thought to be pathognomonic for this tumor. However, more broadly, recognition of typical rhabdoid cytomorphology and SMARCB1 mutations beyond rhabdoid tumors has changed our understanding of the pathobiology of these tumors. While mutations of SWI/SNF complex are diagnostic of rhabdoid tumors and renal medullary carcinoma, their clinical relevance extends to potential prognostic and predictive utility in other tumors as well. Beyond SMARCB1, the PBRM1 and ARID1A genes are the most frequently altered members of the SWI/SNF complex in genitourinary neoplasms, especially in clear cell renal cell carcinoma and urothelial carcinoma. In this review, we provide an overview of alterations in the SWI/SNF complex encountered in genitourinary neoplasms and discuss their increasing clinical importance.

BACKGROUND: Trimethylamine N-oxide (TMAO), a diet-derived, gut microbial-host cometabolite, has been linked to cardiometabolic diseases. However, the relations remain unclear between diet, TMAO, and cardiometabolic health in general populations from different regions and ethnicities. OBJECTIVES: To examine associations of circulating TMAO with dietary and cardiometabolic factors in a pooled analysis of 16 population-based studies from the United States, Europe, and Asia. METHODS: Included were 32,166 adults (16,269 white, 13,293 Asian, 1247 Hispanic/Latino, 1236 black, and 121 others) without cardiovascular disease, cancer, chronic kidney disease, or inflammatory bowel disease. Linear regression coefficients (β) were computed for standardized TMAO with harmonized variables. Study-specific results were combined by random-effects meta-analysis. A false discovery rate

Social media has been used increasingly in neurosurgery by individuals. We aimed to identify demographics and preferences of social media use, describe the scope of social media use, and characterize its utility.A systematic review was conducted using PubMed, Embase, and Scopus databases. Titles and abstracts from articles identified in the search were read and selected for full-text review. Studies meeting prespecified inclusion criteria were reviewed in full and analyzed for relevant data.Of 431 resultant articles, 29 were included. Patients and caregivers most commonly used Facebook and Twitter, whereas nearly 50% of neurosurgeons used LinkedIn and Doximity. Patient and caregiver users of social media tended to be35 years old. Content of posts varied from requesting/providing information (∼40%) to seeking emotional support/forming connections (∼30%). A total of 20.6% of videos were irrelevant to clinical neurosurgery. Factual accuracy of most videos was poor to inadequate. Social media use was associated with greater academic impact for neurosurgical departments and journals. Posts with photos and videos and weekend posts generated 1.2-2 times greater engagement.Patients and caregivers who use social media are typically younger than 35 years old and commonly use Facebook or Twitter. Neurosurgeons prefer Doximity and LinkedIn. Social media yields information regarding common symptoms and uncovers novel symptoms. Videos are poor-to-inadequate quality and often irrelevant to clinical neurosurgery. Optimizing social media use will augment the exchange of ideas regarding clinical practice and research and empower patients and caregivers.

In a large health system in the United States, investigators examined whether mortality, receipt of mechanical ventilation, and patient acuity changed over time among adult patients with COVID-19–related critical illness admitted to intensive care units., Visual Abstract. COVID-19–Related Critical Illness In a large health system in the United States, investigators examined whether mortality, receipt of mechanical ventilation, and patient acuity changed over time among adult patients with COVID-19–related critical illness admitted to intensive care units. Visual Abstract. COVID-19–Related Critical Illness In a large health system in the United States, investigators examined whether mortality, receipt of mechanical ventilation, and patient acuity changed over time among adult patients with COVID-19–related critical illness admitted to intensive care units., Background: The coronavirus disease 2019 (COVID-19) pandemic continues to surge in the United States and globally. Objective: To describe the epidemiology of COVID-19–related critical illness, including trends in outcomes and care delivery. Design: Single–health system, multihospital retrospective cohort study. Setting: 5 hospitals within the University of Pennsylvania Health System. Patients: Adults with COVID-19–related critical illness who were admitted to an intensive care unit (ICU) with acute respiratory failure or shock during the initial surge of the pandemic. Measurements: The primary exposure for outcomes and care delivery trend analyses was longitudinal time during the pandemic. The primary outcome was all-cause 28-day in-hospital mortality. Secondary outcomes were all-cause death at any time, receipt of mechanical ventilation (MV), and readmissions. Results: Among 468 patients with COVID-19–related critical illness, 319 (68.2%) were treated with MV and 121 (25.9%) with vasopressors. Outcomes were notable for an all-cause 28-day in-hospital mortality rate of 29.9%, a median ICU stay of 8 days (interquartile range [IQR], 3 to 17 days), a median hospital stay of 13 days (IQR, 7 to 25 days), and an all-cause 30-day readmission rate (among nonhospice survivors) of 10.8%. Mortality decreased over time, from 43.5% (95% CI, 31.3% to 53.8%) to 19.2% (CI, 11.6% to 26.7%) between the first and last 15-day periods in the core adjusted model, whereas patient acuity and other factors did not change. Limitation: Single–health system study; use of, or highly dynamic trends in, other clinical interventions were not evaluated, nor were complications. Conclusion: Among patients with COVID-19–related critical illness admitted to ICUs of a learning health system in the United States, mortality seemed to decrease over time despite stable patient characteristics. Further studies are necessary to confirm this result and to investigate causal mechanisms. Primary Funding Source: Agency for Healthcare Research and Quality.

Purpose:Preoperative estimation of new baseline glomerular filtration rate after partial nephrectomy or radical nephrectomy for renal cell carcinoma has important clinical implications. However, cu...

Androgen deprivation therapy (ADT), either by medical or surgical castration, is the backbone for standard treatment of locally advanced or metastatic prostate cancer, yet it is also associated with various metabolic and cardiovascular complications. Recent evidence have shown that obesity, insulin resistance, or metabolic disturbances can be associated with changes in the gut microbiome, while animal studies also show that castration is associated with changes in the gut microbiome. This study aims to investigate whether the fecal microbiota in prostate cancer patients who had undergone prostatectomy or ADT are different, and explore changes in phylogeny and pathways that may lead to side effects from ADT. A total of 86 prostate cancer patients (56 patients on ADT and 30 patients with prostatectomy) were recruited. The fecal microbiota was analyzed by the 16S rRNA gene for alpha- and beta-diversities by QIIME2, as well as the predicted metabolic pathways by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2. The alpha-diversity was significantly lower in the ADT group. The beta-diversity was significantly different between the groups, in which Ruminococcus gnavus and Bacteroides spp were having higher relative abundance in the ADT group, whereas Lachnospira and Roseburia were reduced. The Firmicutes-to-Bacteroidetes ratio is noted to be lower in the ADT group as well. The functional pathway prediction showed that the biosynthesis of lipopolysaccharide (endotoxin) and propanoate was enriched in the ADT as well as the energy cycle pathways. This study is limited by the cross-sectional design and the clinical heterogeneity. There is a significant difference in gut microbiome between prostate cancer patients on ADT and prostatectomy. We theorize that this difference may contribute to the development of metabolic complications from ADT. Further longitudinal studies are awaited.

Telerehabilitation technology has the potential to support the work of patients and clinicians by collecting and displaying patients' data to inform, motivate, and support decision-making. However, few studies have investigated data-driven practices in telerehabilitation. In this qualitative study, we conducted interviews and a focus group with the use of data visualization probes to investigate the experience of stroke survivors and healthcare providers with game-based telerehabilitation involving physical and occupational therapy. We find that \hlstudy participants saw potential value in the data to support their work. However, they experienced challenges when interpreting data to arrive at meaningful insights and actionable information. Further, patients' personal relationships with their goals and data stand in contrast with clinicians' more matter-of-fact perspectives. Informed by these results, we discuss implications for telerehabilitation technology design.