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Supplementary Figure 1 from Transforming Growth Factor β Receptor Type II Inactivation Promotes the Establishment and Progression of Colon Cancer

Deregulation of members of the transforming growth factor (TGF)-β signaling pathway occurs often in colon cancers and is believed to affect the formation of primary colon cancer. Mutational inactivation of TGFBR2 is the most common genetic event affecting the TGF-β signaling pathway and occurs in ∼20–30% of all colon cancers. By mating Fabpl4xat-132 Cre mice with Tgfbr2flx/flx mice, we have generated a mouse model that is null for Tgfbr2 in the colonic epithelium, and in this model system, we have assessed the effect of loss of TGF-β signaling in vivo on colon cancer formation induced by azoxymethane (AOM). We have observed a significant increase in the number of AOM-induced adenomas and adenocarcinomas in the Fabpl4xat-132 Cre Tgfbr2flx/flx mice compared with Tgfbr2flx/flx mice, which have intact TGF-β receptor type II (TGFBR2) in the colon epithelium, and we have found increased proliferation in the neoplasms occurring in the Fabpl4xat-132 Cre Tgfbr2flx/flx mice. These results implicate the loss of TGF-β-mediated growth inhibition as one of the in vivo mechanisms through which TGFBR2 inactivation contributes to colon cancer formation. Thus, we have demonstrated that loss of TGFBR2 in colon epithelial cells promotes the establishment and progression of AOM-induced colon neoplasms, providing evidence from an in vivo model system that TGFBR2 is a tumor suppressor gene in the colon.

Objective Transitioning into the early career physician workforce is a uniquely challenging period in a neonatologist's career. There are limited educational opportunities in fellowship regarding career progression, practice models, and benefits. Understanding these factors are key when searching for employment. This study evaluates the early career neonatologist (ECN) workforce and employment characteristics to improve identification of professional needs. Study Design An anonymous 59-question cross-sectional survey was distributed in July 2020 to members of the American Academy of Pediatrics Section on Neonatal Perinatal Medicine Trainees and Early Career Neonatologists (TECaN). The survey instrument was designed using SurveyMonkey and assessed search methods for identifying employers, employment contract details, and professional duties. Questions addressed clinical service time, level of acuity, protected research time, financial compensation, benefits, job search methods, and promotion requirements. Comparisons were drawn between respondents exclusively working in a university-based setting and respondents employed in nonuniversity locations. Responses were collected using SurveyMonkey and then extracted to a Microsoft Excel Workbook for analysis. Statistical analysis was performed using SAS version 9.4. Results Of 1,302 eligible members, 348 people responded (26.7%). Forty-six percent of respondents worked in a university setting and 54% worked in a nonuniversity setting. Using employment site as a discriminator, significant differences were noted in scheduling models. University-located respondents were more likely to work 2-week block schedules, fewer weekend/weeknight call, less clinical weeks per year, and more research/administrative weeks per year. Between university and nonuniversity located positions, benefits were largely comparable, while factors perceived as influential toward promotion varied depending on practice site. Conclusion This study provides ECNs with a contemporary workforce description vital to graduating TECaN seeking employment or renegotiating professional obligations. While benefits were largely similar based on practice site, promotion factors and scheduling models may vary depending on location. Key Points

OBJECTIVE To evaluate the efficacy and safety of tin mesoporphyrin (SnMP) in neonates with hyperbilirubinemia (HB) due to hemolysis. STUDY DESIGN This multicenter, placebo-controlled phase 2b study (NCT01887327) randomized newborns (35-42 weeks) with hemolysis started on phototherapy (PT) to placebo (Ctrl), SnMP 3.0 mg/kg, or SnMP 4.5 mg/kg given once IM within 30 min of initiation of PT. RESULTS In all, 91 patients were randomized (Ctrl: n = 30; 3 mg/kg SnMP: n = 30; 4.5 mg/kg SnMP: n = 31). At 48 h TSB significantly increased in Ctrl by 17.5% (95% CI 5.6-30.7; p = 0.004) and significantly decreased by -13% (95% CI -21.7 to -3.2; p = 0.013) in the 3.0 mg/kg and by -10.5% (95% CI -19.4 to -0.6; p = 0.041) in the 4.5 mg/kg group. Decreases in SnMP groups were significant (p

Trend in proportion in 2×K ordered tables is evaluated by assigning scores to ordered categories. Investigators often encounter 2×K ordered tables with an open-ended category. An open-ended category arises when category scores for the first K-1 categories are known or given a priori but the score for the last category is unknown. In such situations, an arbitrary score is often assigned to the openended (or the last) category before evaluating the trend. Thus two investigator analyzing the same data set may assign different scores and may arrive at different conclusions. In the spirit of preliminary data analysis it is shown through examples that there are situations where the conclusion is not affected by the choice of scores assigned to the open-ended category. The paper also explores situations where the conclusion may depend on the choice of a score for the openended category. In the former case, the usual trend analysis may be performed after assigning a score to the open-ended category. In the latter case, the trend may be evaluated after adjusting for the open-ended category as demonstrated in this paper. Alternately, the trend may be evaluated by Gautam's method which does not depend on a particular choice of a score.

We previously demonstrated significant gender and racial differences when self-Epworth Sleepiness Scale (ESS) and spouse-reported ESS were compared. In this study, we investigate whether gender specific self-ESS scores correlate with the objective measures of sleep quality. Seventy-nine patient–spouse pairs completed the ESS questionnaires after which patients underwent polysomnographic testing (PSG). The correlation between ESS results and the PSG-obtained measurements of sleep efficiency (SE), sleep arousal index (AI), and apnea hypopnea index (AHI) were evaluated by calculating Pearson’s and Spearman’s correlation coefficients. Differences within patient–spouse pairs were evaluated using Wilcoxon’s Rank Sum Test. Our results indicated significant difference between patient-reported and spouse-reported scores for all patient age/gender groups except for female patients over 60. Significant correlations were seen between female patient-reported ESS scores, but not their spouse-reported ESS scores, and all three objective measures of sleep. In contrast, there was no significant correlation between male patient, and spouse-reported ESS scores and SE, AI, and AHI. The answers of female patients to individual sleepiness scenarios on ESS strongly correlated with at least one of the PSG-obtained values. In male patients, only one sleepiness scenario correlated with AHI, and their spouse-reported answers to specific ESS questions correlated with patients’ SE. Self-reported ESS is an effective marker of sleep quality only in female patients. For male patients, self-reported and spouse-reported answers to the specific questions of the ESS rather than the total ESS score are better markers of sleep quality.

The role of multiparametric MRI (mp-MRI) for postproton radiation evaluation is unclear. In this pilot study, we characterize the mp-MRI features using the Prostate Imaging-Reporting and Data System (PI-RADS) for recurrent prostate cancer (PCa) following proton radiation therapy.After obtaining IRB approval, we identified 163 consecutive cases who underwent MRI-fusion prostate biopsy at our institution from November 2017 to May 2020. This study evaluated patients with prostate cancer (PCa) with biochemical recurrence following proton radiation. Patients were excluded if they had grossly metastatic disease, metal fragments, implanted devices, or with surgically removed prostates. The mpMRI studies were reviewed in depth and scored by 2 fellowship-trained radiologists. Following MRI-fusion biopsy of lesions of interest (LOI), slides were read by fellowship-trained pathologists.We found 14 patients with 16 lesions who met the study inclusion criteria. The median age was 69 years (range 57-79) and median time to biochemical recurrence was 7.3 years (range 3-13). On post-treatment imaging, decreases in prostate size and diffusely decreased T2 signal intensity were observed, making the use of apparent diffusion coefficient (ADC) and early enhancement at dynamic contrast enhanced (DCE) imaging often necessary for diagnosis of disease recurrence. We identified a total of 16 lesions with PIRADS scores of 3 or higher. Of these lesions, there were 5 PIRADS 3 lesions (4/5 (80%) without prostate cancer), 7 PIRADS 4-5 lesions (6 (86%) had high risk Pca), and 4 lesions with unassigned PIRADS scores (100% had high risk cancers). Among the MRI variables, diffusion weighted imaging (DWI) heterogeneity had the strongest association with recurrence of PCa (P0.001).Results of our pilot study showed that the PIRADS scoring system in the postproton radiation therapy setting has some correlations with prostate cancer recurrence; However, the clinical value of these findings are unclear. While definitive PIRADS categorization of lesions demonstrated expected frequency of cancer consistent with the scoring system, all unassigned lesions also harbored malignancy suggesting a cautious approach to PIRADS scoring system in postproton radiation setting. The findings from this study may be validated using a larger cohort.

This study seeks to identify patient socioeconomic factors that may be associated with no-shows to our academic urology clinics. This was a retrospective analysis of patient attendance to appointments scheduled at the main urology clinics of our academic center between April 2018 and April 2019. Attendance to scheduled appointments was computed and analyzed with respect to patients’ demographics and socioeconomic status, along with clinic site, type of provider scheduled with, and reason for visit. Chi-square test and simple and multiple logistic regression were performed in order to determine the relationship between patient no-show rates and the variables for appointment characteristics. The cohort of patients at highest risk for no-show was associated with those who were uninsured (OR = 30.00, 95% CI: 23.73-–7.92; p

Background: Primary adenoid cystic carcinoma (ACC) is the second most common primary tracheal neoplasms but the data for optimal treatment plan is limited. This study is an update of our institutional experience treating primary ACC of the trachea with neutron radiotherapy.

To examine how socioeconomic status (SES) and race affect parents' initial response (IR) to their child's mental illness (MI) including 1. Parental confidant(s); 2. Lag time in professional help-seeking; and 3. Referral source. 70 parents of patients new to a Child Psychiatry clinic completed a survey to assess their IR to their child's MI. SES was determined using the United States Census Bureau median income by zip codes. Summary statistics are frequencies and percentages for categorical data, and medians and quartiles for continuous data. Twenty-five percent of parents reported low SES and 31% Non-Caucasian Children (NCC). Confidants of Caucasian and NCC were Pediatrician (77% vs 50%, p = 0.03), and family (73% vs 32%, p = 0.002). Comparing help-seeking Lag Times 66% reported a delay of 1 year or more (p = 0.040). Overall Pediatricians were the leading confidant. Lag times were one year or more with stronger trends in NCC.

The purpose of this randomized controlled clinical trial was to determine whether an A1C value obtained at home by participants followed by a phone discussion of the result with a clinician would lead to 1) a more rapid and significant decrease in A1C, 2) more effective advancement of diabetes treatment, and 3) improvement in diabetes self-care behaviors. The study included 307 participants with type 2 diabetes, most of whom were of Latino origin. All study participants experienced a statistically significant reduction in mean A1C (control subjects −0.3%, P = 0.04; intervention subjects −0.5%, P = 0.0002), but there was a statistically significant difference in the number of people who achieved a reduction of ≥0.5% by 6 months, favoring the intervention (33.6 vs. 46.7%, P = 0.05).

Background: Overdose deaths involving opioids, heroin, and fentanyl-class drugs have dramatically increased in the United States in the last decade. In response to the epidemic, the City of Jacksonville (Florida) and local providers came together and developed a plan to reduce repeat overdoses and deaths called Project Save Lives (PSL). PSL utilized Certified Recovery Peer Specialists (CRPS) to engage overdose victims immediately following opioid overdose reversal and offered medication-assisted treatment, recovery support, overdose prevention services, and transportation to detox/treatment services all initiated within the Emergency Department (ED).

Clostridioides difficile is the most common cause of healthcare-associated infection and gastroenteritis-associated death in the USA. Adherence to guideline recommendations for treatment of severe C. difficile infection (CDI) is associated with improved clinical success and reduced mortality. The purpose of this study was to determine whether implementation of a pharmacist-led antimicrobial stewardship program (ASP) CDI initiative improved adherence to CDI treatment guidelines and clinical outcomes. This was a single-center, retrospective, quasi-experimental study evaluating patients with CDI before and after implementation of an ASP initiative involving prospective audit and feedback in which guideline-driven treatment recommendations were communicated to treatment teams and documented in the electronic health record via pharmacy progress notes for all patients diagnosed with CDI. The primary endpoint was the proportion of patients treated with guideline adherent definitive regimens within 72 hours of CDI diagnosis. Secondary objectives were to evaluate the impact on clinical outcomes, including length of stay (LOS), infection-related LOS, 30-day readmission rates, and all-cause, in-hospital mortality. A total of 233 patients were evaluated. The proportion of patients on guideline adherent definitive CDI treatment regimen within 72 hours of diagnosis was significantly higher in the post-interventional group (pre: 42% vs post: 58%, p=0.02). No differences were observed in clinical outcomes or proportions of patients receiving laxatives, promotility agents, or proton pump inhibitors within 72 hours of diagnosis. Our findings demonstrate that a pharmacist-led stewardship initiative improved adherence to evidence-based practice guidelines for CDI treatment.

Background Communication gaps in health care systems occur because of different care priorities of health care professionals. Such gaps contribute to errors, a significant cause of death in the United States. Method Framed by Ericsson's Expertise Theory, 20 teams of interprofessional health science students rotated through four scenarios with built-in medication errors after exposure to TeamSTEPPS® Essentials skills. Results Huddles improved in size and duration between rounds one and four. Huddle duration was inversely associated with care delays and patient harm. Attitudes toward teamwork improved significantly. Conclusions Multistation simulations facilitate deliberate practice of skills, enabling student improvement over time in critical competencies.

Background Venous invasion (VI) is not frequently evaluated on routine histologic examination of head and neck squamous cell carcinoma (HNSCC), and the prognostic significance is largely unknown. Studies have shown that extramural venous invasion is an adverse prognostic factor in colorectal carcinoma. To our knowledge, this is the first study evaluating the prognostic significance of venous invasion in node-negative (without clinical or pathologic evidence of lymph node involvement) HNSCC, utilizing the elastic stain. Methods A total of 105 consecutive lymph node-negative (N0) HNSCC were evaluated for the presence of venous channel invasion by tumor utilizing the elastin stain. Clinical, demographic, and follow-up data were recorded. Results Of 37 patients with venous invasion, 19% had loco-regional recurrence, as opposed to 12% of those without. Univariate analysis revealed statistically significant decreased recurrence-free survival in the presence of venous invasion (log-rank [Mantel-Cox] test P-value .025). Conclusion Identification of VI is greatly aided by elastic stain. In patients with node-negative HNSCC, presence of VI resulted in decreased recurrence-free survival on univariate analysis. The impact of VI as a prognostic marker should be further evaluated.

Studies directly comparing the different combination therapies offered to men with metastatic castration sensitive prostate cancer (mCSPC), are not available yet. This study was designed using the network meta-analysis (NMA) framework to provide a comparison of the different available options for the treatment of men with mCSPC.A systematic search was performed and the prospective randomized controlled trials reporting the overall survival (OS) or failure-free survival (FFS) were selected for review. A total of 14 studies were included in the NMA.The addition of abiraterone, apalutamide, docetaxel, and docetaxel with zoledronic acid to the androgen deprivation therapy (ADT) demonstrated a significant improvement in the OS. In indirect comparison, abiraterone had a higher impact on the OS as compared to docetaxel (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.0-1.46) and docetaxel with zoledronic acid (HR: 1.31, 95% CI: 1.05-1.63) but not apalutamide. Furthermore, apalutamide was not different than docetaxel or docetaxel with zoledronic acid. There was a significant improvement in the FFS with the combination of abiraterone, apalutamide, docetaxel (HR: 0.61, 95% CI: 0.46-0.81), docetaxel with zoledronic acid (HR: 0.62, 95% CI: 0.43-0.9), and enzalutamide (HR: 0.39, 95% CI: 0.25-0.61) as compared to the ADT alone. Similar to the indirect comparison of OS, abiraterone outperformed docetaxel (HR: 1.66, 95% CI: 1.12-2.47), docetaxel with zoledronic acid (HR: 1.69, 95% CI: 1.06-2.68), and enzalutamide (HR: 1.06, 95% CI: 0.63-1.80), but not apalutamide in terms of impact on the FFS.Overall, abiraterone demonstrated better OS and FFS outcomes as compared to all the other combination strategies in this NMA.

Low-grade prostate cancer has low mortality rates at 10 years; however, it is unclear if the response is sustained for up to 25 years of follow-up.Using Surveillance, Epidemiology, and End Results database, the overall and cancer-specific mortality rates were compared among men ≤ 55 years of age diagnosed with low-grade prostate cancer that either had radical prostatectomy, radiotherapy, or no known treatment.Of the 62,772 men diagnosed with low-grade prostate cancer between 1975 and 2016, about 60%, 20% and 20% of men underwent radical prostatectomy, radiotherapy, and no known treatment, respectively. At a median follow-up of 10 years, almost 2% and 7% of men died of prostate cancer and other causes, respectively. The overall mortality was significantly better in radical prostatectomy group compared to no known treatment group (HR 1.99, CI 1.84-2.15, P value 0.001), but not between the radiotherapy and no known treatment groups. Moreover, the overall and cancer-specific mortality rates in the radiotherapy group were almost two and three times compared to the radical prostatectomy group, respectively (HR 2.15, CI 2.01-2.29, P value 0.001 for overall mortality and HR 2.87, CI 2.5-3.29, P value 0.001 for cancer-specific mortality).The study confirms low mortality rates in men diagnosed with low-grade prostate cancer for over 25 years' follow-up. While radical prostatectomy improves survival significantly compared to no known treatment, radiotherapy is associated with an increase in overall and cancer-specific mortality, which may be related to long-term toxicities.

To evaluate the impact of desmopressin acetate (DDAVP) on poor outcomes, hematoma expansion, and adverse events in patients diagnosed with a non-traumatic, antiplatelet-associated intracranial hemorrhage (ICH).This was a multicenter, retrospective, propensity-matched cohort study comparing DDAVP to control in patients diagnosed with a non-traumatic ICH previously on antiplatelet therapy. Notable exclusion criteria included admission to trauma service, subarachnoid hemorrhages, confounding coagulopathic factors, and hematoma evacuation. Poor outcome, defined as discharge to hospice or in-patient mortality, was the primary outcome. Secondary outcomes included intracranial hematoma expansion and occurrence of adverse events, which included hyponatremia and thromboembolic events.A total of 49 patients receiving DDAVP were compared to 107 controls in the unmatched cohort. Thirty-seven patients treated with DDAVP and 55 controls were included in the propensity-matched analysis, which was adjusted for age, ethnicity, history of diabetes, receipt of platelet transfusion, and thromboembolism prophylaxis. Poor outcome (16.2% DDAVP vs 29% control, p = 0.13), rates of hematoma expansion (11.8% DDAVP vs 11.1% control, p = 0.99), and adverse events (21.6% DDAVP vs 20% control, p = 0.99) were statistically similar between the matched groups.DDAVP administration in patients with spontaneous antiplatelet-associated ICH was not associated with a reduction in poor outcomes, hematoma expansion, or an increase in adverse events. Use of DDAVP in this patient population appears to be safe. Larger prospective studies are warranted to evaluate DDAVP utility in this patient population.

Child maltreatment is an important public health problem with serious consequences. Even in the face of increased research and enhanced public awareness over the last decade, the rate of child fatalities due to reported child maltreatment has increased.This study describes pediatric emergency medicine (PEM) physicians' knowledge, training, confidence, and barriers in recognition and reporting suspected child maltreatment.A nationally representative sample of PEM physician members of Pediatric Emergency Medicine Collaborative Research Committee (PEM CRC) participated.A cross-sectional 36-item survey study of PEM physicians with content domains including provider knowledge, preparedness, confidence, and barriers to identifying and reporting child maltreatment was conducted and distributed.113 of 486 members completed the survey. Confidence with recognizing and reporting child abuse (95%) was greater than in child neglect (88%). Knowledge in child maltreatment recognition and reporting was significantly correlated with confidence in reporting and recognition (p 0.001). There was a significant relationship between knowledge and confidence for respondents from states with training in child maltreatment recognition and reporting requirement as a condition of licensure and re-licensure compared to states without the requirement (p 0.01). Qualitative responses revealed insightful themes to improve child maltreatment training, recognition and reporting.Our national survey study demonstrates that PEM-trained physicians have high confidence and knowledge with the management of child maltreatment, and that inclusion of mandated child maltreatment training in residency/fellowship and mandated training for medical licensure in all states could improve child maltreatment recognition and reporting.

The usual location of thoracic blunt traumatic aortic injury (BTAI) is just distal to the left subclavian artery; however, injuries can also be found in other locations in the descending thoracic aorta (DTA).This is a single-institution, retrospective study, using 74 consecutive BTAI in the DTA. The patients were separated into two groups based on the location of the injury. The proximal group included injuries within 5 cm of the left subclavian artery, whereas the distal group included injuries in the rest of the DTA. A total of 27 factors were compared.Between 2010 and July 2017, we identified 14 of 74 patients (19%) with BTAI in the distal zone. Females were 9 of the 14 (64%) in the distal zone group, whereas females were 16 of 60 (27%) in the proximal zone group (P .012). Thoracic spine fractures occurred in 7 of the 14 patients (50%) with injuries at the distal zone, whereas they occurred in 12 of the 60 patients (20%) in the proximal zone group (P .038). Eleven of the 14 distal zone injuries (79%) were grade 1 or 2 compared with 15 of 60 injuries (25%) at the proximal zone (P = .016). Only 2 of the 14 injuries (14%) in the distal zone required an endovascular repair as opposed to 39 of 60 (65%) in the proximal zone (P .001). The mean hospital duration of stay in patients with BTAI at the distal zone was 8.5 days compared with 20.3 days for patients in the proximal zone group (P .004). Mortality occurred in 5 of 14 patients (36%) in the distal zone group compared with 5 of 60 patients (8%) in the proximal zone group (P = .017). The odds of mortality from an injury in the distal zone were almost 6-fold greater than the odds of mortality from an injury in the proximal zone (odds ratio, 5.9; 95% confidence interval, 1.2-31.8). No mortalities were related to the BTAI itself. The association of location with mortality remained significant even after adjusting for other significant factors like Injury Severity Score and patient age. Patients who died from injuries in the distal zone had a shorter duration of stay (5 days vs 20 days; P = .0002).BTAI in the distal zone of DTA are associated with unique characteristics. They are (1) more frequently associated with thoracic spine fractures, (2) more common in women, (3) tend to be lower grade, (4) less likely to require intervention, and (5) seem to have a higher mortality owing to other associated traumatic injuries.

This systematic review aims to investigate spinal cord glioblastoma (scGBM) and correlations between patient traits and survival outcome, as well as differences in cohorts administered temozolomide or total resections, through an analysis of published cases reported up to October 2016.We obtained patient data by querying PubMed and Google Scholar with predetermined search terms and inclusion criteria that enabled the identification of relevant case reports. Survival was compared using Kaplan-Meier curves and log-rank analyses.Of 153 patients with scGBM identified through a literature search, 135 met the predetermined search and inclusion criteria. Median overall survival (OS) for the resulting cohort was 12 (95% CI, 10-14) months. The female sex was found to significantly predict worse outcomes, and a sizable number of patients with long-term disease were found to have afflictions of the thoracic spinal cord. Neither the pediatric, temozolomide nor total resection subgroups had significantly improved survival characteristics, by log-rank analysis, relative to counterparts.These data elucidate the characteristics of patients with scGBM. For more sophisticated and in-depth analyses in the future, it is imperative that time-of-treatment information is recorded in future case reports. In addition, all case reports should be made available to prevent publication bias.

To evaluate the efficacy and safety of tin mesoporphyrin (SnMP) in neonates with hyperbilirubinemia (HB) due to hemolysis.This multicenter, placebo-controlled phase 2b study (NCT01887327) randomized newborns (35-42 weeks) with hemolysis started on phototherapy (PT) to placebo (Ctrl), SnMP 3.0 mg/kg, or SnMP 4.5 mg/kg given once IM within 30 min of initiation of PT.In all, 91 patients were randomized (Ctrl: n = 30; 3 mg/kg SnMP: n = 30; 4.5 mg/kg SnMP: n = 31). At 48 h TSB significantly increased in Ctrl by 17.5% (95% CI 5.6-30.7; p = 0.004) and significantly decreased by -13% (95% CI -21.7 to -3.2; p = 0.013) in the 3.0 mg/kg and by -10.5% (95% CI -19.4 to -0.6; p = 0.041) in the 4.5 mg/kg group. Decreases in SnMP groups were significant (p 0.0001) vs Ctrl.SnMP with PT significantly reduced TSB by 48 h. SnMP may be useful as a treatment for HB in neonates with hemolysis.

The COVID-19 pandemic disproportionately affects females in the home and workplace. This study aimed to acquire information regarding the gender-specific effects of the COVID-19 lockdown on aspects of professional and personal lives of a subset of pediatric cardiologists. We sent an online multiple-choice survey to a listserv of Pediatric Cardiologists. Data collected included demographics, dependent care details, work hours, leave from work, salary cut, childcare hours before and after the COVID-19 peak lockdown/stay at home mandate and partner involvement. Two hundred forty-two pediatric cardiologists with dependent care responsibilities responded (response rate of 20.2%). A significantly higher proportion of females reported a salary cut (29.1% of females vs 17.6% of males, p = 0.04) and scaled back or discontinued work (14% vs 5.3%; p = 0.03). Prior to the COVID-19 lockdown phase, females provided more hours of dependent care. Females also reported a significantly greater increase in childcare hours overall per week (45 hours post/30 hours pre vs 30 hours post/20 hours pre for men; p0.001). Male cardiologists were much more likely to have partners who reduced work hours (67% vs 28%; p0.001) and reported that their partners took a salary cut compared with partners of female cardiologists (51% vs 22%; p0.001). In conclusion, gender disparity in caregiver responsibilities existed among highly skilled pediatric cardiologists even before the COVID-19 pandemic. The pandemic has disproportionately affected female pediatric cardiologists with respect to dependent care responsibilities, time at work, and financial compensation.

Epidemiological studies have reported strong association between sleep loss and hypertension with unknown mechanisms. This study investigated macrovascular and microcirculation changes and inflammatory markers during repetitive sleep restriction. Sex differences were also explored. Forty-five participants completed a 22-day in-hospital protocol. Participants were assigned to, (1) eight-hour sleep per night (control), or (2) sleep restriction (SR) condition: participants slept from 0300 to 0700 h for three nights followed by a recovery night of 8-h sleep, repeated four times. Macrocirculation assessed by flow mediated dilation (FMD) and microcirculation reactivity tests were performed at baseline, last day of each experimental block and during recovery at the end. Cell adhesion molecules and inflammatory marker levels were measured in blood samples. No duration of deprivation (SR block) by condition interaction effects were found for FMD, microcirculation, norepinephrine, cell adhesion molecules, IL-6 or IL-8. However, when men and women were analyzed separately, there was a statistical trend (p = 0.08) for increased IL-6 across SR blocks in women, but not in men. Interestingly, men showed a significant progressive (dose dependent) increase in skin vasodilatation (p = 0.02). A novel and unexpected finding was that during the recovery period, men that had been exposed to repeated SR blocks had elevated IL-8 and decreased norepinephrine. Macrocirculation, microcirculation, cell adhesion molecules, and markers of inflammation appeared to be resistant to this model of short-term repetitive exposures to the blocks of shortened sleep in healthy sleepers. However, men and women responded differently, with women showing mild inflammatory response and men showing more vascular system sensitivity to the repetitive SR.

Despite the reduced caloric content of artificially sweetened beverages (ASBs) relative to those sweetened with sucrose, consumption of ASBs fail to consistently decrease the risk of obesity and associated diseases. This failure may be due to the inability of ASBs to effectively reduce appetite and hence overall caloric intake. A variety of non-nutritive sweeteners (NNS), however, remain to be screened for effectiveness in promoting satiety and reducing calorie consumption. Erythritol is well-tolerated, low-calorie sugar alcohol widely used as a sugar substitute. It is unique among NNS due to its low sweetness index relative to glucose, meaning that it is typically served at much higher concentrations than other common NNS. Animal and human studies have noted correlations between osmolarity, satiety, and levels of satiety hormones, independent of the effects of sweetness or nutritive value. We hypothesized that consumption of a beverage sweetened with erythritol to the sweetness and osmolarity of a common soft drink will improve self-reported satiety and more strongly affect the magnitude of changes in the hormone ghrelin than would an iso sweet beverage sweetened only with aspartame, a sweetener with a high sweetness index relative to glucose. Using a randomized double-blind crossover trial, we found that serum ghrelin was significantly decreased after consumption of an erythritol-sweetened beverage compared to aspartame. Likewise, consumption of the erythritol-sweetened beverage increased various measures of satiety in volunteers. Knowledge gained from this project demonstrates that high-osmolarity NNS may be useful in formulating ASBs that are satiating and low in calories.

Objective: This study was designed to provide an indirect comparison of the urinary and sexual domain outcomes and complications after newer minimally invasive surgical therapy (MIST) of Aquablatio...

Objective The objective of this study was to determine predictive factors for pain-related emergency department returns in middle-aged and older adults. Design, Setting, and Subjects. This was a subanalysis of patients > 55 years of age enrolled in a prospective observational study of adult patients presenting within 30 days of an index visit to a large, urban, academic center. Methods Demographic and clinical data were collected and compared to determine significant differences between patients who returned for pain and those who did not. Multiple logistic regressions were used to determine significant predictive variables for return visits. Results The majority of the 130 enrolled patients > 55 years of age returned for pain (57%), were African American (78%), were younger (55–64 years old, 67%), had a high emergency department acuity level (level 1 or 2) at their index visit (56%), had low health literacy (Rapid Estimate of Adult Literacy in Medicine [REALM] score, 62%), lived in an area of extreme deprivation (69%), and were admitted (61%) during their index visit. Age (odds ratio [OR] = 0.9, 95% CI = 0.8–0.9, P = 0.047), health literacy (REALM scores; OR = 3.1, 95% CI = 1.3–7.5, P = 0.011), and index visit pain scores (OR = 1.1, 95% CI = 1.0–1.2, P = 0.004) were predictive of emergency department returns for pain in middle-aged and older adults. Conclusions The likelihood of emergency department return visits for pain in middle-aged and older adults decreased with older age, increased with higher health literacy (REALM scores), and increased with increase in pain scores.

To determine the risk factors associated with loss of functional independence after obliterative procedures for pelvic organ prolapse (POP). The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database was used to collect data on women who underwent obliterative vaginal procedures from 2011 to 2016, using current procedural terminology (CPT) codes for LeFort colpocleisis (57120) and vaginectomy (57110). The criterion for loss of functional independence was a transition from a functionally independent status to a dependent status (discharge to a post-care facility) or death within the 30-day postoperative period. Multivariate regression analysis was utilized to determine factors associated with loss of functional independence. A total of 1847 women were included in the analysis. A loss of functional independence was noted in 50 of the 1847 women (2.6%). The women who suffered loss of functional independence were older than those who were independent postoperatively (mean age 79.3 years, SD 7.47 vs. 76.7 years, SD 8.1, respectively). On multiple logistic regression analysis, age ≥ 80 years (OR 2.8, 95% CI 1.4–5.5), American Society of Anesthesiologists (ASA) classification ≥ 3 (OR 2.3, CI 1.1–4.7) and length of stay ≥ 5 days (OR 15.2, 95% CI 6.2–37.1) remained significantly associated with an increased risk of loss of functional independence. Age ≥ 80 years, ASA classification ≥ 3 and longer length of stay are associated with an increased risk of loss of functional independence after an obliterative procedure for pelvic organ prolapse. Consideration of these factors during the preoperative decision-making process may help improve outcomes in this cohort.

Introduction Randomized clinical trials have shown combination therapy to be superior in progression-free survival (PFS) rates when compared with sunitinib alone. However, there have been no direct comparisons among the combination strategies making it unclear as to which may be the preferred option. We performed a network meta-analysis of the combination therapy (immune checkpoint inhibitor plus axitinib or bevacizumab) used in metastatic renal cell carcinoma (mRCC) and provided a rank order preference based on PFS, and adverse events (AEs). Materials and methods A systematic search on the treatment of mRCC using combination therapy till July 2019 was done. Studies reporting on combination therapies with immune checkpoint inhibitor plus axitinib or bevacizumab for mRCC were selected. Frequentist method was used for rank order generation. Results A total of 3 studies consisting of 2672 patients were selected. All combination therapies demonstrated improved PFS when compared with sunitinib alone. The rank order for PFS showed combination of pembrolizumab plus axitinib had the highest probability of favorability followed by avelumab plus axitinib and atezolizumab plus bevacizumab (surface under the cumulative ranking 0.9, 0.7, and 0.4, respectively). For AEs, pembrolizumab plus axitinib had the least AEs ≥grade 3, followed by avelumab plus axitinib and atezolizumab plus bevacizumab (surface under the cumulative ranking 0, 0.5, 1.0). Conclusions This network meta-analysis demonstrates that combination of pembrolizumab plus axitinib may be the preferred option based on efficacy and side effect profile compared with avelumab plus axitinib or atezolizumab plus bevacizumab. However, all the 3 combination strategies were superior to sunitinib alone in improving PFS in patients with mRCC.

INTRODUCTION AND OBJECTIVE:Recently, the Phase-III trials with second generation androgen receptor antagonists (Apalutamide, Enzalutamide and Darolutamide) have shown similar efficacy, leaving clin...

INTRODUCTION AND OBJECTIVE:Spinal cord injury (SCI) is one of the most devastating injuries not only to the patient but also to the family and society. Genitourinary (GU) complications are among th...

INTRODUCTION AND OBJECTIVE:The natural history of prostate cancer (PC) in men of > 70 years of age is not well defined. Although the current recommendation for PC screening is limited to 70 years o...

INTRODUCTION AND OBJECTIVE:Patient no-show to scheduled outpatient ambulatory clinic appointments adversely impacts healthcare costs and the quality of patient care. In this study, we seek to ident...

INTRODUCTION AND OBJECTIVE:The combination of immune checkpoint inhibitors and antiangiogenics have emerged as a new treatment modality for metastatic renal cell carcinoma (mRCC). Recent randomized...

Introduction: Studies using apalutamide, enzalutamide, or darolutamide have shown improved metastasis free survival (MFS) rates, leaving clinicians with a dilemma of choosing one over the other, for nonmetastatic castration recurrent prostate cancer (nmCRPC). We performed a network meta-analysis to provide an indirect comparison of oncologic outcomes and adverse events (AEs) of these medications. Material and Methods: We searched PubMed, MEDLINE, and SCOPUS databases, for studies reporting apalutamide, enzalutamide, or darolutamide until January 25, 2020. Results were input into an EndNote library, and data were extracted into a predefined template. Progression free survival (PFS) was defined as radiologic progression or death. Network meta-analysis was done using R and meta-analysis was performed with RevMan v. 5. Surface under the cumulative ranking (SUCRA) value was used to provide rank probabilities. Results: We found 3 studies reporting results for apalutamide, enzalutamide, and darolutamide. MFS was significantly lower in patients receiving darolutamide compared to both apalutamide (hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.55–0.97) and enzalutamide (HR: 0.71, 95% CI: 0.54–0.93). MFS was similar for enzalutamide and apalutamide (HR: 0.97, 95% CI: 0.73–1.28). In PFS, apalutamide showed a slightly higher rate compared to darolutamide (HR: 0.76, 95% CI: 0.59–0.99). There was no difference in overall survival (OS) between any of the medications. There was no statistically significant difference in AEs profile of the 3 medications. However, darolutamide had the highest SUCRA value and probability of being the most preferred medication based on AEs profile. Conclusion: Enzalutamide and apalutamide had similar and higher MFS rate in indirect comparison with darolutamide. In cases where AEs are concerning, darolutamide might be the preferred agent.

Background The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) calculator is a useful tool used by physicians to better inform patients on the surgical risk of postoperative complications. It makes use of the NSQIP database to derive the chance for several adverse outcomes to occur postoperatively given certain patient's factors. The aim of this study was to assess its applicability in a series of patients undergoing an Ivor Lewis esophagectomy. Methods Data from 100 consecutive patients who underwent an Ivor Lewis esophagectomy between September 2013 and November 2017 at our institution were reviewed. Each patient was assessed using the ACS NSQIP surgical risk calculator. Actual events in this group were compared with their particular NSQIP-assessed risk. Logistic regression models were used to compare surgical risk calculator estimates binary outcomes such as incidence of postoperative complications such as cardiac events, renal events, surgical site infection, and death. Mixed linear model was used for length of stay (LOS) duration versus observed LOS. C-statistic was for predictive accuracy each binary outcome and intraclass correlation was used for LOS. Results C-statistic values were higher than the cutoff (0.75) for surgical site infection and death. The ACS NSQIP risk calculator was poorly predictive of other reported outcomes by the calculator such as cardiac or renal complications. Corroboration between observed LOS and predicted LOS was weak (8 d versus 11 d, respectively, intraclass coefficient 0.04). Conclusions This study suggests that the risk calculator is useful for identifying risk of death or surgical site infection but poor at discriminating likelihood of other reported outcomes occurring, such as pneumonia, acute renal failure and cardiac complications for patients who underwent an Ivor Lewis esophagectomy. Estimations for procedure-specific complications for esophagectomy may need reevaluated.

Our specific, measurable, attainable, relevant, and time-limited (SMART) aim was to reduce the incidence of severe intracranial hemorrhage (ICH) among preterm infants born

New primary cancers can occur in patients with a previous cancer. Among the risk factors, therapies such as chemotherapy, radiotherapy, and hormonal therapy have been associated with the development of neoplasms. Second cancers most commonly develop 5–10 years after the initial tumor. We observe the implications of cancer-related therapy in the development of a new tumor. We looked at 602 patients who had their first cancer diagnosed in 2011 and calculated the number of different primary cancers between 2011 and 2016 for each patient. Twenty-four patients had a second cancer within 5 years from the first diagnosis and there were no patients with a third cancer. There was no statically significant difference in the rates of second cancers after exposure to chemotherapy, radiotherapy, hormonal therapy, or any combination of these (p=0.738). Of the second cancers reported after 2011, renal, uterine, cervical, and lung cancers were the most frequently reported. Additionally, there was no statically significant difference among the rates of second cancers in men versus women (p=0.467), as well as among whites versus blacks (p=0.318). We conclude that while new primaries can occur after one cancer, there was no increased risk after exposure to different cancer-related therapies. With increased focus on the primary disease, there is a higher likelihood of missing another primary lesion. This is important as the practical implications of managing multiple primaries are rarely discussed.

To cope up with the Big Data explosion, the Nth Order Binary Encoding (NOBE) algorithm with the Split-protocol has been proposed. In the earlier papers, the application Split-protocol for security, reliability, availability, HPC have been demonstrated and implemented encoding. This technology will significantly reduce the network traffic, improve the transmission rate and augment the capacity for data storage. In addition to data compression, improving the privacy and security is an inherent benefit of the proposed method. It is possible to encode the data recursively up to N times and use a unique combination of NOBE's parameters to generate encryption keys for additional security and privacy for data on the flight or at a station. This paper describes the design and a preliminary demonstration of (NOBE) algorithm, serving as a foundation for application implementers. It also reports the outcomes of computable studies concerning the performance of the underlying implementation.