The ENGAGE study: a 3-arm randomized hybrid type 1 effectiveness and implementation study of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic services in childhood cancer survivors.

BACKGROUND: Germline cancer genetic testing has become a standard evidence-based practice, with established risk reduction and screening guidelines for genetic carriers. Access to genetic services is limited in many places, which leaves many genetic carriers unidentified and at risk for late diagnosis of cancers and poor outcomes. This poses a problem for childhood cancer survivors, as this is a population with an increased risk for subsequent malignant neoplasms (SMN) due to cancer therapy or inherited cancer predisposition. The ENGaging and Activating cancer survivors in Genetic services (ENGAGE) study evaluates the effectiveness of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic testing in childhood cancer survivors compared to usual care options for genetic testing. METHODS: The ENGAGE study is a 3-arm randomized hybrid type 1 effectiveness and implementation study within the Childhood Cancer Survivor Study population which tests a clinical intervention while gathering information on its delivery during the effectiveness trial and its potential for future implementation among 360 participants. Participants are randomized into three arms. Those randomized to Arm A receive genetic services via videoconferencing, those in Arm B receive these services by phone, and those randomized to Arm C will receive usual care services. DISCUSSION: With many barriers to accessing genetic services, innovative delivery models are needed to address this gap and increase uptake of genetic services. The ENGAGE study evaluates the effectiveness of an adapted model of remote delivery of genetic services to increase the uptake of recommended genetic testing in childhood cancer survivors. This study assesses the uptake in remote genetic services and identify barriers to uptake to inform future recommendations and a theoretically-informed process evaluation which can inform modifications to enhance dissemination beyond this study population and to realize the benefits of precision medicine. TRIAL REGISTRATION: This protocol was registered at clinicaltrials.gov (NCT04455698) on July 2, 2020.

Eliminating children's tobacco smoke exposure: a pathway to bioverified abstinence among low-income maternal smokers in the Babies Living Safe and Smokefree (BLiSS) trial.

BACKGROUND: Identifying behavioral pathways to smoking cessation in high-risk populations, such as low-income maternal smokers, could reduce tobacco disparities. The previous "BLiSS" multilevel intervention trial demonstrated efficacy of the BLiSS intervention in facilitating low-income maternal smokers' bioverified abstinence. This present study examined four putative pathways measured at 3-month end of treatment (Time 2) that could account for the observed intervention effect on smoking abstinence through 12 months (Time 2 - Time 3). METHODS: Nutritionists in community clinics delivering safety net nutrition promotion programs across Philadelphia, Pennsylvania, USA, were trained by trial principal investigators to deliver a brief tobacco intervention informed by the American Academy of Pediatrics best practice guidelines ("Ask, Advise, Refer [AAR]"). After referral, 396 eligible participants were randomized to either a multimodal behavioral intervention (AAR + MBI) or a parallel attention control (AAR + control). Random effects regression analysis tested mediation. RESULTS: Elimination of children's tobacco smoke exposure (TSE) at Time 2 was the only significant mediator of longitudinal smoking abstinence through Time 3. AAR + MBI mothers were more likely to eliminate their children's TSE by Time 2 (OR = 2.11, 95%CI 1.30, 3.42), which was significantly associated with Time 3 abstinence (OR = 6.72, CI 2.28, 19.80). Modeling showed a significant total effect of AAR + MBI on abstinence (OR = 6.21, CI 1.86, 20.71), a direct effect of AAR + MBI on abstinence (OR = 4.80, CI 1.45, 15.94) and an indirect effect through TSE elimination (OR = 1.29, CI 1.06, 1.57). CONCLUSIONS: Integrating smoking cessation interventions with counseling prior to the quit attempt that is designed to facilitate adoption of smokefree home policies and efforts to eliminate children's TSE could enhance the likelihood of long-term abstinence in populations of smokers with elevated challenges quitting smoking.

Timing of Unplanned Reoperation After Lower Extremity Free Flap Reconstruction: What Are the Roles of Procedure Indication and Defect Etiology?

BACKGROUND: Advancements in lower extremity (LE) microsurgery have allowed for the expansion of indications for LE reconstructions. This project aims to better understand the temporal pattern and risk factors associated with LE free flap failure based on the clinical indication. MATERIALS AND METHODS: We analyzed all patients undergoing LE free flap reconstruction from the American College of Surgeons National Surgical Quality Improvement Program 2012-2019 prospectively collected data to determine rates and timing of reoperation. Free flaps were stratified by indication, type, and timing of reoperation. Weibull survival models were used to compare rates of takebacks among time intervals. Multivariable logistic regression was used to identify independent predictors for unplanned reoperation. RESULTS: Four hundred seven of LE free flaps were analyzed. There was a 14.5% rate (59/407) of unplanned reoperation within the first 30 postoperative days (PODs) after surgery. When stratified by the indication necessitating reoperation, patients with an underlying vascular indication had the highest rate of reoperation (40.9%). The reoperation rates were significantly different between indications (P < 0.05) The mean daily proportion of patients experiencing reoperation was highest during POD 0 to 2 (1.47% reoperations per day), which dropped significantly during POD 3 to 10 (0.55% per day) and again during POD 11 to 30 (0.28% per day, P < 0.05). African American race as well as malignant, prosthetic/implant, and wound/infectious indications were significant independent predictors for unplanned reoperation. CONCLUSIONS: Lower extremity reconstruction is an important reconstructive option for the coverage of a myriad of defects. Understanding the differences between postoperative reoperation timelines among indication subtypes is important for updated flap monitoring protocols, optimizing ERAS pathways, and beginning dangle protocols.

Significant Reduction in Length of Stay in Deep Inferior Epigastric Perforator Flap Breast Reconstruction With Implementation of Multimodal ERAS Protocol.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) implementation achieves earlier recovery, reduced hospital length of stay (LOS) and improved outcomes in patients undergoing deep inferior epigastric perforator (DIEP) free flaps. We sought to review our ERAS protocols and their impact on our patients' LOS compared with the literature. METHODS: This was a retrospective review of a single surgeon's experience from 2017 to 2021 of patients undergoing DIEP free-flap breast reconstruction with LOS as the primary outcome. Complication rates and patient demographics are described as secondary outcomes. RESULTS: One hundred twenty-one patients underwent DIEP free-flap breast reconstruction. After adapting ERAS protocols, there has been a 0.98 [SD, 0.17; confidence interval [CI], -1.3 to -0.64; P < 0.001) day decrease in length of stay comparing pre-ERAS to post-ERAS implementation. Length of stay has routinely decreased from an average discharge on day 4.17 (SD, 1.1; range, 3-8 days) in 2017 to discharge on day 2.91 (SD, 1.1; range, 1-5 days) in 2021. Seventy-five percent of patients in 2021 were hospitalized for 3 or fewer days compared with 75% of patients in 2017 hospitalized for 4 or more days. One patient experienced a flap failure. Our study supports successful discharge on postoperative days 2-3 compared with postoperative days 3-4 in the current literature. CONCLUSIONS: The implementation of our ERAS protocol for DIEP free-flap breast reconstruction has resulted in a shorter LOS compared with contemporary literature. The ERAS protocols can be efficiently adopted in microsurgical DIEP breast reconstruction to achieve a shorter LOS without jeopardizing patient outcomes.

The critical need to implement and utilize patient-reported measures of function in cancer care delivery.

The study by Smith et al. on the Patient-Reported Outcomes Measurement Information System (PROMIS) Cancer Function Brief 3D Profile shows that it can be used to measure how an individual functions and how his or her function changes during cancer treatments. This is important because most patients will experience a decline in function during cancer treatment and will struggle to fully participate in their life roles. Strong evidence demonstrates that rehabilitation improves function for individuals with cancer; rehabilitation is relatively underutilized. We suggest that using the PROMIS tool as a repeated measure throughout cancer treatment will help to identify those with functional decline who will benefit most from rehabilitation.

Multilevel Intervention for Low-Income Maternal Smokers in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

Objectives. To test the efficacy of Babies Living Safe and Smokefree (BLiSS), a multilevel intervention initiated in a citywide safety net health system to improve low-income maternal smokers' abstinence and reduce child tobacco smoke exposure. Methods. This randomized controlled trial in Philadelphia, Pennsylvania (2015-2020), recruited low-income maternal smokers who received a brief smoking intervention (Ask, Advise, Refer [AAR]) from nutrition professionals in the Special Supplemental Nutrition Program for Women, Infants, and Children before randomization to (1) a multilevel intervention (AAR + multimodal behavioral intervention [MBI]; n = 199) or (2) an attention control intervention (AAR + control; n = 197). Results. AAR + MBI mothers had significantly higher 12-month bioverified abstinence rates than did AAR + control mothers (odds ratio [OR] = 9.55; 95% confidence interval [CI] = 1.54, 59.30; P = .015). There were significant effects of time (b = -0.15; SE = 0.04; P < .001) and condition by time (b = -0.19; SE = 0.06; P < .001) on reported child exposure favoring AAR + MBI, but no group difference in child cotinine. Presence of other residential smokers was related to higher exposure. Higher baseline nicotine dependence was related to higher child exposure and lower abstinence likelihood at follow-up. Conclusions. The multilevel BLiSS intervention was acceptable and efficacious in a population that experiences elevated challenges with cessation. Public Health Implications. BLiSS is a translatable intervention model that can successfully improve efforts to address the persistent tobacco-related burdens in low-income communities. Trial Registration. Clinical Trials.gov identifier: NCT02602288. (Am J Public Health. 2022;112(3):472-481. https://doi.org/10.2105/AJPH.2021.306601).

Critical Importance of the First Postoperative Days After Head and Neck Free Flap Reconstruction: An Analysis of Timing of Reoperation Using the National Surgical Quality Improvement Program Database.

BACKGROUND: Head and neck free flaps remain associated with considerable rates of take-back and prolonged hospital length of stay. However, there have been no studies on a national level benchmarking the timeline and predictors of head and neck free flap take-back. METHODS: Patients undergoing head and neck free flap reconstruction from the American College of Surgeons National Surgical Quality Improvement Program 2012-2019 database were analyzed to determine the rates of take-back. Timing and rates of unplanned head and neck free flap take-backs were stratified by tissue type and postoperative day (POD) over the first month. Weibull survival models were used to compare rates of take-backs among time intervals. Multivariable logistic regression was used to identify the independent predictors of take-back. RESULTS: Three thousand nine hundred six head and neck free flaps were analyzed. The mean daily proportion of patients experiencing take-back during PODs 0 to 1 was 0.95%; this dropped significantly to a mean daily proportion of 0.54% during POD 2 (P < 0.01). In addition, there were significant drops in take-back when comparing POD 2 (0.54%) to POD 3 (0.26%) and also when comparing POD 4 (0.20%) with PODs 5 to 30 (0.032% per day) (P < 0.05). The soft tissue and osseous flap populations demonstrated a similar trend in unplanned take-back. CONCLUSION: This is the first national study to specifically analyze the timing of take-back in the head and neck reconstruction population. These data highlight the importance of flap monitoring during the first 5 PODs, with ERAS pathway optimization aiming for discharge by the end of the first postoperative week.

Data Quality of Automated Comorbidity Lists in Patients With Mental Health and Substance Use Disorders.

EHRs provide an opportunity to conduct research on underrepresented oncology populations with mental health and substance use disorders. However, a lack of data quality may introduce unintended bias into EHR data. The objective of this article is describe our analysis of data quality within automated comorbidity lists commonly found in EHRs. Investigators conducted a retrospective chart review of 395 oncology patients from a safety-net integrated healthcare system. Statistical analysis included κ coefficients and a condition logistic regression. Subjects were racially and ethnically diverse and predominantly used Medicaid insurance. Weak κ coefficients ( κ = 0.2-0.39, P < .01) were noted for drug and alcohol use disorders indicating deficiencies in comorbidity documentation within the automated comorbidity list. Further, conditional logistic regression analyses revealed deficiencies in comorbidity documentation in patients with drug use disorders (odds ratio, 11.03; 95% confidence interval, 2.71-44.9; P = .01) and psychoses (odds ratio, 0.04; confidence interval, 0.02-0.10; P < .01). Findings suggest deficiencies in automatic comorbidity lists as compared with a review of provider narrative notes when identifying comorbidities. As healthcare systems increasingly use EHR data in clinical studies and decision making, the quality of healthcare delivery and clinical research may be affected by discrepancies in the documentation of comorbidities.

Postoperative Complications Associated with the Choice of Reconstruction in Head and Neck Cancer: An Outcome Analysis of 4,712 Patients from the ACS-NSQIP Database.

BACKGROUND: Microsurgical free flaps have largely supplanted pedicled flaps as the gold standard for head and neck cancer reconstruction. However, incidence of postoperative complications after accounting for patient comorbidities based on choice of reconstruction has not been well-defined in the literature in recent years. METHODS: Patients undergoing head and neck reconstruction were identified in the 2011-2016 ACS-NSQIP (American College of Surgeons National Surgical Quality Improvement Program) database and stratified into groups by free flap, myocutaneous pedicled flap, and other reconstruction. Demographics were analyzed and covariates balanced using overlap propensity score-based weighting. Logistic regression was used for binary outcomes and Gamma generalized linear model was used for length of stay. RESULTS: A total of 4,712 patients met inclusion criteria out of which 1,297 patients (28%) underwent free flap, 208 patients (4%) pedicled flap, and 3,207 patients (68%) had other, or no reconstruction performed. After adjusting for patient and disease-specific factors, pedicled flap reconstruction was associated with a higher risk of deep vein thrombosis (odds ratio [OR] = 2.64, confidence interval [CI] 1.02-6.85, p = 0.045), sepsis (OR = 2.95, CI 1.52-5.71, p = 0.001), and infection (OR = 2.03, CI 1.39-2.96, p <0.001) compared with free flap reconstruction. Free flaps had the longest mean operative time compared with the other two groups (unadjusted 578 vs. 440 vs. 326, p <0.001). Pedicled flaps had a lower incidence of bleeding requiring transfusion (adjusted OR = 0.65, CI 0.50-0.85, p = 0.002), and lower incidence of prolonged mechanical ventilation (adjusted OR = 0.33, CI 0.12-0.92, p = 0.034) compared with free flaps. There was no difference in rates of reoperation, hospital readmission, or hospital length-of-stay between pedicled and free flaps. CONCLUSION: Myocutaneous pedicled flaps are associated with higher overall short-term postoperative complications compared with free flaps in head and neck reconstruction, which demonstrate a more favorable morbidity profile without significantly impacting hospital readmission, reoperation, or length-of-stay.

Early postoperative outcomes in implant, pedicled, and free flap reconstruction for breast cancer: an analysis of 23,834 patients from the ACS-NSQIP datasets.

INTRODUCTION: Many patients seek breast reconstruction following mastectomy. Debate exists regarding the best reconstructive option. The authors evaluate outcomes comparing implant, free flap, and pedicled flap reconstruction. METHODS: Patients undergoing implant, pedicled flap, and free flap reconstruction were identified in the 2011-2016 NSQIP database. Demographics were analyzed and covariates were balanced using overlap propensity score. Logistic regression was used for binary outcomes and Gamma GLM for length of stay (LOS). RESULTS: Of 23,834 patients, 87.7% underwent implant, 8.1% free flap, and 4.2% pedicled flap reconstruction. The implant group had the lowest mean operative time (206 min, SD 85.6). Implant patients had less pneumonia (OR 0.09, CI 0.02-0.36, p < 0.01), return to operating room (OR 0.62, CI 0.50-0.75, p < 0.01), venous thromboembolism (VTE) (OR 0.33, CI 0.14-0.79, p = 0.01), postoperative bleeding (OR 0.10, CI 0.06-0.15, p < 0.01), and urinary tract infections (UTI) (OR 0.21, CI 0.07-0.58, p < 0.01) than free flap patients. Pedicled flap patients had less postoperative bleeding (OR 0.69, CI 0.49-0.96, p = 0.03) than free flap patients. Pedicled flap patients had more superficial surgical site infections (p = 0.03), pneumonia (p = 0.02), postoperative bleeding (p < 0.01), VTE (p = 0.04), sepsis (p = 0.05), and unplanned reintubation (p = 0.01) than implant patients. Implant patients had the lowest LOS (1.6 days, p < 0.01). CONCLUSION: Implant reconstruction has less short-term postoperative complications than free flaps and pedicled flap reconstructions. The overall complication rate among all reconstructive modalities remains acceptably low and patients should be informed of all surgical options.

Statistical inference for natural language processing algorithms with a demonstration using type 2 diabetes prediction from electronic health record notes.

The pointwise mutual information statistic (PMI), which measures how often two words occur together in a document corpus, is a cornerstone of recently proposed popular natural language processing algorithms such as word2vec. PMI and word2vec reveal semantic relationships between words and can be helpful in a range of applications such as document indexing, topic analysis, or document categorization. We use probability theory to demonstrate the relationship between PMI and word2vec. We use the theoretical results to demonstrate how the PMI can be modeled and estimated in a simple and straight forward manner. We further describe how one can obtain standard error estimates that account for within-patient clustering that arises from patterns of repeated words within a patient's health record due to a unique health history. We then demonstrate the usefulness of PMI on the problem of predictive identification of disease from free text notes of electronic health records. Specifically, we use our methods to distinguish those with and without type 2 diabetes mellitus in electronic health record free text data using over 400 000 clinical notes from an academic medical center.

Longitudinal follow-up after telephone disclosure in the randomized COGENT study.

PURPOSE: To better understand the longitudinal risks and benefits of telephone disclosure of genetic test results in the era of multigene panel testing. METHODS: Adults who were proceeding with germline cancer genetic testing were randomized to telephone disclosure (TD) with a genetic counselor or in-person disclosure (IPD) (i.e., usual care) of test results. All participants who received TD were recommended to return to meet with a physician to discuss medical management recommendations. RESULTS: Four hundred seventy-three participants were randomized to TD and 497 to IPD. There were no differences between arms for any cognitive, affective, or behavioral outcomes at 6 and 12 months. Only 50% of participants in the TD arm returned for the medical follow-up appointment. Returning was associated with site (p < 0.0001), being female (p = 0.047), and not having a true negative result (p < 0.002). Mammography was lower at 12 months among those who had TD and did not return for medical follow-up (70%) compared with those who had TD and returned (86%) and those who had IPD (87%, adjusted p < 0.01). CONCLUSION: Telephone disclosure of genetic test results is a reasonable alternative to in-person disclosure, but attention to medical follow-up may remain important for optimizing appropriate use of genetic results.

Longitudinal outcomes with cancer multigene panel testing in previously tested BRCA1/2 negative patients.

Although multigene panel testing (MGPT) is increasingly utilized in clinical practice, there remain limited data on patient-reported outcomes. BRCA 1/2 negative patients were contacted and offered MGPT. Patients completed pre- and posttest counseling, and surveys assessing cognitive, affective and behavioral outcomes at baseline, postdisclosure and 6 and 12 months. Of 317 eligible BRCA1/2 negative patients who discussed the study with research staff, 249 (79%) enrolled. Decliners were more likely to be older, non-White, and recruited by mail or email. Ninety-five percent of enrolled patients proceeded with MGPT. There were no significant changes in anxiety, depression, cancer specific distress or uncertainty postdisclosure. There were significant but small increases in knowledge, cancer-specific distress and depression at 6-12 months. Uncertainty declined over time. Those with a VUS had significant decreases in uncertainty but also small increases in cancer specific distress at 6 and 12 months. Among those with a positive result, medical management recommendations changed in 26% of cases and 2.6% of all tested. Most BRCA1/2 negative patients have favorable psychosocial outcomes after receipt of MGPT results, although small increases in depression and cancer-specific worry may exist and may vary by result. Medical management changed in few patients.

Inflammation and breast density among female Chinese immigrants: exploring variations across neighborhoods.

PURPOSE: We examined associations of inflammation with breast density, a marker of breast cancer risk, among female Chinese immigrants and explored whether associations varied by neighborhood environment. METHODS: Assessments of serum C-reactive protein (CRP), soluble tumor necrosis factor receptor 2 (sTNFR2), and breast density were performed among 401 Chinese immigrants across the Philadelphia region. Participant addresses were geocoded, with the majority residing in areas representing traditional urban enclaves (i.e., Chinatown and South Philadelphia) or an emerging enclave with a smaller, but rapidly growing Chinese immigrant population (i.e., the Near Northeast). The remainder was classified as residing in non-enclaves. RESULTS: In multivariable adjusted regression models, CRP was inversely associated with dense breast area (p = 0.01). Levels of sTNFR2 were also inversely associated with dense breast area, but these associations varied by neighborhood (interaction p = 0.01); specifically, inverse associations were observed among women residing in the emerging enclave (p = 0.03), but not other neighborhoods. CONCLUSIONS: Among Chinese immigrant women, aggregate analyses that do not take neighborhood context into consideration can mask potential variations in association of inflammatory markers with breast density. Future studies should consider how neighborhood contextual factors may contribute to differential risk pathways.

Preferences for in-person disclosure: Patients declining telephone disclosure characteristics and outcomes in the multicenter Communication Of GENetic Test Results by Telephone study.

Telephone disclosure of cancer genetic test results is noninferior to in-person disclosure. However, how patients who prefer in-person communication of results differ from those who agree to telephone disclosure is unclear but important when considering delivery models for genetic medicine. Patients undergoing cancer genetic testing were recruited to a multicenter, randomized, noninferiority trial (NCT01736345) comparing telephone to in-person disclosure of genetic test results. We evaluated preferences for in-person disclosure, factors associated with this preference and outcomes compared to those who agreed to randomization. Among 1178 enrolled patients, 208 (18%) declined randomization, largely given a preference for in-person disclosure. These patients were more likely to be older (P = 0.007) and to have had multigene panel testing (P < 0.001). General anxiety (P = 0.007), state anxiety (P = 0.008), depression (P = 0.011), cancer-specific distress (P = 0.021) and uncertainty (P = 0.03) were higher after pretest counseling. After disclosure of results, they also had higher general anxiety (P = 0.003), depression (P = 0.002) and cancer-specific distress (P = 0.043). While telephone disclosure is a reasonable alternative to in-person disclosure in most patients, some patients have a strong preference for in-person communication. Patient age, distress and complexity of testing are important factors to consider and requests for in-person disclosure should be honored when possible.

Trends in Regionalization of Care and Mortality For Patients Treated With Radical Cystectomy.

BACKGROUND: Regionalization to higher volume centers has been proposed as a mechanism to improve short-term outcomes following complex surgery. OBJECTIVE: The objective of this study was to assess trends in regionalization and mortality for patients undergoing radical cystectomy (RC). RESEARCH DESIGN: An observational study of patients receiving RC in the United States from 2004 to 2013. SUBJECTS: Data for patients receiving RC were extracted from the National Cancer Database. MEASURES: The primary exposure was hospital volume; low-volume hospitals (LVH) included those with <5 RC/year and high-volume hospitals (HVH) were those with ≥30 RC/year. Trends in the volume were assessed, as were 30- and 90-day mortality. Cochrane-Armitage tests were performed for volume, and propensity score-weighted proportional hazard regression was used to assess mortality. RESULTS: A total of 47,028 RC were performed in 1162 hospitals from 2004 to 2013. The proportion of RC at LVH declined from 29% to 17% (P<0.01), whereas that of HVH increased from 16% to 33% (P<0.01). Unadjusted 30- (P=0.02) and 90-day (P<0.001) mortality decreased, and the absolute decrease was greatest at LVH (4.8% vs. 2.6%, P=0.03), whereas rates for HVH remained stable (1.9% vs. 1.4%, P=0.34). Following risk-adjustment, relative to treatment at HVH, treatment at LVH was associated with increased 30-day (hazard ratio: 1.66, 95% CI: 1.53-1.80) and 90-day mortality (hazard ratio: 1.37, 95% confidence interval: 1.30-1.44). CONCLUSIONS: Regionalization of RC to HVH was observed from 2004 to 2013. Treatment at LVH was associated with 66% and 33% relative increases in hazard of death at 30 and 90 days, respectively. These findings support the selective referral of complex cases to higher volume centers.

Prediction of significant estimated glomerular filtration rate decline after renal unit removal to aid in the clinical choice between radical and partial nephrectomy in patients with a renal mass and normal renal function.

OBJECTIVES: To develop a clinically applicable predictive model to quantitate the risk of estimated glomerular filtration rate (eGFR) decline to ≤45 mL/min/1.73 m2 after radical nephrectomy (RN) to better inform decisions between RN and partial nephrectomy (PN). PATIENTS AND METHODS: Our prospectively maintained kidney cancer registry was reviewed for patients with a preoperative eGFR >60 mL/min/1.73 m2 who underwent RN for a localized renal mass. New baseline renal function was indexed. We used multivariable logistic regression to develop a predictive nomogram and evaluated it using receiver-operating characteristic (ROC) analysis. Decision-curve analysis was used to assess the net clinical benefit. RESULTS: A total of 668 patients met the inclusion criteria, of whom 183 (27%) experienced a decline in eGFR to ≤45 mL/min/1.73 m2 . On multivariable analysis, increasing age (P = 0.001), female gender (P < 0.001), and increasing preoperative creatinine level (P < 0.001) were associated with functional decline. We constructed a predictive nomogram that included these variables in addition to comorbidities with a known association with kidney disease, but found that a simplified model excluding comorbidities was equally robust (cross-validated area under the ROC curve was 0.78). Decision-curve analysis showed the net clinical benefit at probabilities >~11%. CONCLUSIONS: The decision to perform RN vs PN is multifaceted. We have provided a simple quantitative tool to help identify patients at risk of a postoperative eGFR of ≤45 mL/min/1.73 m2 , who may be stronger candidates for nephron preservation.

Musashi-2 (MSI2) supports TGF-ß signaling and inhibits claudins to promote non-small cell lung cancer (NSCLC) metastasis.

Non-small cell lung cancer (NSCLC) has a 5-y survival rate of ∼16%, with most deaths associated with uncontrolled metastasis. We screened for stem cell identity-related genes preferentially expressed in a panel of cell lines with high versus low metastatic potential, derived from NSCLC tumors of Kras(LA1/+);P53(R172HΔG/+) (KP) mice. The Musashi-2 (MSI2) protein, a regulator of mRNA translation, was consistently elevated in metastasis-competent cell lines. MSI2 was overexpressed in 123 human NSCLC tumor specimens versus normal lung, whereas higher expression was associated with disease progression in an independent set of matched normal/primary tumor/lymph node specimens. Depletion of MSI2 in multiple independent metastatic murine and human NSCLC cell lines reduced invasion and metastatic potential, independent of an effect on proliferation. MSI2 depletion significantly induced expression of proteins associated with epithelial identity, including tight junction proteins [claudin 3 (CLDN3), claudin 5 (CLDN5), and claudin 7 (CLDN7)] and down-regulated direct translational targets associated with epithelial-mesenchymal transition, including the TGF-ß receptor 1 (TGFßR1), the small mothers against decapentaplegic homolog 3 (SMAD3), and the zinc finger proteins SNAI1 (SNAIL) and SNAI2 (SLUG). Overexpression of TGFßRI reversed the loss of invasion associated with MSI2 depletion, whereas overexpression of CLDN7 inhibited MSI2-dependent invasion. Unexpectedly, MSI2 depletion reduced E-cadherin expression, reflecting a mixed epithelial-mesenchymal phenotype. Based on this work, we propose that MSI2 provides essential support for TGFßR1/SMAD3 signaling and contributes to invasive adenocarcinoma of the lung and may serve as a predictive biomarker of NSCLC aggressiveness.

Anti-Müllerian hormone and risk of ovarian cancer in nine cohorts.

Animal and experimental data suggest that anti-Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case-control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable-adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59-1.67) (Ptrend : 0.91). The association did not differ by age at blood draw or oral contraceptive use (all Pheterogeneity : ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all Pheterogeneity : ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer.

Comparative Effectiveness and Risks of Bowel Preparation Before Elective Colorectal Surgery.

OBJECTIVE: The objective of this study was to determine the relationship between bowel preparation and surgical site infections (SSIs), and also other postoperative complications, after elective colorectal surgery. BACKGROUND: SSI is a major source of postoperative morbidity/costs after colorectal surgery. The value of preoperative bowel preparation to prevent SSI remains controversial. METHODS: We analyzed 32,359 patients who underwent elective colorectal resections in the American College of Surgeons National Surgery Quality Improvement Program database from 2012 to 2014. Univariable and multivariable analyses were performed; propensity adjustment using patient/procedure characteristics was used to account for nonrandom receipt of bowel preparation. RESULTS: 26.7%, 36.6%, 3.8%, and 32.9% of patients received no bowel preparation, mechanical bowel preparation (MBP), oral antibiotics (OA), and MBP + OA, respectively. After propensity adjustment, MBP was not associated with decreased risk of SSI compared with no bowel preparation. In contrast, both OA and OA + MBP were associated with decreased risk of any SSI (adjusted odds ratio 0.49, 95% confidence interval 0.38-0.64; and adjusted odds ratio 0.45, 95% confidence interval 0.40-0.50, respectively) compared with no bowel preparation. OA and MBP + OA were associated with decreased risks of anastomotic leak, postoperative ileus, readmission, and also shorter length of stay (all P < 0.05). Bowel preparation was not associated with increased risk of cardiac/renal complications compared with no preparation. CONCLUSIONS: The use of MBP alone before elective colorectal resection to prevent SSI is ineffective and should be abandoned. In contrast, OA and MBP + OA are associated with decreased risks of SSI and are not associated with increased risks of other adverse outcomes compared with no preparation. Prospective studies to determine the efficacy of OA are warranted; in the interim, MBP + OA should be used routinely before elective colorectal resection to prevent SSI.