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Background Context: Intraoperative detection of a pedicle wall breach implicitly reduces surgical risk, but the reliability of intraoperative neuromonitoring has been contested. Hydroxyapatite has been promulgated to increase pedicle screw resistance and negatively influence the accuracy of electromyography. Purpose: The primary purpose of this experiment is to evaluate the effect of HA on pedicle screw electrical resistance using a controlled laboratory model. Study Design: Controlled Laboratory Study. Methods: Stimulation of pedicle screws was performed in normal saline (0.9% NaCl). The experimental group included eight HA coated (HAC) pedicle screws and matched manufacturer control pedicle screws without HAC (Ti6Al4V). All screws were stimulated at 5, 10-, 15-, 20-, and 25-mm submersion depths. Circuit current return was recorded, and pedicle screw electrical resistance was calculated according to Ohm's Law. Data were assessed for normality and variance. Mann-Whitney U and Kruskal-Wallis tests compared groups with Bonferroni correction for multiple testing. Effect size is reported with 95% confidence intervals (95CI). P-values Results: Current return was detected for all screws (N= 24) following subclinical 8.5 µA stimulation at 5, 10-, 15-, 20-, and 25-mm submersion depths (N=144). The effect estimate of HA on pedicle screw electrical resistance is -0.07 (-0.17-0.01 95CI). The estimated effect of HA on pedicle screw electrical resistance did not differ across manufacturers. Electrical resistance values were inversely related to submersion depth. Electrical resistance values were lower in the experimental group at 10mm (P=0.04), 15mm (P=0.04), and 25mm (P=0.02) submersion depths. The HA effect ranged from -0.03 to -0.08 as submersion depth varied. Conclusion: We found no evidence that HA increased pedicle screw electrical resistance in a matched manufacturer control laboratory model. Clinical Significance: Electrical stimulation of pedicle screws may be reliable for pedicle breach detection in the presence of HA. Future research should investigate if laboratory findings translate to clinical practice and confirm that electrical stimulation of pedicle screws is a reliable method to detect pedicle breach in the presence of HA.

Patients who receive a kidney transplant commonly experience failure of their allograft. Transplant failure often comes with complex management decisions, such as when and how to wean immunosuppression and start the transition to a second transplant or to dialysis. These decisions are made in the context of important concerns about competing risks, including sensitization and infection. Unfortunately, the management of the failed allograft is, at present, guided by relatively poor-quality data and, as a result, practice patterns are variable and suboptimal given that patients with failed allografts experience excess morbidity and mortality compared with their transplant-naive counterparts. In this review, we summarize the management strategies through the often-precarious transition from transplant to dialysis, highlighting the paucity of data and the critical gaps in our knowledge that are necessary to inform the optimal care of the patient with a failing kidney transplant.

Background Risk prediction models for time-to-event outcomes play a vital role in personalized decision-making. A patient’s biomarker values, such as medical lab results, are often measured over time but traditional prediction models ignore their longitudinal nature, using only baseline information. Dynamic prediction incorporates longitudinal information to produce updated survival predictions during follow-up. Existing methods for dynamic prediction include joint modeling, which often suffers from computational complexity and poor performance under misspecification, and landmarking, which has a straightforward implementation but typically relies on a proportional hazards model. Random survival forests (RSF), a machine learning algorithm for time-to-event outcomes, can capture complex relationships between the predictors and survival without requiring prior specification and has been shown to have superior predictive performance. Methods We propose an alternative approach for dynamic prediction using random survival forests in a landmarking framework. With a simulation study, we compared the predictive performance of our proposed method with Cox landmarking and joint modeling in situations where the proportional hazards assumption does not hold and the longitudinal marker(s) have a complex relationship with the survival outcome. We illustrated the use of the RSF landmark approach in two clinical applications to assess the performance of various RSF model building decisions and to demonstrate its use in obtaining dynamic predictions. Results In simulation studies, RSF landmarking outperformed joint modeling and Cox landmarking when a complex relationship between the survival and longitudinal marker processes was present. It was also useful in application when there were several predictors for which the clinical relevance was unknown and multiple longitudinal biomarkers were present. Individualized dynamic predictions can be obtained from this method and the variable importance metric is useful for examining the changing predictive power of variables over time. In addition, RSF landmarking is easily implementable in standard software and using suggested specifications requires less computation time than joint modeling. Conclusions RSF landmarking is a nonparametric, machine learning alternative to current methods for obtaining dynamic predictions when there are complex or unknown relationships present. It requires little upfront decision-making and has comparable predictive performance and has preferable computational speed.

Purpose: To evaluate the impact of an inpatient pharmacy consult on discharge medications following bariatric surgery. Methods: A pharmacy consult for discharge medication review for bariatric surgery patients was instituted at an academic medical center. The intervention included conducting a medication history, reviewing home medications for updates post-bariatric surgery, creating and documenting a discharge medication plan, and providing patient education. The impact of the intervention was evaluated by comparing medication classes, doses, and formulations prescribed during the intervention relative to a historical control group. Results: The study included 85 patients who received pharmacist intervention and 167 patients who did not receive pharmacist intervention following bariatric surgery. The prescription of an extended-release medication at discharge in the intervention group was reduced by 19.3% (28.7% vs. 9.4%, p = 0.0005). For patients on hypertension medications, 94.0% had their regimen reduced in the intervention group compared with 37.5% of patients in the control group (p < 0.001). Of patients on insulin at baseline, 87.5% of patients in the intervention group had dose reductions at discharge vs. 66.7% of patients in the control group (p = 0.37). No patients in the intervention group were discharged with oral antihyperglycemic medications or non-insulin injectable medications vs. 33.3% (p = 0.12) and 20.0% (p = 0.47), respectively, in the control group. Readmission rates at 30 days were insignificantly lower in the intervention group (3.5% vs. 4.2%, p = 1). Conclusions: Clinical pharmacist involvement in the discharge medication reconciliation process for bariatric surgery patients reduced prescribing of unadjusted medication classes, doses, and drug formulations.

Multiple medication changes are common after bariatric surgery, but pharmacist assistance in this setting is not well described. This study evaluated the feasibility and effectiveness of a pharmacy-led initiative for facilitating discharge medicine reconciliation after bariatric surgery. A standardized post-operative pharmacy consult evaluation was conducted on bariatric surgery inpatients at a single academic center starting 1/2/2019. Retrospective chart review evaluated patient characteristics, medication changes, and 30-day outcomes pre-intervention (7/2018–12/2018) and post-intervention (1/2019–12/2019). Two-sample t tests or binomial tests were used for continuous or categorical variables, respectively; a p-value of

Clinicians have few tools to predict the risk of alloimmune injury that would guide immunosuppression management in renal transplant patients. We evaluated human leukocyte antigen (HLA)-DR/DQ molecular mismatch to predict de novo donor-specific antibodies (DSAs) during the first year of transplant and explored how differences in tacrolimus exposure may modulate this risk. HLA-DR and -DQ eplet mismatches were determined between 444 donor-recipient pairs in Denver, Colorado between 2007 and 2013. Previously defined mismatch thresholds stratified recipients into low- (N = 119), intermediate- (N = 153), and high- (N = 172) risk categories. The area under the curve for DSA at 1 year was 0.84 and 0.82 for HLA-DR and HLA-DQ eplet mismatches, respectively. Compared to low-risk patients, there was a graded increase in risk of DR/DQ DSA in intermediate (HR 15.39, 95% CI 2.01-118.09, p = .009) and high-risk (HR 23.81, 95% CI 3.17-178.66, p = 0.002) categories. Intermediate- and high-risk patients with a mean tacrolimus6 ng/ml versus8 ng/ml had increased risk of DR/DQ DSA at 1 year (HR 2.34, 95% CI 1.05-5.22, p = .04). HLA molecular mismatch represents a reproducible, objective, and clinically relevant tool to stratify patients by alloimmune risk and may help guide personalized immunosuppression management.

Esophagogastric junction obstruction (EGJO) post-fundoplication (PF) is difficult to identify with currently available tests. We aimed to assess the diagnostic accuracy of EGJ opening on functional lumen imaging probe (FLIP) and dilation outcome in FLIP-detected EGJO in PF dysphagia. We prospectively collected data on PF patients referred to Esophageal Clinic over 18 months. EGJO diagnosis was made by (a) endoscopist’s description of a narrow EGJ/wrap area, (b) appearance of wrap obstruction or contrast/tablet retention on esophagram, or (c) EGJ-distensibility index (DI)

Surgical procedures in patients with cirrhosis and associated ascites carry significant morbidity and mortality. However, these patients often undergo non-emergent but necessary procedures such as laparoscopic cholecystectomy. The purpose of this study is to determine the impact of cirrhosis with ascites on non-emergent laparoscopic cholecystectomy. The ACS-NSQIP database was queried from 2005 to 2017 for patients undergoing non-emergent laparoscopic cholecystectomy with or without intra-operative cholangiogram. Groups were propensity score matched for age, sex, BMI, smoking, inpatient status, ASA Class, presence of pre-operative SIRS/sepsis, and the individual components of the 5-item modified frailty index. 346,105 patients were identified, 591 of which who had liver-related ascites. Patients without ascites were matched at a 5:1 ratio, producing 2955 controls. Patients with ascites had significantly higher rates of overall morbidity (15.6% vs. 11.3%, p = 0.0039), mortality (3.6% vs. 1.5%, p = 0.0020), and longer hospitalizations (7.4 vs. 4.4 days, p

This study investigated whether a 6-Watt ultraviolet C-lamp was capable of producing photofunctionalization on commercial implants during a medium observation term of 8 weeks. A total of 20 implants were inserted in 5 New Zealand rabbits, with each animal receiving 2 implants per tibia (one photofunctionalized and one untreated), according to a previously established randomization sequence. All implants were inserted by a single surgeon following the manufacturer's instructions. Histological analysis was performed by an evaluator who was blinded to the treatment condition. After 8 weeks of healing, the 2 groups showed no statistically significant differences in terms of bone-to-implant contact. Compared to control implants, the photofunctionalized implants showed improved wettability and more homogenous results. Within the limits of the present study, the use of this 6-W ultraviolet C-lamp, for an irradiation time of 15 minutes at a distance of 15 cm, did not improve the percentages of bone-to-implant contact in rabbits at an osseointegration time of 8 weeks.

There is a lack of literature describing how competitive surgical fellowships are, especially across specialties. Such information would be valuable to prospective candidates, especially as immediate postresidency subspecialty training becomes the norm for general surgery. Match-rates alone may be misleading indicators as programs may not fill positions with unqualified applicants. We propose a simple metric to analyze the competitiveness of various surgical subspecialties to each other and themselves over time.Retrospective cohort study. The Competitive Index is defined as the percentage of filled programs within each specialty divided by the match-rate for that specialty. For ease of comparison, a Normalized Competitive Index (NCI) was developed, normalizing the metric for all specialties in that year to a value of 1.The National Resident Matching Program, The Fellowship Council, and the San Francisco Match publicly available match data from 2009 to 2018.General Surgery Associated Fellowship Applicants (Abdominal Transplant, Colorectal, Surgical Oncology, Minimally Invasive Surgery, Pediatric, Plastic, Critical Care, Thoracic, and Vascular).The overall match rate for all specialties was 74.6% and 84.0% of all programs were filled. Over the past decade, pediatric surgery was significantly more competitive than other specialties (NCI 1.67, p0.0001), while surgical critical care (NCI 0.58, p0.0001) and vascular (NCI 0.90, p0.0492) were significantly less competitive. When comparing the NCI within each specialty from the first 5 years (2009-2013) to the last 5 years, (2014-2018), surgical critical care (NCI 0.54 vs. 0.62, p = 0.0462) and thoracic (NCI 0.74 vs. 1.08, p=0.0025) became significantly more competitive, while transplant (NCI 1.10 vs. 0.92, p = 0.0343) and colorectal (NCI 1.32 vs. 1.09, p = 0.0021) became significantly less competitive.The NCI is a metric which might be useful to prospective applicants and which could be provided annually by organizations sponsoring fellowship matching processes. Further research must be performed to establish what defines a qualified applicant in each specialty.

Challenges for data storage during drug development have become increasingly complex as the pharmaceutical industry expands in an environment that requires on-demand availability of data and resources for users across the globe. While the efficiency and relative low cost of cloud services have become increasingly attractive, hesitancy toward the use of cloud services has decreased and there has been a significant shift toward real-world implementation. Within GxP laboratories, the considerations for cloud storage of data include data integrity and security, as well as access control and usage for users around the globe. In this review, challenges and considerations when using cloud storage options for the storage of laboratory-based GxP data are discussed and best practices are defined.

Evidence has demonstrated that biosynthetic glue for laparoscopic inguinal hernia repair results in decreased pain. However, the two glue sub-types (biologic—fibrin based; synthetic—cyanoacrylate based) have never been compared. This study aims to assess the outcomes of those subtypes. A systematic review of the MEDLINE database was undertaken. Randomized trials assessing the outcomes of laparoscopic inguinal hernia repair with penetrating and glue fixation methods were considered for inclusion and data analysis. Thirteen trials involving 1947 laparoscopic inguinal hernia repairs were identified with eight trials utilizing fibrin and five trials utilizing cyanoacrylate. There were no differences in recurrence or wound infection between the glue subtypes when compared individually to penetrating fixation alone or indirectly to each other. There were non-significant trends in reduction of hematoma and seroma for both glue subtypes when compared to penetrating fixation (OR 0.73, 95% CI 0.39–1.40). There was a significant reduction in urinary retention with glue fixation (pooled results of both sub-types) when compared to penetrating fixation (OR 0.33, 95% CI 0.13–0.83). Glue fixation in laparoscopic inguinal hernia repair reduces the incidence of urinary retention and may reduce the rate of hematoma or seroma formation. As there are no differences in outcomes when comparing fibrin or cyanoacrylate glue, surgeons should choose the glue that is available at the lowest cost at their respective institutions.

Introduction The purpose of this study is to assess how the Hirsch Index (h-index) and other academic metrics change over time for academic minimally invasive surgeons (MIS). Methods Through the Fellowship Council's website, MIS program-directors and associate program-directors were identified in 2017 and again in 2018. Using the Scopus database, the number of publications, citations, self-citations, and h-indices were calculated. Results A total of 222 surgeons were included. The median increase of publications, citations, and h-index were 4, 134, and 1, respectively. 75% of surgeons (166/222) saw their h-index increase. In 2017, 26% of surgeons (57/222) had an increase of their h-index due to self-citation. One-year later, 35% of those surgeons (20/57) no longer demonstrated that change. Conclusion Self-citation remains infrequent within MIS. The h-index of most surgeons will increase over one-year. Many surgeons demonstrating an increase in h-index due to self-citation will see that change eliminated over time.

Background Ionizing radiation is a known cause of female breast cancer, but there have been few studies of the risk after prolonged radiation exposure at low dose rates. Methods This population-based case-control study estimated breast cancer risk after ∼25 years’ exposure to radiation from the Chernobyl accident. Cases (n = 468) were women ≤55 years old when first diagnosed with invasive breast cancer during October 2008 through February 2013, who lived in Bryansk Oblast, Russia at the time of the accident and their diagnoses. Controls, individually matched to cases on birth year, administrative district of residence and urban vs non-urban settlement during the accident, were women without breast cancer who lived in Bryansk Oblast at the time of the accident and on their cases’ diagnosis dates (n = 468). Subjects were interviewed regarding residence, dietary and food source histories to support individualized estimation of their radiation doses to the breast, which ranged from 0.04 − 41 centigray (cGy) (mean 1.3 cGy). Results In multivariable analyses, the odds ratio for breast cancer risk was 3.0 [95% confidence interval (CI): 1.3, 7.0] and 2.7 (95% CI: 1.0, 7.3) in the seventh and eighth dose octiles, respectively, relative to the lowest octile. Analyses of dose effect modification suggested that radiation-related risk may have been higher in women who were younger at the time of the accident and/or at the time of diagnosis. Conclusions This study suggests that prolonged exposure to ionizing radiation at low dose rates can increase risk of breast cancer.

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in either PKD1 or PKD2 genes, is one of the most common human monogenetic disorders and the leading genetic cause of end-stage renal disease. Unfortunately, treatment options for ADPKD are limited. Here we report the discovery and characterization of RGLS4326, a first-in-class, short oligonucleotide inhibitor of microRNA-17 (miR-17), as a potential treatment for ADPKD. RGLS4326 is discovered by screening a chemically diverse and rationally designed library of anti-miR-17 oligonucleotides for optimal pharmaceutical properties. RGLS4326 preferentially distributes to kidney and collecting duct-derived cysts, displaces miR-17 from translationally active polysomes, and de-represses multiple miR-17 mRNA targets including Pkd1 and Pkd2. Importantly, RGLS4326 demonstrates a favorable preclinical safety profile and attenuates cyst growth in human in vitro ADPKD models and multiple PKD mouse models after subcutaneous administration. The preclinical characteristics of RGLS4326 support its clinical development as a disease-modifying treatment for ADPKD., Autosomal dominant polycystic kidney disease (ADPKD) is a leading genetic cause of end-stage renal disease with limited treatment options. Here the authors discover and characterize a microRNA inhibitor as a potential treatment for ADPKD.

Objective Pulmonary embolism (PE) following laparoscopic paraesophageal hernia repair (PEHR) is rare but occurs at a higher frequency than other laparoscopic procedures. We describe a series of patients who developed PEs after PEHR in hopes of capturing potential risk factors for further study. Materials and methods Five cases of PE after PEHR were observed between 2017 and 2018. Individual and perioperative risk factors, and postoperative courses were reviewed. Results Patients had a mean age of 73 years (range, 59 to 86). All were female. Two patients presented acutely. Three patients underwent revisional surgery. The average procedure duration was 248 minutes (range, 162 to 324). All patients had gastrostomy tubes placed. The diagnosis of PE occurred within 3 to 19 days postoperatively. Four were treated with 3 months of oral anticoagulation; 1 was managed expectantly. Conclusions Highly complex cases, marked by revisional status, need for mesh, large hernia size, and percutaneous endoscopic gastrostomy placement are likely at increased risk for PEs. Preoperative venous thromboembolism chemoprophylaxis should be considered in the majority of laparoscopic PEHR patients.

The mechanisms of early failures in dental implant osseointegration are unclear. A possible cause of low levels of bone formation is lubricant contamination on implants during insertion. To explore the impact of lubricant contamination on dental implants, we used 5 New Zealand rabbits and inserted 2 implants per tibia in each animal for a total of 4 implants per animal (20 implants in total). In general, bicorticalization was achieved. The first implant was placed as suggested by the manufacturer with no lubricant used (control). The second implant was placed using a freshly lubricated contra-angle handpiece, which was used only for the test implants. Implant allocation was randomized, and the examining histologist was blinded to the results. All implants were placed by the same surgeon. The animals were maintained in accordance with animal experimentation guidelines. None of the implants failed to osseointegrate. Moreover, no significant difference was observed between the test and control groups. Based on the results of this study, the use of rotary instrument mineral oil lubricant did not jeopardize the osseointegration of dental implants in New Zealand rabbits.

Objective We evaluated 1-year outcomes after platinum chromium everolimus-eluting stents (PtCr-EES) in small versus non-small coronary arteries within a large, diverse sample of men, women, and minorities. Background There exists limited outcomes data on the use of second-generation drug-eluting stent to treat small diameter coronary arteries. Methods We pooled patients from the PLATINUM Diversity and PROMUS Element Plus stent registries. Small-vessel percutaneous coronary intervention (SV-PCI) was defined as ≥1 target lesion with reference vessel diameter (RVD) ≤2.5 mm. Endpoints included major adverse cardiac event (MACE; death, myocardial infarction [MI] or target vessel revascularization [TVR]), target vessel failure (TVF; death related to the target vessel, target vessel MI or TVR) and definite/probable stent thrombosis (ST). Multivariable Cox regression was used to risk-adjust outcomes. Results We included 4,155/4,182 (99%) patients with available RVD, of which 1,607 (39%) underwent small-vessel PCI. SV-PCI was not associated with increased MACE (adjHR 1.02; 95%CI 0.81-1.30) or TVF (adjHR 1.07; 95%CI 0.82-1.39). MI risk was lower in white men compared to women and minorities, both in the setting of SV-PCI (adjHR 0.41; 95%CI 0.23-0.74 and adjHR 0.39; 95%CI 0.20-0.75, respectively) and for non-SV-PCI (adjHR 0.61; 95%CI 0.38-0.99 and adjHR 0.45; 95%CI 0.27-0.74, respectively). There was no significant interaction between RVD and sex or minority status for any endpoint. Conclusion In a large diverse contemporary PCI outcomes database, SV-PCI with PtCr-EES was not associated with increased MACE or TVR and did not account for the increased MI risk noted in women and minorities compared to white men.

The correlation between capital inflows and outflows has increased substantially over time in a sample of 127 advanced and developing countries. We provide evidence that this is a result of an increase in financial globalization (stock of external assets and liabilities). This dominates the effect of an increase in trade globalization (exports plus imports), which reduces the correlation between capital inflows and outflows. In the context of a two-country model with 8 shocks we show that the theoretical impact of financial and trade globalization on the correlation between capital inflows and outflows is consistent with the data.

BackgroundTacrolimus is given post-kidney transplant to suppress the immune system, and the amount of drug in the body is measured frequently. Higher variability over time may be indicative of poor drug adherence, leading to more adverse events. It is important to account for the variation in Tacrolimus, not just the average change over time.MethodsUsing data from the University of Colorado, we compare methods of assessing how the variability in Tacrolimus influences the hazard of de novo Donor Specific Antibodies (dnDSA), an early warning sign of graft failure. We compare multiple joint models in terms of fit and predictive ability. We explain that the models that account for the individual-specific variability over time have the best predictive performance. These models allowed each patient to have an individual-specific random error term in the longitudinal Tacrolimus model, and linked this to the hazard of dnDSA model.ResultsThe hazard for the variance and coefficient of variation (CV) loading parameter were greater than 1, indicating that higher variability of Tacrolimus had a higher hazard of dnDSA. Introducing the individual-specific variability improved the fit, leading to more accurate predictions about the individual-specific time-to-dnDSA.ConclusionsWe showed that the individual’s variability in Tacrolimus is an important metric in predicting long-term adverse events in kidney transplantation. This is an important step in personalizing the dosage of TAC post-transplant to improve outcomes post-transplant.

Performance feedback through peer coaching and rigorous self-assessment is a critical part of technical skills improvement. However, formal collaborative programs using operative video-based skills assessments to generate peer coaching feedback have only been validated among attending surgeons. In this study, we developed a unique longitudinal, simulation video-based laparoscopic skills resident curriculum using video-based peer coaching and evaluated its association with skills acquisition among surgical trainees.The laparoscopic simulation curriculum consists of a pre-practice laparoscopic skill video recording, followed by receipt of directed coaching and feedback on performance from a faculty coach, a peer coach, and self-coaching. Residents then completed 6 weeks of feedback-directed practice and submitted a second post-practice laparoscopic skill video recording of the same skill, which was evaluated by a minimally invasive surgery expert grader. All general surgery residents in a single institution were enrolled, with 107 residents completing the curriculum in its initial 2 years.Overall, more than two-thirds of residents achieved skills proficiency on their expert assessments, with similar rates of residents achieving skills proficiency at all postgraduate year levels. Significant improvements between the pre-practice assessments and post-practice assessments were most frequently seen in the instrument handling, precision, and motionflow categories (P.05 each). Faculty provided the highest number and proportion of closed-loop comments; residents' self-coaching feedback had the lowest number of closed-loop comments, with 83% of self-assessments containing none.In this study, we describe the successful implementation of a longitudinal laparoscopic skills video-based coaching curriculum designed to improve residents' laparoscopic technical abilities through iterative directed practice supplemented by formative closed-loop feedback. This feasible, reproducible, and low-cost simulation curriculum can be adapted to other training programs and skills acquisition endeavors. This program also prepares trainees for ongoing performance feedback after completion of residency through rigorous self-assessment and peer-to-peer coaching.

The collateral channel, whereby an increase in residential house prices leads to an increase in commercial property prices, loosening firm borrowing constraints and increasing firm investment, is weaker when residential and commercial real estate are imperfect substitutes. We enrich the DSGE model of the collateral channel in Liu, Wang, and Zha (2013) by adding a land development sector to allow residential and commercial land to be imperfect substitutes. Bayesian estimation of our structural model based on aggregate U.S. data indicates imperfect substitution between the two types of land. With variance decompositions and impulse responses, we show that the strength of the collateral channel linking residential house prices and firm investment is weaker when the two types of land are imperfect substitutes. When residential and commercial land are assumed to be perfect substitutes, shocks to residential real estate demand explain 20-30% of the variance of total output and 30-40% of the total investment, but with the imperfect degree of substitution that we estimate, the same shocks explain less than 10% of the variance of output and 12-15% of investment.

Background A hyperkinetic gallbladder is defined as a hepatobiliary iminodiacetic acid (HIDA) scan ejection fraction (EF) of >80%. This condition is poorly described, and there is no current consensus on optimal management. The intent of this study was to determine if cholecystectomy improves symptoms in patients with a hyperkinetic gallbladder when compared to those managed nonoperatively and if there were variables predictive of symptom improvement with or without cholecystectomy. Materials and Methods This retrospective study included patients from 3 academic hospitals in the Atlanta metro area between the years 2006 and 2018. All patients with an EF >80% were included. Following voluntary exclusion patients were contacted by phone. Each patient was administered a questionnaire regarding their surgical history, medical management, and current symptom profile via Otago score. Institutional Institutional Review Board approval was obtained. Results 4785 HIDA scans were performed, and 194 reported an EF >80% (incidence 15.7%). 96% of these scans were reported as normal by the radiologist. 68 patients were able to be contacted by phone and completed the questionnaire. 18 patients underwent cholecystectomy, and 89% reported that their symptoms attributed to gallbladder disease were no longer present. 50 patients did not undergo cholecystectomy, and alternate diagnoses, medication prescriptions, diet modification, emergency department visits, and Otago score were higher in this cohort. Discussion Patients who undergo cholecystectomy for a diagnosis of hyperkinetic gallbladder, on average, report improvement in symptoms when compared to patients managed nonoperatively. This study supports the practice of reporting and managing hyperkinetic gallbladders as a pathologic entity.

Background During the COVID-19 pandemic, prioritization of care and utilization of scarce resources are daily considerations in healthcare systems that have never experienced these issues before. Elective surgical cases have been largely postponed, and surgery departments are struggling to correctly and equitably determine which cases need to proceed. A resource to objectively prioritize and track time sensitive cases would be useful as an adjunct to clinical decision-making. Methods A multidisciplinary working group at Emory Healthcare developed and implemented an adjudication tool for the prioritization of time sensitive surgeries. The variables identified by the team to form the construct focused on the patient’s survivability according to actuarial data, potential impact on function with delay in care, and high-level biology of disease. Implementation of the prioritization was accomplished with a database design to streamline needed communication between surgeons and surgical adjudicators. All patients who underwent time sensitive surgery between 4/10/20 and 6/15/20 across 5 campuses were included. Results The primary outcomes of interest were calculated patient prioritization score and number of days until operation. 1767 cases were adjudicated during the specified time period. The distribution of prioritization scores was normal, such that real-time adjustment of the empiric algorithm was not required. On retrospective review, as the patient prioritization score increased, the number of days to the operating room decreased. This confirmed the functionality of the tool and provided a framework for organization across multiple campuses. Conclusions We developed an in-house adjudication tool to aid in the prioritization of a large cohort of canceled and time sensitive surgeries. The tool is relatively simple in its design, reproducible, and data driven which allows for an objective adjunct to clinical decision-making. The database design was instrumental in communication optimization during this chaotic period for patients and surgeons.

Water Quality issues in many Pacific countries are rising, with the increase in coastal populations and associated urban runoff but management requires contamination issues in the aquatic environment to be identified and prioritised. In Vanuatu and Solomon Islands there are few laboratories and resources to assess for the presence or impact of complex chemical contaminants. The extent and impact of chemical contamination of the marine and coastal environment is poorly described. Passive chemical samplers were used to measure a range of aquatic pollutants around the capital cities, Honiara (Solomon Islands) and Port Vila (Vanuatu). We detected a range of chemicals indicative of agricultural and industrial contamination and a few sites had concerning concentrations of specific hydrocarbons and pesticides. The rapid ecotoxicology test, Microtox, indicated toxic impacts in rivers, coastal sites and urban drains This work provides new data on chemical contamination and possible impacts of that contamination for both countries. The techniques could be applied widely across the region to generate critical data for environmental management, guide monitoring efforts and measure the impact of policy or land-use changes.

Tacrolimus (TAC) is the most important agent for maintenance immunosuppression and prevention of immunologic injury to the renal allograft, yet there remains no consensus on how best to monitor drug therapy. Both high TAC intrapatient variability and low TAC time in therapeutic range (TTR) have been associated with risk of de novo donor-specific antibodies (dnDSA). In this study, we hypothesized that the risk associated with high TAC coefficient of variation (CV) is a result of low TAC TTR rather than the variability itself.We analyzed the risk of dnDSA, acute rejection, or death-censored graft loss by non-dosed-corrected TAC CV and TAC TTR during the first posttransplant year in a cohort of 538 patients with a median follow-up period of 4.1 years.Patients with CV44.2% and TTR40% (high intrapatient variability and low TTR) had a high risk of dnDSA (adjusted OR = 4.93, 95% confidence interval = 2.02-12.06, P0.001) and death-censored graft loss by 5 years (adjusted HR = 4.00, 95% confidence interval = 1.31-12.24, P = 0.015) when compared with patients with CV44.2% and TTR ≥40% (high intrapatient variability and optimal TTR), while the latter patients had similar risk to patients with CV44.2% (lower intrapatient variability).These data suggest that previously reported immunologic risk associated with high TAC intrapatient variability is due to time outside of therapeutic range rather than variability in and of itself when evaluating absolute non-dose-corrected TAC levels irrespective of reason or indication.

Individuals with progressive advanced chronic kidney disease (CKD) have a number of treatment modalities to consider before reaching end-stage renal disease. As CKD reaches stage 4, and particularly as glomerular filtration rate approaches 20 mL/min, patients should be informed of kidney transplantation as a treatment option, provided education regarding the transplant process, and be referred to a transplant center unless there are clear contraindications or comorbidities that preclude consideration. There is an unfortunate and dramatic disparity between those who are eligible for transplantation and those who receive a transplant, due in part to referral biases, the comparative shortage of deceased donors, and a lack of acceptance or awareness of living kidney donation as an option. This chapter reviews the transplant landscape, discusses the procedural and pathophysiological considerations for kidney transplantation, and outlines the transplant evaluation process, including inclusion and exclusion criteria.

The collateral channel, whereby an increase in residential house prices leads to an increase in commercial property prices, loosening firm borrowing constraints and increasing firm investment, is weaker when residential and commercial real estate are imperfect substitutes. We enrich the DSGE model of the collateral channel in Liu, Wang, and Zha (2013) by adding a land development sector to allow residential and commercial land to be imperfect substitutes. Bayesian estimation of our structural model based on aggregate U.S. data indicates imperfect substitution between the two types of land. With variance decompositions and impulse responses, we show that the strength of the collateral channel linking residential house prices and firm investment is weaker when the two types of land are imperfect substitutes. When residential and commercial land are assumed to be perfect substitutes, shocks to residential real estate demand explain 20-30% of the variance of output and 30-40% of the variance of investment, but with the imperfect degree of substitution that we estimate, the same shocks explain less than 10% of the variance of output and 12-15% of investment.

The recently published NCRP Commentary No. 27 evaluated the new information from epidemiologic studies as to their degree of support for applying the linear nonthreshold (LNT) model of carcinogenic effects for radiation protection purposes (NCRP 2018 Implications of Recent Epidemiologic Studies for the Linear Nonthreshold Model and Radiation Protection, Commentary No. 27 (Bethesda, MD: National Council on Radiation Protection and Measurements)). The aim was to determine whether recent epidemiologic studies of low-LET radiation, particularly those at low doses and/or low dose rates (LD/LDR), broadly support the LNT model of carcinogenic risk or, on the contrary, demonstrate sufficient evidence that the LNT model is inappropriate for the purposes of radiation protection. An updated review was needed because a considerable number of reports of radiation epidemiologic studies based on new or updated data have been published since other major reviews were conducted by national and international scientific committees. The Commentary provides a critical review of the LD/LDR studies that are most directly applicable to current occupational, environmental and medical radiation exposure circumstances. This Memorandum summarises several of the more important LD/LDR studies that incorporate radiation dose responses for solid cancer and leukemia that were reviewed in Commentary No. 27. In addition, an overview is provided of radiation studies of breast and thyroid cancers, and cancer after childhood exposures. Non-cancers are briefly touched upon such as ischemic heart disease, cataracts, and heritable genetic effects. To assess the applicability and utility of the LNT model for radiation protection, the Commentary evaluated 29 epidemiologic studies or groups of studies, primarily of total solid cancer, in terms of strengths and weaknesses in their epidemiologic methods, dosimetry approaches, and statistical modelling, and the degree to which they supported a LNT model for continued use in radiation protection. Recommendations for how to make epidemiologic radiation studies more informative are outlined. The NCRP Committee recognises that the risks from LD/LDR exposures are small and uncertain. The Committee judged that the available epidemiologic data were broadly supportive of the LNT model and that at this time no alternative dose-response relationship appears more pragmatic or prudent for radiation protection purposes.

The mammalian target of rapamycin (mTOR) pathway has been shown to be central to cyst formation and growth in patients with autosomal dominant polycystic kidney disease (ADPKD). Drugs that suppress mTOR signaling are frequently used as antiproliferative agents for maintenance immunosuppression in patients who have undergone kidney transplantation. The aim of this study was to determine the effect of sirolimus, an mTOR inhibitor, on cyst volume regression in patients with ADPKD who have undergone renal transplantation.In this single-center, prospective, open-label, parallel-group, randomized trial, 23 adult patients with ADPKD who successfully underwent renal transplantation from 2008 to 2012 were subsequently randomized (on a 1:1 basis) to a maintenance immunosuppression regimen with either sirolimus (sirolimus, tacrolimus, prednisone) or mycophenolate (mycophenolate, tacrolimus, prednisone). Total kidney volumes were measured by means of high-resolution magnetic resonance imaging within 2 weeks after transplantation and at 1 year. The primary end point was change in total kidney volume at 1 year.Sixteen patients completed the 1-year study (8 patients in each group). There was a decrease in kidney volume in both the sirolimus group (percentage change from baseline, 20.5%; P .001) and mycophenolate group (percentage change from baseline, 17%; P = .048), but there was no significant difference in percentage change of total kidney volume between the groups (P = .665).In ADPKD patients at 1 year after kidney transplantation, there was a similar decrease in polycystic kidney volume in patients receiving an immunosuppression regimen containing sirolimus compared with patients receiving mycophenolate.

Background: Patients with prior Roux-en-Y gastric bypass (RYGB) operations for weight loss present reconstruction challenges during a pancreaticoduodenectomy (PD). With over 60,000 RYGB performed annually, the increasing odds of encountering such patients during a PD make it imperative to understand the RYGB anatomy and anticipate reconstruction options. This article describes the possible reconstruction options and their rationale. Methods: We reviewed our PD reconstruction options, compared them to what have been described in the literature, and derived a consensus from internal conferences comprising bariatric and hepatopancreatobiliary surgeons to describe known reconstruction options. Results: In general, reconstruction options can include one of three options: (1) remnant gastrectomy, (2) preservation of gastric remnant, or (3) reversal of gastric bypass. Conclusion: This article describes individualized reconstruction options for RYGB patients undergoing PD. The reconstruction options can ...

When used in appropriate patient populations, fast-track extubation (FTE) anesthetic techniques and intensive care unit (ICU) protocols safely reduce intubation times, ICU length of stay, and resource utilization. The authors hypothesized that perioperative provider debriefing on success or failure of FTE would improve FTE success. This retrospective observational study included consecutive patients undergoing elective coronary artery bypass graft (CABG), valve, or combined CABG/valve surgery between February 2015 and May 2016 (N = 313). Throughout the intervention period, a briefing was distributed on postoperative day 1 to the anesthesiology providers responsible for operative care of the patient detailing success or failure of FTE and perioperative characteristics. The preintervention FTE success rate of 55.6% significantly improved to 72.8% in the intervention group ( P = .022). When combined with a continuous interdepartmental review process, provider debriefing improved FTE success. Perioperative provider debriefing requires minimal resources for implementation and can easily be replicated in other cardiac surgery centers.

Neuropathic pain is a debilitating, chronic condition with a significant unmet need for effective treatment options. Recent studies have demonstrated that in addition to neurons, non-neuronal cells such as microglia contribute to the initiation and maintenance of allodynia in rodent models of neuropathic pain. The Ca2+- activated K+ channel, KCa3.1 is critical for the activation of immune cells, including the CNS-resident microglia. In order to evaluate the role of KCa3.1 in the maintenance of mechanical allodynia following peripheral nerve injury, we used senicapoc, a stable and highly potent KCa3.1 inhibitor. In primary cultured microglia, senicapoc inhibited microglial nitric oxide and IL-1β release. In vivo, senicapoc showed high CNS penetrance and when administered to rats with peripheral nerve injury, it significantly reversed tactile allodynia similar to the standard of care, gabapentin. In contrast to gabapentin, senicapoc achieved efficacy without any overt impact on locomotor activity. Together, the data demonstrate that the KCa3.1 inhibitor senicapoc is effective at reducing mechanical hypersensitivity in a rodent model of peripheral nerve injury.

Ornamental fish have been legally harvested since the 1930's but in the 60's, cyanide fishing was first documented. Target fish exposed to the chemical are temporarily paralysed making them easier to catch, but with high post-capture mortality and significant ecological impacts, its use is banned in most exporting countries. To differentiate illegally caught fish from those sustainably collected, efforts to develop a post-collection detection test began nearly 30 years ago. However, even the most promising approach has been questioned by other researchers as unrepeatable under different experimental conditions. In this paper we summarise the evidence-base for establishing a cyanide detection test for live fish by evaluating current approaches. We describe the key knowledge gaps which continue to limit our progress in implementing a screening programme and highlight some alternative solutions which may provide greater short to medium term opportunities to prevent the illegal practise before fish enter the supply chain.

Background The impact of race/ethnicity on coronary stent outcomes in women is unknown. We compared baseline characteristics, social determinants of health, and 1-year outcomes in female African Americans (AA) and Hispanic/Latinas (HL) versus white women after coronary everolimus-eluting stent implantation in all-comer patients. Methods and Results We pooled 1863 women from the PLATINUM Diversity (n=1057 women) and PROMUS ELEMENT PLUS (n=806 women) postapproval studies, with some overlap in study sites. Social determinants of health data were only available for PLATINUM Diversity. The primary end point was 1-year major adverse cardiac events (death, myocardial infarction, or target vessel revascularization). Outcomes were risk adjusted using multivariate Cox regression. The study sample comprised 1417 white (76.1%, reference group), 296 AA (15.9%), and 107 HL (5.7%) women. AA were older, and both AA and HL had more diabetes mellitus and hypertension than white women. AA had larger reference vessel diameters but less lesion calcification, whereas HL had less lesion tortuosity but more calcification. Compared with white women, there was a trend toward higher unadjusted 1-year major adverse cardiac events in AA (12.0% versus 8.0%; P =0.06) but similar rates in HL (11.0% versus 8.0%; P =0.32), and after risk adjustment, there were no differences (AA women: hazard ratio, 1.47; 95% CI, 1.00–2.17; HL women: hazard ratio, 1.33; 95% CI, 0.71–2.44). AA had a 3-fold higher adjusted risk of 1-year myocardial infarction (hazard ratio, 3.45; 95% CI, 1.72–7.14; P =0.01) and increased risk of target vessel revascularization (hazard ratio, 1.82; 95% CI, 1.10–2.94; P =0.02). Independent predictors of major adverse cardiac events included renal disease, prior myocardial infarction, silent ischemia, history of stroke, and multivessel disease. Conclusions Race and ethnicity confer heterogeneity in women undergoing everolimus-eluting stent implantation. Despite more comorbidities and less favorable social determinants of health, AA and HL women have similar 1-year major adverse cardiac events to white women, although AA women seem to have a higher risk of 1-year myocardial infarction. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02240810.

Over the past twenty-five years, central bank communications have undergone a major revolution. Central banks that previously shrouded themselves in mystery now embrace social media to get their message out to the widest audience. The volume of information about monetary policy that the Federal Open Market Committee (FOMC) now releases dwarfs what it was releasing a quarter century ago. This chapter focuses on just one channel of FOMC communications, the postmeeting statement. It documents how this has become more detailed over time. Then daily financial-market data are used to estimate a daily time series of US monetary policy shocks. These shocks on Fed statement release days have gotten larger as the statement has gotten longer and more detailed, and the chapter shows that the length and complexity of the statement have a direct effect on the size of the monetary policy shock following a Fed decision.

Percutaneous Endoscopic Gastrostomy (PEG) is an infrequent adjunct in elective paraesophageal hernia repair (PEHR). Guidelines denote that PEG “may facilitate postoperative care in selected patients.” Though there is sparse literature defining which patients may benefit. The purpose of this study is to determine factors associated with simultaneous PEG placement during PEHR and their subsequent outcomes. The NSQIP database was queried from 2011 to 2016 for patients undergoing elective laparoscopic PEHR. Cases were excluded if PEHR or fundoplasty was not the primary procedure, a concomitant bariatric procedure was performed, or if the primary surgeon was not a general or cardiothoracic surgeon. Groups were Propensity Score Matched for age, BMI, and ASA Class. 15700 patients were identified, 371 who underwent simultaneous PEG placement (2.4%). Non-PEG patients were matched at a 5:1 ratio, producing 1855 controls. PEG patients had higher rates of pre-operative dyspnea (OR 1.45, p = 0.0110), pre-operative weight loss (OR 2.87, p = 0.0001), and lower pre-operative albumin (3.92 vs. 4.01, p = 0.0129). PEG patients had more intra-operative contamination (mean Wound Classification 1.54 vs. 1.38, p

National Council on Radiation Protection and Measurements Commentary 27 examines recent epidemiologic data primarily from low-dose or low dose-rate studies of low linear-energy-transfer radiation and cancer to assess whether they support the linear no-threshold model as used in radiation protection. The commentary provides a critical review of low-dose or low dose-rate studies, most published within the last 10 y, that are applicable to current occupational, environmental, and medical radiation exposures. The strengths and weaknesses of the epidemiologic methods, dosimetry assessments, and statistical modeling of 29 epidemiologic studies of total solid cancer, leukemia, breast cancer, and thyroid cancer, as well as heritable effects and a few nonmalignant conditions, were evaluated. An appraisal of the degree to which the low-dose or low dose-rate studies supported a linear no-threshold model for radiation protection or on the contrary, demonstrated sufficient evidence that the linear no-threshold model is inappropriate for the purposes of radiation protection was also included. The review found that many, though not all, studies of solid cancer supported the continued use of the linear no-threshold model in radiation protection. Evaluations of the principal studies of leukemia and low-dose or low dose-rate radiation exposure also lent support for the linear no-threshold model as used in protection. Ischemic heart disease, a major type of cardiovascular disease, was examined briefly, but the results of recent studies were considered too weak or inconsistent to allow firm conclusions regarding support of the linear no-threshold model. It is acknowledged that the possible risks from very low doses of low linear-energy-transfer radiation are small and uncertain and that it may never be possible to prove or disprove the validity of the linear no-threshold assumption by epidemiologic means. Nonetheless, the preponderance of recent epidemiologic data on solid cancer is supportive of the continued use of the linear no-threshold model for the purposes of radiation protection. This conclusion is in accord with judgments by other national and international scientific committees, based on somewhat older data. Currently, no alternative dose-response relationship appears more pragmatic or prudent for radiation protection purposes than the linear no-threshold model.

Since the Qing dynasty, the relationship between the apocrypha and literature has concerned scholars working on the Wenxuan 文選 (Selections of Refined Writings) and Wenxin diaolong 文心雕龍 (The Literary Mind and the Carving of Dragons). Apocryphal texts emerged in the Han dynasty under the guise of the Six Classics authored by Confucius, as a body of sacred documents explaining the mandates of former rulers or the induction between the celestial and the human. Also containing genealogies of sacred rulers, legends and ancient histories, astronomical and geographical knowledge, and auspicious omens resulting from the correspondence between the celestial and the human, these texts offered abundant resources to authors from the Han, Wei, and Six Dynasties, through the Sui and Tang. Reliance on such a canon as a foundation inevitably yielded some skepticism among scholars as to the veracity of their sources; nonetheless, their literary value was always affirmed. The rhapsodic prose-poetic tradition of the Han dynasty was itself fostered by the exaggerated descriptive style of apocryphal texts.

What does music convey to people living within a culture? How is it understood? How should we approach the study of music when we want to attain a synthetic and comprehensive view of musical activities in human culture? This article explores the cultural interface of the traditional Chinese musical instrument, the guqin . It brings to light the interconnections of ideas and images of this instrument with the expressive resources of Chinese culture, and it studies the symbolism of this music in terms of its orientations toward cosmological views of life, human comportment, poetic values, and spiritual attainment. By tracing the networks of symbolic meaning throughout the cultural fields of Chinese life, one can arrive at a deeper understanding of the thoroughgoing resonance of musical performances in this part of the world.

Frailty is a decrease in physiologic reserve that is separate from the normal aging process. Previously, an 11-item modified frailty index (mFI) using NSQIP variables predicted outcomes for surgical patients. We aim to validate a condensed 5-item mFI in ventral hernia patients and determine outcomes and the relative impact of each frailty variable. The NSQIP database was queried from 2011 to 2016 for patients undergoing VHR. Spearman’s rho correlation was used to determine the degree of correlation between 11-item and 5-item mFI raw frailty scores. Chi squared testing was used to determine odds ratios (95% CI) for accumulating frailty variables in both indices with regard to complications vs a baseline of zero variables present on the 11-item scale. Complications were defined by the Clavien–Dindo (CD) classification. Univariate and multivariate analyses were performed on each frailty variable to determine their relative weighted impacts on outcomes. 97,905 patients (99.45%) had all five frailty variables recorded. Only 11,549 patients (11.73%) had all variables from the 11-item mFI. No difference existed between groups for the five mutually shared frailty variables, BMI, emergent vs non-emergent procedures, operative time, or operative approach. For accumulating variables in both indices, the 5-item mFI predicts incidence of any complications, major complications, and discharge not to home similarly to the 11-item mFI. The most significantly weighted variable for complications and discharge not to home is functional status. A 5-item mFI accurately predicts outcomes similar to the validated 11-item mFI and captures more patients for analysis.