No abstract

Background: The BREAST-Q is the only questionnaire specific to bilateral breast reduction that was developed according to federal and international standards. Many payors mandate minimum resection weights for preapproval, despite lacking supportive evidence for this practice. This study aimed to assess changes in BREAST-Q scores after bilateral breast reduction, and determine whether compliance with Schnur requirements impacts improvement in patient-reported outcomes. Methods: Patients presenting for bilateral breast reduction from 2011 to 2017 were asked to complete the BREAST-Q preoperatively and postoperatively. Multivariate regression analysis was performed to isolate factors associated with favorable outcomes. Results: Complete data were available for 238 patients. Mean time to postoperative BREAST-Q was 213 days. Complications occurred in 31 patients (13.0 percent). Mean preoperative BREAST-Q scores were below normative values (p < 0.001), and mean postoperative scores were above normative values (p < 0.001 for Satisfaction with Breasts, Psychosocial Well-being, and Sexual Well-being; and p = 0.05 for Physical Well-being). Postoperative Physical Well-being scores were similar to normative values for resections less than Schnur (p = 0.32), but below norms for resections greater than Schnur (p < 0.0001). On multivariate regression (n = 230), complication and surgeon experience were the only independent predictors of lesser improvement on the Satisfaction with Breasts subscale. Conclusions: This study is the largest to include both preoperative and postoperative bilateral breast reduction BREAST-Q scores, and to compare multiple subscales to normative data. Scores overwhelmingly increased, regardless of age or Schnur compliance. Complications negatively impacted degree of BREAST-Q improvement. Interestingly, postoperative Physical Well-being was slightly higher in women with non–Schnur-compliant resections. Bilateral breast reduction substantially improves patient welfare, and our data question the validity of insurer-mandated minimum resections. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

The development of reagents and catalysts for the enantioselective allylation of ketones has been an important goal in asymmetric synthesis for many years. Over the past decade, some important and seminal advances have been recorded, but most of these require the use of potentially toxic tin-based allyl reagents.[1] More recently, Chong, [2] Shibasaki, [3] Soderquist, [4] and Yamamoto [5] have recorded truly remarkable advances. With only a few notable exceptions, however, the scope of reactions that gives useful levels of efficiency and enantioselectivity remains limited to aryl methyl, cyclohexenyl methyl, and tert-butyl methyl ketones and structurally related derivatives thereof. There is no current solution at all for the enantioselective allylation of several important classes of ketones, including highly sterically hindered aryl alkyl ketones and diaryl ketones. In addition, only limited success has thus far been recorded in enantioselective ketone crotylation reactions, and no method that can produce both the syn and anti diastereomers with high levels of diastereoand enantioselectivity has been reported. Our own recent investigations into the use of strained allylsilanes [6] for enantioselective aldehyde allylations and crotylations [7]

The opioid epidemic in the United States resulted in 42,000 deaths in 2016, 40% of which involved a prescription opioid. It is estimated that 2 million patients become opioid-dependent after elective, ambulatory surgery each year. There has been increased interest in quantifying the need for postoperative narcotic pain medications for a variety of surgical procedures. However, studies have been limited. We sought to quantify the analgesic usage after one of the most common operations performed in plastic surgery, bilateral breast reduction. In this prospective, observational study, sequential breast reduction patients were contacted by telephone on the evening of postoperative days 3 and 7. Patients were queried as to which analgesic medications were used on the day of the phone call. Data relating to dosage, frequency, and satisfaction with pain control were sought. Patients taking chronic narcotics, postoperative complications requiring surgical intervention, and those unable to be reached after multiple attempts were excluded. Complete data were obtained for 40 patients. Narcotic prescriptions were written for oxycodone, hydromorphone and tramadol, with the number prescribed ranging from 0 to 20 tablets. The median total number used was 6 tablets. Eighty percent of patients used a total of 10 tablets or less. Fifty percent of patients were using only nonnarcotic analgesia by postoperative day 3. Patient-reported satisfaction with pain control was overwhelmingly positive, with 95% being either somewhat satisfied or very satisfied with postoperative pain control. Of those taking any medication on postoperative day 3, only half were using a nonsteroidal anti-inflammatory drug (NSAID) as part of their pain regimen. The number of tablets prescribed after breast reduction surgery varies considerably, and there is no consensus regarding the appropriate number to prescribe. Currently, few patients use all the medication prescribed to them, indicating a high rate of overprescribing. The overwhelming majority are satisfied with their pain control. Most patients use less than 10 tablets of narcotic pain medication after surgery. Acetaminophen is widely used as an adjunct but NSAIDs remain underutilized. Based on these data, we recommend that breast reduction patient's pain is best managed with acetaminophen, NSAIDs, and expectation management.

No abstract

Nearly all colorectal cancers (CRCs) and varied subsets of other cancers have somatic mutations leading to β-catenin stabilization and increased β-catenin/TCF transcriptional activity. Inhibition of stabilized β-catenin in CRC cell lines arrests their growth and highlights the potential of this mechanism for novel cancer therapeutics. We have pursued efforts to develop small molecules that inhibit β-catenin/TCF transcriptional activity. We used xanthothricin, a known β-catenin/TCF antagonist of microbial origin, as a lead compound to synthesize related analogues with drug-like features such as low molecular weight and good metabolic stability. We studied a panel of six candidate Wnt/β-catenin/Tcf-regulated genes and found that two of them (Axin2, Lgr5) were reproducibly activated (9–10 fold) in rat intestinal epithelial cells (IEC-6) following β-catenin stabilization by Wnt-3a ligand treatment. Two previously reported β-catenin/TCF antagonists (calphostin C, xanthothricin) and XAV939 (tankyrase antagonist) inhibited Wnt-activated genes in a dose-dependent fashion. We found that four of our compounds also potently inhibited Wnt-mediated activation in the panel of target genes. We investigated the mechanism of action for one of these (8c) and demonstrated these novel small molecules inhibit β-catenin transcriptional activity by degrading β-catenin via a proteasome-dependent, but GSK3β-, APC-, AXIN2- and βTrCP-independent, pathway. The data indicate the compounds act at the level of β-catenin to inhibit Wnt/β-catenin/TCF function and highlight a robust strategy for assessing the activity of β-catenin/TCF antagonists.

Introduction Insurance companies use minimum resection weight, sometimes based on body surface area (Schnur sliding scale), as a criterion for preapproval and ultimately coverage of reduction mammoplasty. The purpose of this study is to compare the accuracy of subjective resection estimates and estimates calculated by published formulae versus measured resection weights, and to explore the impact of these estimates on insurance preauthorization and payment. Methods A retrospective chart review of bilateral reduction mammaplasties performed at a single academic medical center by seven plastic surgeons from January 2011 to December 2017 was performed. Patients undergoing oncoplastic reduction, simultaneous additional body-contouring procedures, or lacking complete data were excluded. A total of 762 patients were reviewed. Absolute and relative errors between preoperative estimate and actual resection weights were calculated. A subset of patients with requisite breast measurements (n = 579) was examined to compare formula-based with clinical estimates of resection weights. Results Median error was 105 g (14% normalized by resection weight). Frequency of underestimation (40.5%) and overestimation (55.7%) were similar. In 19% (n = 291) of reduced breasts, resection estimate was less than the Schnur requirement. For 5 (2.8%) of these patients, insurers denied coverage explicitly for this reason. Our surgeons' positive predictive value of estimate > Schnur was 86.6%. In 23% (n = 352) of breasts, resection was < Schnur requirement. No insurance claim was denied a posteriori due to resection weight less than Schnur. The formula proposed by Appel et al. produced the most accurate estimates, and is the most likely to produce an estimate < Schnur in nonobese women. Correlations between each surgeon's relative errors and years of faculty experience (r 2 < 0.07) and number of reduced breasts (r 2 = 0.0275) were very weak. Conclusions Resection estimate accuracy varies among surgeons and does not appear to be affected by experience. Because insurers use resection estimates to determine preauthorization, this could be problematic, particularly for surgeons tending to underestimate. However, insurers are inconsistent in application of the Schnur requirement once surgery has been preapproved and its validity as a determinant of medical necessity is in question.

The development of reagents and catalysts for the enantioselective allylation of ketones has been an important goal in asymmetric synthesis for many years. Over the past decade, some important and seminal advances have been recorded, but most of these require the use of potentially toxic tin-based allyl reagents.[1] More recently, Chong, [2] Shibasaki, [3] Soderquist, [4] and Yamamoto [5] have recorded truly remarkable advances. With only a few notable exceptions, however, the scope of reactions that gives useful levels of efficiency and enantioselectivity remains limited to aryl methyl, cyclohexenyl methyl, and tert-butyl methyl ketones and structurally related derivatives thereof. There is no current solution at all for the enantioselective allylation of several important classes of ketones, including highly sterically hindered aryl alkyl ketones and diaryl ketones. In addition, only limited success has thus far been recorded in enantioselective ketone crotylation reactions, and no method that can produce both the syn and anti diastereomers with high levels of diastereoand enantioselectivity has been reported. Our own recent investigations into the use of strained allylsilanes [6] for enantioselective aldehyde allylations and crotylations [7]