Citations

Abstract New gene-editing tools challenge conventional policy proscriptions of research aimed at either human germline gene editing or human enhancement by potentially lowering technical barriers to both kinds of intervention. Some recent gene-editing reports have begun to take up the prospect of germline editing, but most experts are in broad agreement that research should prioritize medical applications over attempts to enhance human traits. However, there is little consensus about what counts as human enhancement in this context, or how to deal with the issues it flags. Moreover, several influential reports interpret medical applications to include disease prevention as well as treatment as a goal for gene-editing research. This challenges the current policy consensus because using gene editing to prevent disease would incidentally facilitate human enhancement applications in a variety of ways. If such research efforts are penalized by policy concerns about enhancement, then their preventive health benefits could be lost. To avoid being caught off guard by such challenges, science policy makers will need to think more carefully about what “prevention” might mean in the gene-editing context, and develop research governance that can anticipate and address the human enhancement concerns it will raise. To accomplish the latter, the scope of policy making will need to expand from its narrow focus on human clinical trials to engage with basic researchers driving the translational pipeline toward preventive gene editing and the science policy makers who have to address its “off-label” uses.

Background: There are conflicting data regarding the impact of obesity on postoperative outcomes following radical cystectomy (RC) and how obesity and malnutrition interact in patients undergoing RC. Objective: To evaluate associations of body mass index (BMI), significant preoperative weight loss, and hypoalbuminemia with 30-day complications and mortality after RC. Methods: Review of the American College of Surgeons National Surgical Quality Improvement Program database identified 2,055 patients who underwent RC (2006-12). Univariate and multivariable logistic regression models were developed to assess associations between hypoalbuminemia (<3.5 g/dL), >10% preoperative weight loss, obesity as characterized by BMI (class I: 30–34.9, II: 35–39.9, III: ≥40 kg/m 2 ), and 30-day complications and mortality. Results: The median BMI of the study cohort was 27.82 kg/m 2 with 22.4% classified as having class I, 7.5% class II, and 4.2% class III obesity, respectively. Hypoalbuminemia and >10% weight loss were present in 16.7% and 3.5%, respectively. Among obese patients, 13.4% had hypoalbuminemia. On multivariable analysis, class I (OR 1.43, p = 0.01), class II (OR 1.92, p < 0.001), and class III (OR 2.32, p < 0.001) obesity and hypoalbuminemia (OR 1.47, p = 0.02) were independently associated with 30-day complications, and class III obesity (OR 2.96, p = 0.02) and hypoalbuminemia (OR 2.33, p = 0.03) were independently associated with 30-day mortality. Conclusion: Increasing class of obesity and hypoalbuminemia were independently associated with increased complications following RC. Hypoalbuminemia and class III obesity were associated with early mortality. This study highlights the fact that malnutrition may coexist in obese patients and underscores the need to identify patients with malnutrition who may be candidates for preoperative nutritional optimization.

AbstractBackgroundOvercoming β-lactam resistance in pathogens such as Pseudomonas aeruginosa is a major clinical challenge. Rapid molecular diagnostics (RMDs) have the potential to inform selection of empiric therapy in patients infected by P. aeruginosa.MethodsIn this study, we used a heterogeneous collection of 197 P. aeruginosa that included multidrug-resistant isolates to determine whether 2 representative RMDs (Acuitas Resistome test and VERIGENE gram-negative blood culture test) could identify susceptibility to 2 newer β-lactam/β-lactamase inhibitor (BL-BLI) combinations, ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (TOL/TAZO).ResultsWe found that the studied RMD platforms were able to correctly identify BL-BLI susceptibility (susceptibility sensitivity, 100%; 95% confidence interval [CI], 97%, 100%) for both BLs-BLIs. However, their ability to detect resistance to these BLs-BLIs was lower (resistance sensitivity, 66%; 95% CI, 52%, 78% for TOL/TAZO and 33%; 95% CI, 20%, 49% for CZA).ConclusionsThe diagnostic platforms studied showed the most potential in scenarios where a resistance gene was detected or in scenarios where a resistance gene was not detected and the prevalence of resistance to TOL/TAZO or CZA is known to be low. Clinicians need to be mindful of the benefits and risks that result from empiric treatment decisions that are based on resistance gene detection in P. aeruginosa, acknowledging that such decisions are impacted by the prevalence of resistance, which varies temporally and geographically.

521 Background: S0221 investigated weekly vs q 2 week dosing of doxorubicin/cyclophosphamide (AC) and paclitaxel (P) in patients (pts) with high risk early breast cancer as previously reported (JCO 33:58-64, 2015). After enrollment of 2716 pts randomization to the two AC arms was stopped for futility and an additional 578 pts received 4 cycles of q 2 week AC and were randomized to P weekly (Pw) or P q 2 weeks (P2). We report updated results of the original trial design and the first report of the 578 pts treated with AC x 4 and Pw x 12 or P2 x 6. Methods: Between December 2003 and November 2010, 2716 pts were randomized in a 2x2 factorial design to 1) 15 weeks of weekly AC (A 24 mg/m2/week and C 60 mg/m2/day po) vs 6 cycles of q 2 week AC (A 60 mg/m2 and C 600 mg/m2) and 2) Pw (paclitaxel 80 mg/m2/week x 12) vs P2 (paclitaxel 175 mg/m2 q 2 weeks x 6), with growth factor support as previously described. After study amendment 578 patients received 4 cycles of q 2 week AC followed by Pw or P2. Updated survival was assessed using log-rank tests and Cox regression models. Results: At a median follow-up of 8.5 years, among the pts treated in the original protocol, there were no significant differences among the four treatments for DFS (p=0.21) or OS (p=0.08). The triple-negative subset had worse DFS (P<0.001) than the HER2-positive or ER/PR+/HER2- subsets, with 5 year DFS of 75% vs 83% and 84%, respectively. While we previously found in the triple negative subset that the arm using q 2 weeks for both AC and paclitaxel was marginally superior, the differences among the arms are no longer significant for DFS (p=0.12) or OS (p=0.11). Among the 578 pts assigned ACx4 and randomized to Pw v P2 there were no overall differences in DFS (p=0.70) or OS (p=0.63) after 4.4 years median follow-up. Conclusions: There were no significant differences in DFS or OS between any of the schedules with extended follow-up in the original cohort and no difference in outcome by paclitaxel schedule for the 578 additional patients in the revised protocol. Either paclitaxel schedule may be recommended, with selection based on toxicity, cost, or patient preference rather than efficacy. Support: NCI grants CA32102, CA38926, CA21115, CA21076, CA77597, CA25224, CA77202, CCSRI15469, and Amgen, Inc. Clinical trial information: NCT00070564.

Objective The objective of this research paper is to compare antibiotic treatment, follow-up rates, and types of follow-up encounters among eVisits, phone calls, and in-person encounters for pediatric conjunctivitis. Study design A retrospective chart review of pediatric patients evaluated for conjunctivitis between May 1, 2016 and May 1, 2017, was performed. A total of 101 eVisits, 202 in-person retail clinic visits, and 202 nurse phone calls for conjunctivitis were manually reviewed for outcomes. Exclusion criteria included previous encounter for conjunctivitis in the past 14 days, treatment with an oral antibiotic at the initial encounter, or patient outside Minnesota at the time of encounter. Comparison among the three encounter types with regard to follow-up rates, follow-up encounter type within 14 days of initial evaluation, and prescribing rates was performed. Results Patients completing non-face-to-face encounters were significantly more likely to have follow-up care (34.6% and 45.5%) than those who had a face-to-face visit at the retail clinic (7.4%), p ≤ 0.0001. Patients initially evaluated by eVisit were more likely to have follow-up at the retail clinic while patients initially evaluated by phone call were more likely to have follow-up in their primary care office. Treatment rates with antibiotics were significantly higher in phone call encounters (41.6%) than in eVisits (25.7%) or face-to-face encounters (19.8%), p < 0.0001. Conclusions Non-face-to-face visits have significantly higher rates of follow-up when compared to face-to-face encounters. Antibiotic prescribing is greater with phone call triage encounters; however, there was no significant difference in antibiotic prescribing rates between eVisits and face-to-face visits. Follow-up type varied according to site of initial encounter.

Introduction and Objective: Conflicting data exists regarding the impact of body mass index (BMI) on postoperative outcomes following surgery for renal malignancies (RM). Herein, we investigated associations between obesity, hypoalbuminemia, and/or significant weight loss in the preoperative period, and risk complications and mortality within 30 days of radical (RN) or partial nephrectomy (PN). Materials and Methods: Review of the American College of Surgeons National Surgical Quality Improvement Program database identified 8,618 patients treated with PN or RN for RM between 2005 and 2012. Univariate and multivariable logistic regression models were developed to assess associations between hypoalbuminemia (<3.5 g/dl), >10% weight loss within 6 months of surgery, obesity (BMI >30 kg/m 2 ), and 30-day major complications and mortality. Results: Median BMI was 29.2 kg/m 2 with 24.9%, 11.9%, and 8.2% having class I, II, and III obesity, respectively. Weight loss of >10% was observed in 2.6% and 15.4% had preoperative albumin<3.5 g/dl. There were 1,802 complications (20.9%) and 88 deaths within 30 days (1.0%). On multivariable analysis, BMI ≥40 kg/m 2 (OR 1.3, p = 0.04), >10% weight loss (OR 1.9, p < 0.001) and hypoalbuminemia (OR 1.5, p < 0.001) were independently associated with 30-day complications, while only >10% weight loss was independently associated with 30-day mortality (OR 2.4, p = 0.03). Conclusions: Extreme obesity, hypoalbuminemia, and significant weight loss were independently associated with risk of significant complications following PN or RN while only significant preoperative weight loss was associated with early mortality, underscoring the need to further understand the utility of moderating these risk factors in the perioperative period.