Impact of Surgeon Workload on Pregnancy Outcomes in Surgical Trainees and Faculty.

OBJECTIVE: To investigate the association between workload and pregnancy outcomes among US surgical faculty and trainees. SUMMARY BACKGROUND DATA: Despite the increased risk of pregnancy associated complications among surgeons, most US institutions do not have formalized support to help sustain a healthy pregnancy in surgeons. METHODS: An anonymous self-administered Qualtrics survey was distributed electronically to US surgeons across all surgical specialties. Female surgical trainees/faculty with current or previous pregnancy were invited to participate. Data pertaining to demographics, workload, and pregnancy outcomes were collected for each individual pregnancy resulting in live birth. Multivariate analysis was used to assess for workload and outcomes, controlling for age, race, gravidity, and use of assisted reproductive technology. A significance level of 0.0056 was used for each outcome (Bonferroni multiple-testing adjustment 0.05/9). RESULTS: 817 surgeons experiencing 1348 pregnancies resulting in live birth were included. The mean (SD) age at first live birth was 32(4). The most prevalent major and neonatal complications included preeclampsia/gestational hypertension (n=196, 14.5%) and preterm delivery (n=179, 12.8%), respectively. Most institutions did not have a policy regarding workload modification (n=1189, 88.5%). Most surgeons did not modify their workload (n=862, 63.9%). When looking at individual workload metrics, feeling overworked during the last week of pregnancy correlated with risk of major complication (P=0.0001), preeclampsia/gestational hypertension (P=0.0003), and intra/post-partum complication (P=0.0001). Association with unplanned cesarean section (P=0.0096) and preterm delivery (P=0.0036) reached nominal significance. CONCLUSIONS: Most surgeons do not modify their workload during pregnancy, potentially contributing to feeling overworked and peri-partum complications. There is an urgent need for a cultural shift and institutional policies to safeguard the health and wellbeing of pregnant surgeons.

Efficacy of SPR720 in murine models of non-tuberculous mycobacterial pulmonary infection.

BACKGROUND: Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide, with Mycobacterium avium complex (MAC) and Mycobacterium abscessus as the predominant pathogens. Current treatments are poorly tolerated and modestly effective, highlighting the need for new treatments. SPR719, the active moiety of the benzimidazole prodrug SPR720, inhibits the ATPase subunits of DNA gyrase B, a target not exploited by current antibiotics, and therefore, no cross-resistance is expected with standard-of-care (SOC) agents. OBJECTIVES: To evaluate the in vitro activity of SPR719 against MAC and M. abscessus clinical isolates, including those resistant to SOC agents, and in vivo efficacy of SPR720 in murine non-tuberculous mycobacteria (NTM) pulmonary infection models. METHODS: NTM isolates were tested for susceptibility to SPR719. Chronic C3HeB/FeJ and severe combined immunodeficient murine models of pulmonary infection were used to assess efficacy of SPR720 against MAC and M. abscessus, respectively. RESULTS: SPR719 was active against MAC (MIC90, 2 mg/L) and M. abscessus (MIC90, 4 mg/L) clinical isolates. Efficacy of SPR720 was demonstrated against MAC pulmonary infection, both as a monotherapy and in combination with SOC agents. SPR720 monotherapy exhibited dose-dependent reduction in bacterial burden, with the largest reduction observed when combined with clarithromycin and ethambutol. Efficacy of SPR720 was also demonstrated against M. abscessus pulmonary infection where monotherapy exhibited a dose-dependent reduction in bacterial burden with further reductions detected when combined with SOC agents. CONCLUSIONS: In vitro activity of SPR720 against common NTM pathogens and efficacy in murine infections warrant the continued clinical evaluation of SPR720 as a new oral option for the treatment of NTM-PD.

Evaluation of Tebipenem Hydrolysis by ß-Lactamases Prevalent in Complicated Urinary Tract Infections.

Tebipenem pivoxil is the first orally available carbapenem antibiotic and has been approved in Japan for treating ear, nose, and throat and respiratory infections in pediatric patients. Its active moiety, tebipenem, has shown potent antimicrobial activity in vitro against clinical isolates of Enterobacterales species from patients with urinary tract infections (UTIs), including those producing extended-spectrum ß-lactamases (ESBLs) and/or AmpC ß-lactamase. In the present study, tebipenem was tested for stability to hydrolysis by a set of clinically relevant ß-lactamases, including TEM-1, AmpC, CTX-M, OXA-48, KPC, and NDM-1 enzymes. In addition, hydrolysis rates of other carbapenems, including imipenem, meropenem, and ertapenem, were determined for comparison. It was found that, similar to other carbapenems, tebipenem was resistant to hydrolysis by TEM-1, CTX-M, and AmpC ß-lactamases but was susceptible to hydrolysis by KPC, OXA-48, and NDM-1 enzymes with catalytic efficiency values (kcat/Km) ranging from 0.1 to 2 × 106 M-1s-1. This supports the reported results of antimicrobial activity of tebipenem against ESBL- and AmpC-producing but not carbapenemase-producing Enterobacterales isolates. Considering that CTX-M and AmpC ß-lactamases represent the primary determinants of multidrug-resistant complicated UTIs (cUTIs), the stability of tebipenem to hydrolysis by these enzymes supports the utility of its prodrug tebipenem, tebipenem pivoxil hydrobromide (TBP-PI-HBr), as an oral therapy for adult cUTIs.

Impact of enhanced recovery protocols after pancreatoduodenectomy: meta-analysis.

BACKGROUND: This individual-patient data meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared with conventional care on postoperative outcomes in patients undergoing pancreatoduodenectomy. METHODS: The Cochrane Library, MEDLINE, Embase, Scopus, and Web of Science were searched systematically for articles reporting outcomes of ERAS after pancreatoduodenectomy published up to August 2020. Comparative studies were included. Main outcomes were postoperative functional recovery elements, postoperative morbidity, duration of hospital stay, and readmission. RESULTS: Individual-patient data were obtained from 17 of 31 eligible studies comprising 3108 patients. Time to liquid (mean difference (MD) -3.23 (95 per cent c.i. -4.62 to -1.85) days; P < 0.001) and solid (-3.84 (-5.09 to -2.60) days; P < 0.001) intake, time to passage of first stool (MD -1.38 (-1.82 to -0.94) days; P < 0.001) and time to removal of the nasogastric tube (3.03 (-4.87 to -1.18) days; P = 0.001) were reduced with ERAS. ERAS was associated with lower overall morbidity (risk difference (RD) -0.04, 95 per cent c.i. -0.08 to -0.01; P = 0.015), less delayed gastric emptying (RD -0.11, -0.22 to -0.01; P = 0.039) and a shorter duration of hospital stay (MD -2.33 (-2.98 to -1.69) days; P < 0.001) without a higher readmission rate. CONCLUSION: ERAS improved postoperative outcome after pancreatoduodenectomy. Implementation should be encouraged.

Enhanced recovery protocols consist of interdisciplinary interventions aimed at standardizing care and reducing the impact of surgical stress. They often include a short period of preoperative fasting during the night before surgery, early removal of lines and surgical drains, early food intake and mobilization out of bed on the day of surgery. This study gives a summary of reports assessing such care protocols in patients undergoing pancreatic head surgery, and assesses the impact of these protocols on functional recovery in an analysis of individual-patient data. The study revealed the true benefits of enhanced recovery protocols, including shorter time to food intake, earlier bowel activity, fewer complications after surgery, and a shorter hospital stay compared with conventional care.

National recurrence of pancreatitis and readmissions after biliary pancreatitis.

BACKGROUND: National and international guidelines support early cholecystectomy after mild gallstone pancreatitis but a recent nationwide study suggested these recommendations are not universally followed. Our study sought to quantify the national utilization of same hospitalization cholecystectomy versus non-operative management (NOM) and its association with pancreatitis recurrence, readmissions, and costs after mild gallstone pancreatitis (GP). METHODS: Adult patients admitted with mild GP were identified from the Nationwide Readmission Database 2010-2015. Primary outcomes included the rate of cholecystectomy during the index admission as well as pancreatitis recurrence and readmission at 30 and 180 days (30d, 180d) comparing NOM to same hospitalization cholecystectomy. Mortality upon readmission, total length of stay (LOS), and total costs (combined index-readmission hospital costs) were also explored. Cox proportional hazards regression and generalized linear models controlled for patient/hospital confounders. RESULTS: Among the 65,067 patients identified, 30% underwent cholecystectomy. The NOM cohort was older (58 vs. 50 years), had more comorbidities (Charlson index > 2, 23.5% vs. 11.5%), fewer female patients (56.7% vs. 67%) and less discharge-to-home (84.9% vs. 94.4%) (all p < 0.001). NOM was associated with increase in recurrence and unplanned readmissions at 30d [Hazard Ratio 3.53 (95% CI 2.92-4.27), 2.41 (2.11-2.74), respectively], and 180d [4.27 (3.65-4.98), 2.78 (2.54-3.04), respectively], as well as increased mortality during 180d readmission 1.88 (1.06-3.35). This approach was also associated with significant increase in LOS [predicted mean difference 2.79 days (95% CI 2.46-3.12)] and total costs [$2507.89 ($1714.4-$3301.4)]. CONCLUSIONS: In the USA, most patients presenting with mild GP do not undergo same hospitalization cholecystectomy. This strategy results in higher recurrent pancreatitis, mortality during readmission, and an additional $4.85 M/year in hospital costs nationwide. These data support same hospitalization cholecystectomy as the gold standard for mild GP.

In Vitro and In Vivo Characterization of Tebipenem (TBP), an Orally Active Carbapenem, against Biothreat Pathogens.

Bacillus anthracis and Yersinia pestis, causative pathogens for anthrax and plague, respectively, along with Burkholderia mallei and B. pseudomallei are potential bioterrorism threats. Tebipenem pivoxil hydrobromide (TBP HBr, formerly SPR994), is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) gram-negative pathogens, including quinolone-resistant and extended-spectrum-ß-lactamase-producing Enterobacterales. We evaluated the in vitro activity and in vivo efficacy of tebipenem against biothreat pathogens. Tebipenem was active in vitro against 30-strain diversity sets of B. anthracis, Y. pestis, B. mallei, and B. pseudomallei with minimum inhibitory concentration (MIC) values of 0.001 - 0.008 µg/ml for B. anthracis, ≤0.0005 - 0.03 µg/ml for Y. pestis, 0.25 - 1 µg/ml for B. mallei, and 1 - 4 µg/ml for B. pseudomallei In a B. anthracis murine model, all control animals died within 52 h post challenge. The survival rates in the groups treated with tebipenem were 75% and 73% when dosed at 12 h and 24 h post challenge, respectively. The survival rates in the positive control groups treated with ciprofloxacin were 75% and when dosed 12 h and 25% when dosed 24 h post challenge, respectively. Survival rates were significantly (p=0.0009) greater in tebipenem groups treated at 12 h and 24 h post challenge and in the ciprofloxacin group 12 h post-challenge vs. the vehicle-control group. For Y. pestis, survival rates for all animals in the tebipenem and ciprofloxacin groups were significantly (p<0.0001) greater than the vehicle-control group. These results support further development of tebipenem for treating biothreat pathogens.

In Vitro and In Vivo Characterization of Tebipenem, an Oral Carbapenem.

The continued evolution of bacterial resistance to the ß-lactam class of antibiotics has necessitated countermeasures to ensure continued effectiveness in the treatment of infections caused by bacterial pathogens. One relatively successful approach has been the development of new ß-lactam analogs with advantages over prior compounds in this class. The carbapenems are an example of such ß-lactam analogs possessing improved stability against ß-lactamase enzymes and, therefore, a wider spectrum of activity. However, all carbapenems currently marketed for adult patients are intravenous agents, and there is an unmet need for an oral agent to treat patients that otherwise do not require hospitalization. Tebipenem pivoxil hydrobromide (tebipenem-PI-HBr or SPR994) is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) Gram-negative pathogens, including quinolone-resistant and extended-spectrum-ß-lactamase-producing Enterobacterales Tebipenem-PI-HBr is currently in development for the treatment of complicated urinary tract infections (cUTI). Microbiological data are presented here that demonstrate equivalency of tebipenem with intravenous carbapenems such as meropenem and support its use in infections in which the potency and spectrum of a carbapenem are desired. The results from standard in vitro microbiology assays as well as efficacy in several in vivo mouse infection models suggest that tebipenem-PI-HBr could be a valuable oral agent available to physicians for the treatment of infections, particularly those caused by antibiotic-resistant Gram-negative pathogens.

Patients support transfer of care for unexpected findings in laparoscopic cholecystectomy.

INTRODUCTION: Surgeons often assume patients may be dissatisfied if their operations were stopped due to suspicious intraoperative findings requiring transfer of care. We sought to assess patient opinions regarding transfer of care for unexpected intraoperative findings during laparoscopic cholecystectomy with and without bile duct injury (BDI). METHODS AND PROCEDURES: The investigators developed two clinical scenarios comparing transfer of care for unexpected intraoperative findings during elective laparoscopic cholecystectomy: without BDI and with BDI requiring open repair. A multi-institutional structured telephone interview process was conducted with patients ≥ 18 years of age who had an outpatient, uncomplicated laparoscopic cholecystectomy within the last year. The first scenario presented a case of suspicious findings prompting the surgeon to stop and transfer for specialized care; whereas the second case was a BDI requiring transfer of care. Textual and thematic analysis as well as descriptive statistics was used for analysis, with significance set at p < 0.05. RESULTS: Forty-five patients completed the survey. Satisfaction with transfer of care for unexpected intraoperative findings without BDI was 69%, and over 95% of respondents were satisfied their surgeon stopped the procedure to initiate transfer due to safety concerns; 64% of patients would return to that surgeon for postoperative care; and 78% would see that surgeon again. In the scenario with BDI requiring open repair, 86% were satisfied with their surgeon's decision to stop the operation; 91% of patients were satisfied with transfer of care; and 32% would see their first surgeon again. Themes of prioritizing safety and transparency were frequently cited. CONCLUSIONS: Patients prioritize safety and are satisfied with halting a procedure to facilitate transfer of care for suspicious intraoperative findings during routine laparoscopic cholecystectomy.

Achalasia and obesity: patient outcomes and impressions following laparoscopic Heller myotomy and Dor fundoplication.

PURPOSE: The optimal management of achalasia in obese patients is unclear. For those who have undergone Heller myotomy and fundoplication, the long-term outcomes and their impressions following surgery are largely unknown. METHODS: A retrospective review of patients who underwent laparoscopic Heller myotomy and Dor fundoplication (LHMDF) for achalasia was performed. From this cohort, Class 2 and 3 obese (BMI > 35 kg/m2) patients were identified for short- and long-term outcome analysis. RESULTS: Between 2003 and 2015, 252 patients underwent LHMDF for achalasia, and 17 (7%) patients had BMI > 35 kg/m2. Pre-operative Eckardt scores varied from 2 to 9, and at short-term (2-4 week) follow-up, scores were 0 or 1. Ten (58%) patients had available long-term (2-144 months) follow-up data. Eckardt scores at this time ranged from 0 to 6. Symptom recurrence was worse for patients with BMI > 40 kg/m2 compared to patients with BMI < 40 kg/m2. BMI was largely unchanged at long-term follow-up regardless of pre-intervention BMI. Most patients were satisfied with surgery but would have considered a combined LHMDF and weight-loss procedure had it been offered. CONCLUSION: LHMDF for achalasia in obese patients is safe and effective in the short term. At long-term follow-up, many patients had symptom recurrence and experienced minimal weight loss. Discussing weight-loss surgery at the time LHMDF may be appropriate to ensure long-term achalasia symptom relief.

Preoperative anemia: a common finding that predicts worse outcomes in patients undergoing primary hiatal hernia repair.

BACKGROUND: The increased incidence of anemia in patients with hiatal hernias (HH) and resolution of anemia after HH repair (HHR) have been clearly demonstrated. However, the implications of preoperative anemia on postoperative outcomes have not been well described. In this study, we aimed to identify the incidence of preoperative anemia in patients undergoing primary HHR at our institution and sought to determine whether preoperative anemia had an impact on postoperative outcomes. METHODS: Using our IRB-approved institutional HH database, we retrospectively identified patients undergoing primary HHR between January 2011 and April 2017 at our institution. We identified patients with anemia, defined as serum hemoglobin levels less than 13 mg/dL in men and 12 mg/dL in women, measured within two weeks prior to surgery, and compared this group to a cohort of patients with normal preoperative hemoglobin. Perioperative outcomes analyzed included estimated blood loss (EBL), operative time, perioperative blood transfusions, failed postoperative extubation, intensive care unit (ICU) admission, postoperative complications, length of stay (LOS), and 30-day readmission. Outcomes were compared by univariable and multivariable analyses, with significance set at p < 0.05. RESULTS: We identified 263 patients undergoing HHR. The median age was 66 years and most patients were female (78%, n = 206). Seventy patients (27%) were anemic. In unadjusted analyses, anemia was significantly associated with failed postoperative extubation (7 vs. 2%, p = 0.03), ICU admission (13 vs. 5%, p = 0.03), postoperative blood transfusions (9 vs. 0%, p < 0.01), and postoperative complications (41 vs. 18%, p < 0.01). On adjusted multivariable analysis, anemia was associated with 2.6-fold greater odds of postoperative complications (OR 2.57; 95% CI 1.36-4.86; p < 0.01). CONCLUSIONS: In this study, anemia had a prevalence of 27% in patients undergoing primary HHR. Anemic patients had 2.6-fold greater odds of developing postoperative complications. Anemia is common in patients undergoing primary HHR and warrants consideration for treatment prior to elective repair.

Assessment of the In Vivo Activity of SPR741 in Combination with Azithromycin against Multidrug-Resistant Enterobacteriaceae Isolates in the Neutropenic Murine Thigh Infection Model.

SPR741 is a novel agent with structural similarity to polymyxins that is capable of potentiating the activities of various classes of antibiotics. Previously published studies indicated that although Enterobacteriaceae isolates had minimal susceptibilities to azithromycin (AZM), the in vitro antimicrobial activity of AZM against Enterobacteriaceae was enhanced when it was combined with SPR741. The current study evaluated the in vivo activity of human-simulated regimens (HSR) of AZM equivalent to clinical doses of 500 mg given intravenously (i.v.) every 24 h (q24h) and SPR741 equivalent to clinical doses of 400 mg q8h i.v. (1-h infusion), alone and in combination, against multidrug-resistant (MDR) Enterobacteriaceae We studied 30 MDR Enterobacteriaceae isolates expressing a wide spectrum of ß-lactamases (ESBL, NDM, VIM, and KPC), including a subset of isolates positive for genes conferring macrolide resistance (mphA, mphE, ermB, and msr). In vivo activity was assessed as the change in log10 CFU per thigh at 24 h compared with 0 h. Treatment with AZM alone was associated with net growth of 2.60 ± 0.83 log10 CFU/thigh. Among isolates with AZM MICs of ≤16 mg/liter, treatment with AZM-SPR741was associated with an average reduction in bacterial burden of -0.53 ± 0.82 log10 CFU/thigh, and stasis to 1-log kill was observed in 9/11 isolates (81.8%). Combination therapy with an AZM-SPR741 HSR showed promising in vivo activity against MDR Enterobacteriaceae isolates with AZM MICs of ≤16 mg/liter, including those producing a variety of ß-lactamases. These data support a potential role for AZM-SPR741 in the treatment of infections due to MDR Enterobacteriaceae.

A standardized comparison of peri-operative complications after minimally invasive esophagectomy: Ivor Lewis versus McKeown.

BACKGROUND: While our institutional approach to esophageal resection for cancer has traditionally favored a minimally invasive (MI) 3-hole, McKeown esophagectomy (MIE 3-hole) during the last five years several factors has determined a shift in our practice with an increasing number of minimally invasive Ivor Lewis (MIE IL) resections being performed. We compared peri-operative outcomes of the two procedures, hypothesizing that MIE IL would be less morbid in the peri-operative setting compared to MIE 3-hole. METHODS: Our institution's IRB-approved esophageal database was queried to identify all patients who underwent totally MI esophagectomy (MIE IL vs. MIE 3-hole) from June 2011 to May 2016. Patient demographics, preoperative and peri-operative data, as well as post-operative complications were compared between the two groups. Post-operative complications were analyzed using the Clavien-Dindo classification system. RESULTS: There were 110 patients who underwent totally MI esophagectomy (MIE IL n = 49 [45%], MIE 3-hole n = 61 [55%]). The majority of patients were men (n = 91, 83%) with a median age of 62.5 (range 31-83). Preoperative risk stratifiers such as ECOG score, ASA, and Charlson Comorbidity Index were not significantly different between groups. Anastomotic leak rate was 2.0% in the MIE IL group compared to 6.6% in the MIE 3-hole group (p = 0.379). The rate of serious (Clavien-Dindo 3, 4, or 5) post-operative complications was significantly less in the MIE IL group (34.7 vs. 59.0%, p = 0.013). Serious pulmonary complications were not significantly different (16.3 vs. 26.2%, p = 0.251) between the two groups. CONCLUSIONS: In this cohort, totally MIE IL showed significantly less severe peri-operative morbidity than MIE 3-hole, but similar rates of serious pulmonary complications and anastomotic leaks. These findings confirm the safety of minimally invasive Ivor Lewis esophagectomies for esophageal cancer when oncologically and clinically appropriate. Minimally invasive McKeown esophagectomy remains a satisfactory and appropriate option when clinically indicated.

SPR741, an Antibiotic Adjuvant, Potentiates the In Vitro and In Vivo Activity of Rifampin against Clinically Relevant Extensively Drug-Resistant Acinetobacter baumannii.

Acinetobacter baumannii is responsible for 10% of all nosocomial infections and has >50% mortality rates when causing ventilator-associated pneumonia. In this proof-of-concept study, we evaluated SPR741, an antibiotic adjuvant that permeabilizes the Gram-negative membrane, in combination with rifampin against AB5075, an extensively drug-resistant (XDR) A. baumannii strain. In standard in vitro assays and in a murine pulmonary model, we found that this drug combination can significantly reduce bacterial burden and promote animal survival despite an aggressive infection.

Total parenteral nutrition in patients following pancreaticoduodenectomy: lessons from 1184 patients.

BACKGROUND: Total parenteral nutrition (TPN) has historically been used conservatively in the management of patients after pancreaticoduodenectomy (PD). Herein, we evaluate the indications for and outcomes associated with TPN use in a high-volume pancreatic surgery center. MATERIALS AND METHODS: We retrospectively queried our institution's pancreatic surgery database for patients who received TPN after PD from 2006 through 2015. RESULTS: Of 1184 patients who underwent PD, 232 (19.6%) received TPN perioperatively. The most common indications for TPN were delayed gastric emptying (DGE, n = 171, 73.7%), pancreatic fistula (n = 102, 44%), and generalized malnutrition (n = 25, 10.8%). The median day of TPN initiation was postoperative day 4 (range: -31 to 22), with a median usage of 9 days (range: 1-115). Forty-four (19%) patients received short-course TPN (≤3 days), primarily those diagnosed with isolated grade A DGE without associated complications (P = 0.0003). Multivariate analysis suggests the presence of deep surgical site infection (odds ratio: 3.09, [1.16-5.06], P = 0.018) or pancreatic fistula (odds ratio: 2.57, [1.03-6.41], P = 0.043) at the time of DGE presentation as predictive of long-term TPN requirement. Hyperglycemia (34.5%) was the most common complication resulting from TPN use, whereas central line-associated bloodstream infections (2.6%) were rare. Readmissions (35.3% TPN cohort; 15% historical institutional rate) were most commonly due to poor oral intake (26.8%). The 30-day mortality rate in the overall TPN cohort was 3.4% (0.8% historical institutional rate). CONCLUSIONS: TPN is a critical and safe adjunct for patients who develop PD-associated complications; however, it may be of limited utility for patients with isolated DGE.

Increasing resident utilization and recognition of the critical view of safety during laparoscopic cholecystectomy: a pilot study from an academic medical center.

BACKGROUND: Laparoscopic cholecystectomy (LC) is a commonly performed surgical procedure; however, it is associated with an increased rate of bile duct injury (BDI) when compared to the open approach. The critical view of safety (CVS) provides a secure method of ductal identification to help avoid BDI. CVS is not universally utilized by practicing surgeons and/or taught to surgical residents. We aimed to pilot a safe cholecystectomy curriculum to demonstrate that educational interventions could improve resident adherence to and recognition of the CVS during LC. METHODS: Forty-three general surgery residents at Thomas Jefferson University Hospital were prospectively studied. Fifty-one consecutive LC cases were recorded during the pre-intervention period, while the residents were blinded to the outcome measured (CVS score). As an intervention, a comprehensive lecture on safe cholecystectomy was given to all residents. Fifty consecutive LC cases were recorded post-intervention, while the residents were empowered to "time-out" and document the CVS with a doublet photograph. Two independent surgeons scored the videos and photographs using a 6-point scale. Residents were surveyed pre- and post-intervention to determine objective knowledge and self-reported comfort using a 5-point Likert scale. RESULTS: In the 18-week study period, 101 consecutive LCs were adequately captured and included (51 pre-intervention, 50 post-intervention). Patient demographics and clinical data were similar. The mean CVS score improved from 2.3 to 4.3 (p < 0.001). The number of videos with CVS score >4 increased from 15.7 to 52 % (p < 0.001). There was strong inter-observer agreement between reviewers. The pre- and post-intervention questionnaire response rates were 90.7 and 83.7 %, respectively. A greater number of residents correctly identified all criteria of the CVS post-intervention (41-93 %, p < 0.001) and offered appropriate bailout techniques (77-94 %, p < 0.001). Residents strongly agreed that the CVS education should be included in general surgery residency curriculum (mean Likert score = 4.71, SD = 0.54). Residents also agreed that they are more comfortable with their LC skills after the intervention (4.27, σ = 0.83). CONCLUSION: The combination of focused education along with intraoperative time-out significantly improved CVS scores and knowledge during LC in our institution.

Surgical approaches to adenocarcinoma of the gastroesophageal junction: the Siewert II conundrum.

BACKGROUND: The Siewert classification system for gastroesophageal junction adenocarcinoma has provided morphological and topographical information to help guide surgical decision-making. Evidence has shown that Siewert I and III tumors are distinct entities with differing epidemiologic and histologic characteristics and distinct patterns of disease progression, requiring different treatment. Siewert II tumors share some of the characteristics of type I and III lesions, and the surgical approach is not universally agreed upon. Appropriate surgical options include transthoracic esophagogastrectomy, transhiatal esophagectomy, and transabdominal extended total gastrectomy. PURPOSE: A review of the available evidence of the surgical management of Siewert II tumors is presented. CONCLUSIONS: Careful review of the data appear to support the fact that a satisfactory oncologic resection can be achieved via a transabdominal extended total gastrectomy with a slight advantage in terms of perioperative complications, and overall postoperative quality of life. Overall and disease-free survival compares favorably to the transthoracic approach. These results can be achieved with careful selection of patients balancing more than just the Siewert type in the decision-making but considering also preoperative T and N stages, histological type (diffuse type requiring longer margins that are not always achievable via gastrectomy), and the presence of Barrett's esophagus.

Long-term functional outcomes of laparoscopic resection for gastric gastrointestinal stromal tumors.

INTRODUCTION: Laparoscopic resection is rapidly becoming the treatment of choice for small- to medium-sized gastric gastrointestinal stromal tumors (GIST). While long-term oncologic data are available, quality of life outcomes are less known. METHODS: Our IRB-approved prospectively maintained database was retrospectively queried (2003-2013) for patients who underwent laparoscopic gastric GIST resection. Demographics along with perioperative and oncologic outcomes were collected and analyzed. Patients were contacted and asked to complete a quality of life survey consisting of Likert scales scored from 1 to 5. Patients also completed the Gastrointestinal Quality of Life Index (GIQLI). RESULTS: A total of 69 patients were identified and 36 patients (59.0% of eligible patients) responded to the survey. Median follow-up was 39 months. Patients most commonly reported no change in weight, appetite, early satiety, heartburn, persistent cough, dysphagia, and reflux medication dosing postoperatively. The median scores for chest pain and regurgitation were 4, falling in the "worsened" range. 8.33% of patients reported worsened chest pain and 11.11% of patients reported worsened regurgitation postoperatively. The GIQLI scores had a mean of 126.9 (range 77-141). CONCLUSION: While some patients reported a worsening in early satiety, most patients reported no change in symptoms postoperatively, and the GIQLI scores remained within the normal range. Laparoscopic resection of gastric GIST provides durable results with minimal effect on longer-term quality of life.

Bimatoprost 0.03% for the Treatment of Eyebrow Hypotrichosis.

BACKGROUND: Eyebrow loss may have substantial negative functional and social consequences. OBJECTIVE: Evaluate the safety and efficacy of bimatoprost 0.03% in subjects with eyebrow hypotrichosis. METHODS: This multicenter, double-masked study randomized adult females or males with eyebrow hypotrichosis to receive bimatoprost 0.03% twice (BID) or once daily (QD) or vehicle BID for 7 months. Primary endpoint was overall eyebrow fullness at Month 7. Secondary endpoints included eyebrow fullness (mm), darkness (intensity units), and subject satisfaction with treatment. Safety was also assessed. RESULTS: At Month 7, the proportion of subjects with improvement was significantly higher in bimatoprost groups versus vehicle (both, p < .001). Improvements occurred in both bimatoprost groups versus vehicle after Month 1 and continued through follow-up; eyebrow fullness and darkness improved as early as Months 2 and 1, respectively (both, p < .001). Greater satisfaction was reported with bimatoprost versus vehicle at Month 2 and all subsequent time points. Overall, 38.1%, 42.4%, and 35.5% of subjects in the bimatoprost BID, QD, and vehicle groups, respectively, experienced ≥1 treatment-emergent adverse event (TEAE). Most frequent TEAEs were similar across groups. No skin or iris hyperpigmentation or conjunctival hyperemia occurred. CONCLUSION: Bimatoprost 0.03% BID and QD is safe, well tolerated, and effective for eyebrow hypotrichosis.

A Comprehensive Approach to Multimodal Facial Aesthetic Treatment: Injection Techniques and Treatment Characteristics From the HARMONY Study.

BACKGROUND: The HARMONY study is the first clinical trial to assess the impact of a global approach to facial rejuvenation with several minimally invasive modalities, using patient-reported outcome measures. OBJECTIVE: Provide details of this treatment approach and describe investigators' experiences and recommendations based on this study. METHODS: This multicenter, 4-month study evaluated subject satisfaction with and psychological impact of combined treatment with VYC-20L (Juvéderm Voluma XC), HYC-24L (Juvéderm Ultra XC), HYC-24L+ (Juvéderm Ultra Plus XC), onabotulinumtoxinA (Botox), and bimatoprost 0.3% ophthalmic solution (Latisse). Treatment-naive adults with moderate-to-severe facial lines and folds and eyelash hypotrichosis received on-label, staged treatment with fillers. Bimatoprost was self-administered once daily for 17 weeks from day 1. OnabotulinumtoxinA was administered for glabellar lines, crow's feet lines, or both at month 3. RESULTS: Overall, 100 subjects received bimatoprost for eyelash hypotrichosis, 96 received onabotulinumtoxinA for glabellar lines and/or crow's feet lines, and 96 received VYC-20L for midface volume deficit. From 17 to 96 subjects received HYC-24L and/or HYC-24L+ for nasolabial folds, oral commissures, marionette lines, perioral lines, or radial cheek lines. Injections of filler generally progressed from cranial to caudal, with midface injected first. Investigator-reported factors that may have contributed to the potential benefits of this approach include the critical role of the midface in facial aesthetics, use of lower volumes of filler in individual facial areas, and anesthetic effects. CONCLUSION: The investigators' perspectives and experience with the injection pattern, sequencing, volumes, and techniques may provide valuable guidance for a multimodal approach to facial aesthetic treatment.

Characterization of a novel small molecule that potentiates ß-lactam activity against gram-positive and gram-negative pathogens.

In a loss-of-viability screen using small molecules against methicillin-resistant Staphylococcus aureus (MRSA) strain USA300 with a sub-MIC of a ß-lactam, we found a small molecule, designated DNAC-1, which potentiated the effect of oxacillin (i.e., the MIC of oxacillin decreased from 64 to 0.25 µg/ml). Fluorescence microscopy indicated a disruption in the membrane structures within 15 min of exposure to DNAC-1 at 2× MIC. This permeabilization was accompanied by a rapid loss of membrane potential, as monitored by use of the DiOC2 (3,3'-diethyloxacarbocyanine iodide) dye. Macromolecular analysis showed the inhibition of staphylococcal cell wall synthesis by DNAC-1. Transmission electron microscopy of treated MRSA USA300 cells revealed a slightly thicker cell wall, together with mesosome-like projections into the cytosol. The exposure of USA300 cells to DNAC-1 was associated with the mislocalization of FtsZ accompanied by the localization of penicillin-binding protein 2 (PBP2) and PBP4 away from the septum, as well as mild activation of the vraRS-mediated cell wall stress response. However, DNAC-1 does not have any generalized toxicity toward mammalian host cells. DNAC-1 in combination with ceftriaxone is also effective against an assortment of Gram-negative pathogens. Using a murine subcutaneous coinjection model with 10(8) CFU of USA300 as a challenge inoculum, DNAC-1 alone or DNAC-1 with a sub-MIC of oxacillin resulted in a 6-log reduction in bacterial load and decreased abscess formation compared to the untreated control. We propose that DNAC-1, by exerting a bimodal effect on the cell membrane and cell wall, is a viable candidate in the development of combination therapy against many common bacterial pathogens.