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Background. We have previously shown that vancomycin-resistant E. faecium (VRE) with DAP MICs close to the breakpoint (4 mug/mL) harbor genetic changes associated with DAP resistance (DAP-R). Further, DAP MIC was a predictor of poor microbiological eradication in patients with VRE bacteremia treated with DAP. Furthermore, DAP-susceptible VRE isolates with DAP MIC of 3-4 mug/mL (Etest) were more likely to fail DAP therapy, independently of the DAP dose used. Here, we used WGS to determine whether mutations associated with DAP-R could predict DAP MICs. Methods. We performed WGS to identify potential determinants of DAP-R in 80 E. faecium isolates (62 DAP-S and 18 DAP-R recovered from bloodstream and other infection sites) in diverse US geographical locations. Two modeling strategies were employed with the aim of increasing the robustness of our prediction strategy, (i) a logistic regression model approach to predict the probability of an isolate of exhibiting a DAP MIC of >= 3mug/dl based on the presence of relevant mutations, and (ii) a linear regression model to predict a single doubling dilution increase on DAP MIC in the presence or absence of mutations associated with DAP-R, after transforming MICs to a log2 scale. Statistical significance (P value) was set at <0.05. Results. Out of 62 genetic determinants examined, the presence of substitutions in LiaFSR or YycFGHI systems were independent predictors of an isolate exhibiting DAP MIC >= 3 mug/mL (logistic model, LiaFSR OR 8.9, P < 0.0001 and YycFGHI OR 6.2; P < 0.0001) or of an increase in DAP MIC (lineal model; LiaFSR beta 14.6; P < 0.04; YycFGHI beta 1.7; P < 0.0001) and were consistent in both models. When we evaluated individual genetic changes within the proteins from both systems, substitutions in YycG were associated with the greatest increase on DAP MIC (8.0-fold; beta = 3.0, 95% CI 2.8-4.1 P < 0.0001), followed by LiaF (3.0-fold; beta 1.5, 95% CI 0.17-2.9 P = 0.028;), LiaS (2.0-fold; beta = 0.9, 95% CI 0.2-1.6; P = 0.006) and LiaR (1.7-fold; beta = 0.8, 95% CI 0.1-1.5, P = 0.021). Conclusion. Our data indicate that WGS may identify organisms with elevated DAP MIC that, even if not above the clinical breakpoint, may lead to microbiological failure. WGS has the potential of providing a better guidance for DAP therapy

One to two percent of ectopic parathyroid adenomas are found in the lower mediastinum and often these are best accessed via a sternotomy or thoracotomy. Video-assisted thoracoscopic surgery (VATS) is an alternative approach with less surgical trauma, decreased morbidity, shorter hospital stays, and superior cosmetic results. Ten years after the first VATS resection of an ectopic mediastinal parathyroid, a robot-assisted thoracoscopic approach was described. Here we describe a series of five robot assisted complete thymectomies in patients with primary hyperparathyroidism due to mediastinal ectopic parathyroid adenomas. A single surgeon, single institution case series of five consecutive robotic-assisted mediastinal parathyroidectomies was performed between March 2013 and September 2015. The patients' ages ranged from 31 to 65, 80 % were female, and all had primary hyperparathyroidism due to an ectopic parathyroid located in the lower mediastinum. Pre-operative imaging workup included Technetium 99-sestimibi parathyroid scan and CT scan of the chest. An ectopic parathyroid adenoma was successfully removed in all five cases, with intraoperative iOPTH decreasing ~50 % from baseline after 10 minutes. A hypercellular parathyroid was confirmed on pathologic exam in all specimens. Post-operative discharge and follow up calcium levels all returned to normal. There were no intraoperative complications, including no recurrent laryngeal nerve injuries, no postoperative morbidity, and no mortalities. This case series demonstrates that a robot-assisted complete thymectomy for mediastinal parathyroid adenomas causing primary hyperparathyroidism provides excellent visualization of the mediastinum, is effective at reducing PTH and calcium levels, and is safe with no morbidity or mortality.

BACKGROUND:: A recently available, low profile, fully covered metal stent with symmetrical flares (FCMSF) may offer improved resistance to migration in esophageal disease. MATERIALS AND METHODS:: A retrospective review of 58 esophageal FCMSF placed in 46 consecutive patients was performed. Pathologies included stricture and leak of benign and malignant etiology. RESULTS:: Sixteen of 58 stents (28%) were placed urgently/emergently. All patients had successful stent deployment with 0% stent-related hospital mortality. Postoperative morbidity occurred in 15 of the 58 (26%) stents and included stent migration, atrial fibrillation, pneumonia, pneumothorax, urinary retention, hemodynamic instability, and chronic obstructive pulmonary disease exacerbation. In patients with stricture (n=29), mean dysphagia scores were reduced from 3.1+/-0.6 preoperatively to 1.1+/-0.8 postoperatively (P<0.001). For leak, stent therapy (+/-drainage) avoided formal esophageal operation in 95% (21/22). Four stents (6.9%) were removed for stent migration, 2 of which migrated after adjuvant chemoradiation. Adjuvant chemoradiation therapy was an independent risk factor for stent migration (odds ratio=1.6; P=0.02) by multivariable regression analysis. The mean duration of stent therapy was 65+/-62 days for stricture (27/34 remain in situ) and 57+/-57 days for leak (10/22 remain in situ). The median hospital length of stay was 2 days. CONCLUSIONS:: FCMSF provide a safe and effective therapy for both benign and malignant esophageal dysphagia and leaks. The symmetrical property may contribute to the overall low observed migration rate while still allowing for simple and safe stent retrieval.