Citations

AbstractThe combination of pomalidomide (POM) and dexamethasone (DEX) was evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL) and primary vitreoretinal lymphoma (PVRL) to determine the maximal tolerated dose (MTD) of POM as the primary objective, and overall response rate (ORR), progression-free survival (PFS), and safety profile as secondary objectives. A cohorts-of-3 study design was used with a dose-escalation schedule consisting of POM (3, 5, 7, or 10 mg) orally daily for 21 days every 28 days and DEX 40 mg orally every week. After 2 cycles, POM was continued alone until disease progression, intolerance, or subject withdrawal. Following MTD determination, the MTD cohort was expanded. Twenty-five of 29 patients with the median of 3 prior treatments were eligible for assessment as per international PCNSL collaborative group criteria. The MTD of POM was 5 mg daily for 21 days every 28 days. Whole-study ORR was 48% (12 of 25; 95% confidence interval [CI], 27.8%, 68.7%) with 6 complete response (CR), 2 complete response, unconfirmed (CRu), and 4 partial response (PR). MTD cohort ORR was 50% (8 of 16; 95% CI, 24.7%, 75.4%) with 5 CR, 1 CRu, and 2 PR. Median PFS was 5.3 months (whole study) and 9 months (for responders). One patient had pseudoprogression. Grade 3/4 hematologic toxicities included neutropenia (21%), anemia (8%), and thrombocytopenia (8%). Grade 3/4 nonhematologic toxicities included lung infection (12%), sepsis (4%), fatigue (8%), syncope (4%), dyspnea (4%), hypoxia (4%), respiratory failure (8%), and rash (4%). POM/DEX treatment is feasible with significant therapeutic activity against relapsed/refractory PCNSL and PVRL. This trial was registered at www.clinicaltrials.gov as #NCT01722305.

Abstract: The observation of decreased resident autonomy, ultimately influencing the readiness of a new graduate to practice, has been supported with a number of recent surveys. This perceived lack of autonomy is felt to be due, in part, to many reasons, including duty-hour regulations, increased supervision requirements, patient safety measures, concern for complication rates, and other performance measures. Pressure on faculty members to have increased clinical productivity may not allow for more resident autonomy. Increased clinical exposure to improve resident independence may come from several suggested areas. First, restructuring the residency program to allow for more clinical time may be one way to improve education. Second, increased use of surgical simulation will allow for more experience to develop technical skills within a controlled environment. Surgical simulators can be used to acquire new skills and also as a means of assessing competence. Third, competency-based education (CBE) has been offered as a way to improve resident education. At its core, CBE offers criterion-based assessments for residents and faculty that allow for more frequent feedback.

Objective: With advancements in surgical equipment and procedures, human–system interactions in operating rooms affect surgeon workload and performance. Workload was measured across surgical specialties using surveys to identify potential predictors of high workload for future performance improvement. Summary Background Data: Surgical instrumentation and technique advancements have implications for surgeon workload and human–systems interactions. To understand and improve the interaction of components in the work system, NASA-Task Load Index can measure workload across various fields. Baseline workload measurements provide a broad overview of the field and identify areas most in need of improvement. Methods: Surgeons were administered a modified NASA-Task Load Index survey (0 = low, 20 = high) following each procedure. Patient and procedural factors were retrieved retrospectively. Results: Thirty-four surgeons (41% female) completed 662 surgery surveys (M = 14.85, SD = 7.94), of which 506 (76%) have associated patient and procedural data. Mental demand (M = 7.7, SD = 5.56), physical demand (M = 7.0, SD = 5.66), and effort (M = 7.8, SD = 5.77) were the highest rated workload subscales. Surgeons reported difficulty levels higher than expected for 22% of procedures, during which workload was significantly higher ( P < 0.05) and procedural durations were significantly longer ( P > 0.001). Surgeons reported poorer perceived performance during cases with unexpectedly high difficulty ( P < 0.001). Conclusions: When procedural difficulty is greater than expected, there are negative implications for mental and physical demand that result in poorer perceived performance. Investigations are underway to identify patient and surgical variables associated with unexpected difficulty and high workload. Future efforts will focus on re-engineering the surgical planning process and procedural environment to optimize workload and performance for improved surgical care.

Abstract Background Reflux phenotypes have classically been divided into supine, upright, and bipositional predominant reflux. Recent data on clinical, endoscopic, and manometric features in these patient groups are scant and most prior reports occurred prior to the advent of high resolution impedance manometry and prolonged wireless pH monitoring. We aimed to evaluate the distribution, demographic, manometric, and endoscopic characteristics of the reflux phenotypes in this modern era of testing. Methods Patients who had esophageal physiology testing at a single tertiary care center over a one year period were retrospectively reviewed for demographic, clinical, endoscopic, manometric and pH impedance data. We included consecutive patients who had undergone pH-impedance or wireless pH testing with an EGD within 6 months. Results 139 patients were included and 91 (65.5%) patients were women was mean age of 51.9 + /- 15.2 years and mean BMI of 29.1 + /- 6.4. The most common reflux pattern was bipositional (46% of patients), followed by supine (25%). Baseline characteristics, endoscopic and manometric data across groups are included in Table 1. Barrett's esophagus was most common in the non-acid group. Endoscopically, esophagitis was most common in the supine and bipositional groups. Manometric findings were similar across groups. Conclusion The epidemiology of GERD patients appears to be changing as evidenced by a higher mean BMI than in the largest prior study from 1999. Despite demographic changes in GERD and more widespread use of advanced esophageal physiology testing, the manometric and endoscopic characteristics of GERD phenotypes remains fairly similar. Disclosure All authors have declared no conflicts of interest.

Abstract Rationale Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC). Objectives To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Methods Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite at least 6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS + GBT) or GBT alone. Once-daily ALIS was supplied in single-use vials delivering 590 mg amikacin to the nebulizer. The primary endpoint was culture conversion, defined as three consecutive monthly MAC-negative sputum cultures by Month 6. Measurements and Main Results Enrolled patients (ALIS + GBT, n = 224; GBT-alone, n = 112) were a mean 64.7 years old and 69.3% female. Most had underlying bronchiectasis (62.5%), chronic obstructive pulmonary disease (14.3%), or both (11.9%). Culture conversion was achieved by 65 of 224 patients (29.0%) with ALIS + GBT and 10 of 112 (8.9%) with GBT alone (odds ratio, 4.22; 95% confidence interval, 2.08–8.57; P &lt; 0.001). Patients in the ALIS + GBT arm versus GBT alone were more likely to achieve conversion (hazard ratio, 3.90; 95% confidence interval, 2.00–7.60). Respiratory adverse events (primarily dysphonia, cough, and dyspnea) were reported in 87.4% of patients receiving ALIS + GBT and 50.0% receiving GBT alone; serious treatment-emergent adverse events occurred in 20.2% and 17.9% of patients, respectively. Conclusions Addition of ALIS to GBT for treatment-refractory MAC lung disease achieved significantly greater culture conversion by Month 6 than GBT alone, with comparable rates of serious adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT02344004).