Citations

ABSTRACTWe are developing electrical approaches to treat biofilm‐associated orthopedic foreign‐body infection. Although we have previously shown that such approaches have antibiofilm activity, the effects on bone have not been assessed. Herein, low‐amperage 200 μA fixed direct current (DC) was compared with no current, in a rat femoral foreign‐body infection model. In the infected group, a platinum implant seeded with S. epidermidis biofilm (105 CFU/cm2), plus 50 μL of a 109 CFU suspension of bacteria, were placed in the femoral medullary cavity of 71 rats. One week later, rats were assigned to one of four groups: infected with no current or DC, or uninfected with no current or DC. After 2 weeks, bones were removed and subjected to histopathology, micro‐computed tomography (μCT), and strength testing. Histopathology showed no inflammation or bony changes/remodeling in the uninfected no current group, and some osteoid formation in the DC group; bones from the infected no current group had evidence of inflammation without bony changes/remodeling; along with inflammation, there was moderate osteoid present in the DC group. μCT showed more cortical bone volume and density, trabecular thickness, and cancellous bone volume in the DC group compared with the no current group, for both uninfected and infected bones (p < 0.05). There was no difference in torsional strength or stiffness between the no current versus DC groups, for both infected and uninfected bones (p > 0.05). © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Purpose: To examine the feasibility of a brief mindfulness intervention and to reduce nurse stress and burnout in an inpatient medical unit. Design: Single-arm, pre/post test study design. Method: Perceived Stress Scale (PSS), Maslach Burnout Inventory (MBI), and pre/post demographic questionnaires given at pre-intervention (baseline) and 6 weeks post-intervention. Intervention effectiveness was compared between the pre-survey ( N = 52) and post-survey ( N = 33). Five choices were offered to inpatient staff: a guided mindfulness CD, soothing sounds machine with a breathing technique instructional, mindfulness prompts, a journal, and water/snacks during six consecutive weekends. Findings: The mean PSS score did not improve and demonstrated a slight increase during the six-weekend intervention. However, mean MBI scores for the subscales of emotional exhaustion and depersonalization did demonstrate improvement as evident by decreased scores. Additionally, the mean MBI score for the subscale of personal accomplishment also improved with increased scores. Qualitative themes were positive and included relaxation, nourishment, and refocus. Majority of participants (75%) perceived the intervention as being effective or very effective in reducing stress at work. Respondents were “interested” or “very interested” in continuing a similar intervention in the future (84.9%). Conclusion: The improvement in scores for the MBI measures were a positive finding. The intervention was low cost, individualized, and accessible. The feasibility and perceptions of the intervention’s effectiveness has positive implications for the well-being of nurses.

Understanding which antimicrobial agents are likely to be active against Gram-negative bacilli can guide selection of antimicrobials for empirical therapy as mechanistic rapid diagnostics are adopted. In this study, we determined the MICs of a novel β-lactam–β-lactamase inhibitor combination, imipenem-relebactam, along with ceftolozane-tazobactam, imipenem, ertapenem, meropenem, ceftriaxone, and cefepime, against 282 drug-resistant isolates of Gram-negative bacilli.

PurposeThe purpose of this study was to determine clinically relevant pass/question/fail criteria for gamma analysis of intensity‐modulated radiation therapy quality assurance (IMRT QA) plans, identify which plans should be further analyzed with dose–volume histogram (DVH) metrics, and create a workflow for performing that DVH‐based analysis.MethodsA total of 11 plans, 5 prostate and 6 head/neck, were selected to represent known good plans based on their high‐passing rate using conventional IMRT QA criteria. These were modified by moving the programmed MLC positions to underdose the target or overdose important structures by varying amounts. Commercially available hardware/software was used to measure and analyze all plans (76 total) using 4%/3 mm, 3%/3 mm, 3%/2 mm, and 2%/2 mm gamma criteria. Two receiver operator characteristic (ROC) curves per criterion were created to assess effective passing rates. One ROC curve was to find a higher threshold that determined a clear pass and the second to find a lower threshold to determine a clear failure. Plans between these two thresholds need DVH‐based analysis to assess the clinical consequence of the dose difference. The modified plans were analyzed in the planning system and reconstructed in commercially available DVH‐based analysis software to access the accuracy and usefulness of the software.ResultsAnalysis of the ROC curves showed optimal pass and fail thresholds for plan error detection per criterion to achieve clinically relevant sensitivity and specificity. Based on measurement uncertainty and pass/fail ranges, 3%/2 mm gamma criteria with a pass threshold of 95% and a fail threshold of 90% were most optimal. DVH analysis showed good agreement with all reconstructed plans except where the changes to the MLC patterns caused the periphery of the target to be underdosed. For questionable plans, comparing the organ‐specific DVHs to the physician‐provided planning constraints proved to be an efficient and effective workflow since plans for which the target dose was slightly high or where organs at risk were underdosed could be released for the treatment without consulting the physician for a clinical decision.ConclusionThis work indicates the potential for appreciable improvement in error detection for IMRT QA. Using effective pass/fail thresholds to determine plans that need DVH‐based analysis minimizes the need for excessive, time‐consuming, analysis, and making use of the dosimetric constraints of the plan minimizes the burden on physicians. Overall, DVH‐based analysis is a powerful tool that can provide substantial insight over the traditional approach that does not provide structure‐specific data.

Purpose Selinexor, a first-in-class, oral, selective exportin 1 (XPO1) inhibitor, induces apoptosis in cancer cells through nuclear retention of tumor suppressor proteins and the glucocorticoid receptor, along with inhibition of translation of oncoprotein mRNAs. We studied selinexor in combination with low-dose dexamethasone in patients with multiple myeloma refractory to the most active available agents. Patients and Methods This phase II trial evaluated selinexor 80 mg and dexamethasone 20 mg, both orally and twice weekly, in patients with myeloma refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide (quad-refractory disease), with a subset also refractory to an anti-CD38 antibody (penta-refractory disease). The primary end point was overall response rate (ORR). Results Of 79 patients, 48 had quad-refractory and 31 had penta-refractory myeloma. Patients had received a median of seven prior regimens. The ORR was 21% and was similar for patients with quad-refractory (21%) and penta-refractory (20%) disease. Among patients with high-risk cytogenetics, including t(4;14), t(14;16), and del(17p), the ORR was 35% (six of 17 patients). The median duration of response was 5 months, and 65% of responding patients were alive at 12 months. The most common grade ≥ 3 adverse events were thrombocytopenia (59%), anemia (28%), neutropenia (23%), hyponatremia (22%), leukopenia (15%), and fatigue (15%). Dose interruptions for adverse events occurred in 41 patients (52%), dose reductions occurred in 29 patients (37%), and treatment discontinuation occurred in 14 patients (18%). Conclusion The combination of selinexor and dexamethasone has an ORR of 21% in patients with heavily pretreated, refractory myeloma with limited therapeutic options.