Methicillin-Resistant Staphylococcus aureus Bacteremia Treated With Vancomycin Calculated by Area-Under-the-Curve in Patients With Elevated Vancomycin Minimum Inhibitory Concentrations.

Purpose: Vancomycin is recommended as first-line treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, dosed by area-under-the-curve (AUC) with an assumed minimum inhibitory concentration (MIC) of 1 mcg/mL via broth microdilution. The purpose of this study was to compare effectiveness of AUC-based and trough-based dosing in MRSA bacteremia with an MIC > 1 mcg/mL via Etest. Methods: This was a retrospective, observational cohort that compared vancomycin dosed by AUC or trough between January 1, 2017 and September 1, 2022. The primary outcome was a composite of treatment failure defined as peristent bacteremia ≥ 7 days, inpatient mortality within 90 days, or microbiologic relapse or readmission within 30 days. Secondary outcomes compared nephrotoxicity, hospital and ICU length of stay, MIC differences, and difference in exposure measured by AUC. Results: Twenty-four patients in each group met inclusion criteria. For the primary outcome, there was no statistical difference in treatment failure between trough and AUC groups, respectively [10 (41.7%) vs 10 (41.7%), P = 1.000]. There was no statistical difference in secondary outcomes, with incidence of nephrotoxicity [3 (12.5%) trough vs 2 (8.33%) AUC, P = 1.000] and median AUC exposure over treatment course [502.9 mcg.h/mL (454.1-599.9) vs 474 mcg.h/mL (435.3-533), P = .312] similar between groups. Conclusion: There was no statistically significant difference in treatment failure for vancomycin by AUC or trough with an Etest MIC > 1 mcg/mL. Overall exposure to vancomycin and incidence of nephrotoxicty were numerically higher in the trough group, suggesting that dosing by AUC may limit exposure without impact on treatment failure.

Breast Cancer-Related Lymphedema (BCRL) and Bioimpedance Spectroscopy: Long-Term Follow-Up, Surveillance Recommendations, and Multidisciplinary Risk Factors.

BACKGROUND: Early detection and intervention for breast cancer-related lymphedema (BCRL) significantly decreases progression to persistent BCRL (pBCRL). We aimed to provide long-term follow-up on our early detection with bioimpedance spectroscopy (BIS) and early home intervention demonstrating reduced pBCRL to guide surveillance recommendations. PATIENTS AND METHODS: In total, 148 female patients with breast cancer who had axillary lymph node dissection (ALND) from November 2014 to December 2017 were analyzed. Baseline BIS measurements and postoperative follow-up occurred every 3 months for 1 year, biannual for 1 year, and then annually. An elevated BIS triggered evaluation and initiation of at-home interventions with reassessment for resolution versus persistent BCRL (pBCRL). High-risk factors and timing were analyzed. RESULTS: Mean follow-up was 55 months, and 65 (44%) patients had an abnormal BIS. Of these, 54 (82%) resolved with home intervention. The overall pBCRL rate was 8%. Average time to first abnormal BIS was 11.7 months. None of the stage 0 patients (0/34) and only 5/25 (20%) of stage 1 patients had pBCRL. All of stage 2 and stage 3 patients (7/7) had pBCRL. pBCRL correlated with number of positive nodes, percentage of positive nodes, stage of lymphedema at diagnosis, and recurring abnormal BIS measurements (p < 0.05). CONCLUSIONS: We have shown that patients undergoing ALND with early BCRL identified by BIS who performed home interventions had an 8% pBCRL rate. Patients at high risk for pBCRL should have routine surveillance starting at 9 months postoperatively to identify an opportunity for early intervention.

Mouse-INtraDuctal (MIND): an in vivo model for studying the underlying mechanisms of DCIS malignancy.

Due to widespread adoption of screening mammography, there has been a significant increase in new diagnoses of ductal carcinoma in situ (DCIS). However, DCIS prognosis remains unclear. To address this gap, we developed an in vivo model, Mouse-INtraDuctal (MIND), in which patient-derived DCIS epithelial cells are injected intraductally and allowed to progress naturally in mice. Similar to human DCIS, the cancer cells formed in situ lesions inside the mouse mammary ducts and mimicked all histologic subtypes including micropapillary, papillary, cribriform, solid, and comedo. Among 37 patient samples injected into 202 xenografts, at median duration of 9 months, 20 samples (54%) injected into 95 xenografts showed in vivo invasive progression, while 17 (46%) samples injected into 107 xenografts remained non-invasive. Among the 20 samples that showed invasive progression, nine samples injected into 54 xenografts exhibited a mixed pattern in which some xenografts showed invasive progression while others remained non-invasive. Among the clinically relevant biomarkers, only elevated progesterone receptor expression in patient DCIS and the extent of in vivo growth in xenografts predicted an invasive outcome. The Tempus XT assay was used on 16 patient DCIS formalin-fixed, paraffin-embedded sections including eight DCISs that showed invasive progression, five DCISs that remained non-invasive, and three DCISs that showed a mixed pattern in the xenografts. Analysis of the frequency of cancer-related pathogenic mutations among the groups showed no significant differences (KW: p > 0.05). There were also no differences in the frequency of high, moderate, or low severity mutations (KW; p > 0.05). These results suggest that genetic changes in the DCIS are not the primary driver for the development of invasive disease. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The clinical impact of MRI on surgical planning for patients with in-breast tumor recurrence.

OBJECTIVE: The objective of this study was to evaluate the clinical utility of breast MRI for patients with known in-breast tumor recurrence (IBTR). The aim was to determine if the addition of breast MRI altered surgical approach or multidisciplinary management. Previous studies have focused on using breast MRI for surgical planning for index breast cancers (BC) or detecting IBTR. However, the clinical impact of obtaining MRI in the setting of known IBTR has not been evaluated. METHODS: A single-institution retrospective chart review was performed to compare surgical approach and multidisciplinary management for patients diagnosed with isolated IBTR who did and did not undergo breast MRI following IBTR diagnosis. RESULTS: IBTR was identified in 69 patients, 46% of whom underwent MRI. There was no difference in the operative approach (p = 0.14) for IBTR patients who did and did not undergo breast MRI Additionally, there was no difference in multidisciplinary care, treatment order, metastatic disease identification, or mortality between cohorts. A relatively small subgroup of patients (n = 3) required change in surgical plan based on MRI results. Patients proceeding with surgery first who also underwent breast MRI experienced a significantly longer time to surgical intervention (p = 0.03). CONCLUSION: Breast MRI following IBTR diagnosis infrequently impacted clinical management, including surgical approach and multidisciplinary care. MRI for local disease assessment at the time of IBTR should be used selectively based on clinical concern.

Intraoperative sentinel lymph node evaluation in patients with node-positive breast cancer status post neoadjuvant systemic therapy - An institutional experience.

Recent studies have shown the feasibility and utility of sentinel lymph node (SLN) biopsy in patients with biopsy proven node-positive breast cancer after neoadjuvant chemotherapy. We reviewed our experience in intraoperative SLN evaluation in such cases and its effect on axillary management. A retrospective analysis of breast cancer patients (2015-2018) with a biopsy-proven positive axillary lymph node, who received neoadjuvant systemic therapy and underwent intraoperative SLN assessment was performed. Intraoperative SLN assessment results were compared with final pathology. Its accuracy and effect on axillary management is summarized. We identified 106 patients with positive axillary lymph node and neoadjuvant systemic therapy between the ages of 28 and 75 years who had SLN biopsy and lumpectomy (33) or mastectomy (73). Three or more SLNs were identified in 91 cases (86 %). The previously biopsied lymph node was identified as one of the sentinel lymph nodes in 93 cases (88 %). There is a high concordance rate between frozen section diagnosis and final diagnosis on sentinel lymph nodes. No false positive case and seven false negative frozen section diagnosis cases (diagnosed as negative on frozen section and positive on permanent sections) were identified. False-negative frozen section diagnosis correlated with low-volume nodal disease and obscuring tumor bed changes. Almost half of the positive lymph nodes were converted to negative after neoadjuvant chemotherapy. SLN biopsy with intraoperative frozen section evaluation after neoadjuvant systemic therapy in node-positive patients is an effective way to minimize axillary surgery.

Rethinking residency recruitment, application, and interview processes to benefit applicants and programs long-term.

Pharmacy residency recruitment and interviews have been significantly impacted by the COVID-19 pandemic. Many traditional recruitment events and interviews were transitioned from in-person to virtual, and new approaches to recruitment, such as virtual open houses, were developed. There are limited data on how these changes impacted pharmacy residency applicants and programs, and the future of virtual events is currently unknown. We highlight recommendations for virtual recruitment and interviews and provide suggestions for residency programs and national organizations to improve virtual processes in the future.

A Continuing Education Activity Durably Addressed Knowledge Gaps Related to Penicillin Allergies Among Pharmacists and Pharmacy Technicians.

Background: Penicillin allergy is one of the most frequent self-reported allergies; however, only about 10% of reported allergies are accurate. Objectives: Through the creation of a continuing pharmacy education (CPE) activity, we sought to assess knowledge gaps and comfort levels in the management of penicillin allergies. Methods: A 1-hour enduring-content CPE activity was offered as an interactive course from September 20, 2019, to September 20, 2020. Participants completed 3 surveys (pre-survey, post-survey, and follow-up survey). Participants were pharmacists and pharmacy technicians who completed, at a minimum, the activity and both pre- and post-surveys. The primary outcome was the percentage of participants scoring >80% on knowledge-based questions on the post-survey compared with the pre-survey. Secondary outcomes included pre-post comparisons on knowledge-based questions, participants' self-report of an allergy, and comfort levels dispensing cephalosporins in a patient with a self-reported penicillin allergy. Results: A total of 389 participants completed the CPE activity, with 176 included for analysis. Significantly more participants scored >80% on knowledge-based questions on the post-survey compared with the pre-survey (71.6% vs 22.7%, P < .001). There was no significant difference between the percentage of participants scoring >80% on the post-survey and the follow-up survey (71.6% vs 65%, P = .119). The majority of participants (74%) felt comfortable dispensing a cephalosporin in a patient with a penicillin allergy on the pre-survey, with similar percentages on the post- and follow-up surveys (77% and 90%, respectively). Conclusion: A targeted continuing education program improved overall knowledge, which was sustained for up to 2 months.

Is bioimpedance spectroscopy a useful tool for objectively assessing lymphovenous bypass surgical outcomes in breast cancer-related lymphedema?

PURPOSE: We sought to determine if bioimpedance spectroscopy (BIS) measurements can accurately assess changes in breast cancer-related lymphedema (BCRL) in patients undergoing lymphovenous bypass (LVB). METHODS: Patients undergoing LVB for BCRL refractory to conservative treatment from 1/2015 to 12/2018 were identified from an IRB-approved prospectively maintained database at a single institution. All breast cancer patients were assessed with baseline BIS measurements prior to any oncologic surgery and serial BIS during follow-up office visits including before and after LVB. Clinicopathologic information, LVB operative details, and pre- and post-LVB operative BIS measurements were collected. Analysis focused on clinically significant BIS change, defined as two standard deviations (SD), and comparing LVB anastomosis to BIS changes. RESULTS: During the study timeframe, nine patients underwent LVB for treatment of BCRL. The majority (78%) received radiation, taxane chemotherapy, and underwent axillary dissection. An average of 5.6 LVB anastomoses were performed per patient. The average change in BIS following LVB was a 3SD reduction, indicating a clinically significant change. This improvement was stable over time, with persistent 2SD reduction at 22 months postoperatively. The number of LVB anastomoses performed did not significantly correlate with the degree of BIS change. CONCLUSIONS: This is the first study to utilize BIS measurements to assess response to LVB surgical intervention for BCRL. BIS measurements demonstrated clinically significant improvement after LVB, providing objective evidence in support of this surgical treatment for BCRL. BIS changes should be reported as key objective data in future studies assessing BCRL interventions, including response to LVB.

Is axillary imaging for invasive lobular carcinoma accurate in determining clinical node staging?

PURPOSE: Preoperative evaluation of clinical N-stage (cN) is difficult in breast cancer patients with invasive lobular carcinoma (ILC). Our goal was to assess the predictive value of axillary imaging in ILC by comparing imaging cN and pathologic N-stage (pN). METHODS: A single-institution retrospective review was performed for newly diagnosed stage I-III ILC patients undergoing preoperative breast imaging from 2011 to 2016. Clinicopathologic factors; mammogram, MRI, and ultrasound findings; and surgical pathology data were reviewed. Sub-analysis for pN2-N3 patients was performed to determine imaging sensitivity for patients with a larger nodal disease burden. Statistical analysis included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each imaging modality. RESULTS: Of the total 349 patients included, 70.5% were cN0, and 62% were pN0 (p = 0.03). For all patients, mammogram sensitivity was 7%, specificity 97%, PPV 50%, NPV 72%; ultrasound sensitivity was 26%, specificity 86%, PPV 52%, NPV 67%; MRI sensitivity was 7%, specificity 98%, PPV 80%, NPV 51%. For pN2/N3 patients, 38% were identified as cN0. Mammogram sensitivity was 10%; ultrasound 42%; MRI 65%. Pathology evaluation of N2/N3 patients indicated LN were replaced with ILC but maintained normal architecture. The average largest pathologic tumor deposit (1.5 ± 0.8 cm) correlated with average largest imaging LN size (1.4 ± 0.6 cm) (p = 0.58). CONCLUSION: A statistically significant difference between clinical and pathologic N-stage exists for ILC patients. MRI was most sensitive for identification of pN2-N3 patients and should be considered part of routine axillary imaging evaluation for ILC patients.

Multidisciplinary Review of Intraductal Papilloma of the Breast can Identify Patients who may Omit Surgical Excision.

BACKGROUND: The purpose of this study was to define contemporary management recommendations regarding who would benefit from surgical excision of intraductal papilloma (IDP). METHODS: A prospective database from a single institution identified patients with IDP on percutaneous biopsy from February 2015 to September 2020. Categorical patient demographic, biopsy, and pathologic variables were analyzed using Fisher's exact test and continuous demographic and imaging variables using the Mann-Whitney U test. RESULTS: IDP was present in 416 biopsies, at a median age of 56 years. The median size was 0.9 cm, and the majority had greater than 50% of the target excised by biopsy. Surgical excision was performed for 124 of 416 biopsies (29.8%). Upgrade to malignancy was identified in 14 (11.3%): 8 to ductal carcinoma in situ (DCIS) and 6 to invasive cancer. Upgrade was significantly associated with concurrent ipsilateral breast cancer (p = 0.027), larger imaging size (p = 0.045), <50% excised with biopsy (p = 0.02), and atypia involving IDP (p = 0.045). Age, clinical presentation, and concurrent contralateral cancer were not significantly associated with upgrade. Lowest upgrade risk (0%) was in pure IDP ≤1 cm with >50% removed by biopsy. Of 401 biopsies that either did not upgrade or undergo excision, 7 (1.7%) developed subsequent breast cancer over a median follow-up of 23.5 months (interquartile range [IQR] 11,41), none at IDP site. CONCLUSIONS: After multidisciplinary review, the management of IDP can be stratified into low- and high-risk for upgrade groups using key criteria. Low-risk group may omit surgical excision, because those patients have 0% risk of upgrade over the limited short-term follow-up.

Does the Addition of Breast MRI Add Value to the Diagnostic Workup of Invasive Lobular Carcinoma?

BACKGROUND: Invasive lobular carcinoma (ILC) has unique histologic growth pattern. Few studies have focused on the value of breast magnetic resonance imaging (MRI) specifically for ILC. We hypothesized that MRI adds value to the diagnostic workup in ILC by better defining the extent of disease and identifying additional foci of malignancy, which can change the surgical plan. MATERIALS AND METHODS: This was a single-institution retrospective review of women diagnosed with ILC from 1/2012 to 7/2019 who underwent preoperative MRI. Patient, tumor characteristics, and initial surgical plan were reviewed. MRI had added value if ILC size correlated best to final pathologic size or if additional malignancy was identified. MRI was considered harmful if additional biopsies were benign or if the size was overestimated. RESULTS: ILC was identified in 166 breasts in 165 women. Original surgical plan was for lumpectomy in 86 (52%), mastectomy in 49 (30%), and undecided in 31 (18%). MRI changed the plan in 25 (19%) with 24 (96%) changing from lumpectomy to mastectomy. Additional biopsy was performed in 28% after MRI, the majority (n = 41, 72%) were benign or high risk and 16 (28%) identified additional malignancy. MRI was not a better size estimate than mammogram/ultrasound. Re-excision rate after lumpectomy was 6.8% (5/73). MRI added value in 48 (28.9%) and was harmful in 48 (28.9%). CONCLUSIONS: Using breast MRI in the diagnostic workup of ILC has both positive and negative implications on surgical treatment planning. A shared decision-making conversation is warranted before proceeding with MRI to maximize value and minimize harms associated with this diagnostic tool.

Secondary angiosarcoma following catheter-based brachytherapy.

Secondary angiosarcoma of the breast following catheter-based brachytherapy after lumpectomy is rare. We describe a case of a patient with breast cancer treated with partial mastectomy and sentinel node biopsy followed by accelerated partial breast irradiation (APBI), who developed skin changes 6 years after completion of therapy. Punch biopsy confirmed the diagnosis of secondary angiosarcoma. This case is even more unique in that the location of the skin changes was remote to the lumpectomy site. There is a critical need to recognize secondary angiosarcoma presentation after APBI and determine the rate of occurrence compared with traditional external beam irradiation.

The utility of intraoperative retroareolar margin frozen section assessment and the management of atypical epithelial proliferative lesions at the retroareolar margin in nipple-sparing mastectomies.

OBJECTIVES: Nipple-sparing mastectomy (NSM) has become more frequently utilized due to superior psychological and cosmetic outcomes. The aim of this study was to evaluate the accuracy and utility of intraoperative frozen section evaluation of the retroareolar margin (RAM) in NSM. The management of atypical epithelial proliferative lesions at the RAM was also reviewed and discussed. METHODS: A single institution, retrospective analysis was performed on all therapeutic NSM patients with intraoperative evaluation of the RAM from 2014 to 2018. Patient demographics, tumor characteristics, pathologic assessment of the RAM, surgical management, and clinical follow-up were reviewed. RESULTS: Seventy-four nipple-sparing mastectomies with intraoperative evaluation of RAMs were identified. Concordance was 95% between frozen and permanent section diagnoses with 4 cases representing false negatives and no false positives. There were no instances of nipple-areolar complex (NAC) recurrence in all cases with preserved NACs (mean follow up: 750 days). In the 9 cases where NACs were excised based on intraoperative RAM evaluation, the findings in the excised NACs were negative in 6 and ductal carcinoma in situ in 3 cases. Postoperative measurement of the tumor to nipple distance was the only statistically significant variable associated with a positive RAM by multivariable logistic regression (OR 0.475; 95% CI 0.238-0.946). CONCLUSIONS: Intraoperative RAM evaluation demonstrated high concordance with permanent histology. Negative RAM, including atypical epithelial proliferative lesions, led to NAC preservation without recurrence. Positive RAM alone did not predict NAC involvement, although pagetoid spread of ductal carcinoma in situ along nipple ducts may predict NAC positivity.

Effect of Obesity on Clinical Outcomes of Patients Treated With Cefepime.

Background: As the prevalence of obesity climbs, dosing of antimicrobials, particularly cephalosporins, is becoming a greater challenge for clinicians. Data are lacking for appropriate dosing of cefepime, an anti-pseudomonal cephalosporin that is widely used as an empiric anti-pseudomonal agent. Objective: The purpose of this study was to determine the rate of clinical treatment failure in obese patients compared with nonobese patients receiving cefepime as definitive monotherapy. Methods: Adult inpatients treated with cefepime monotherapy for ≥72 hours were included. Patients were excluded if they (1) were not able to achieve culture clearance within 72 hours and (2) had polymicrobial infections requiring more than one antibiotic for definitive therapy. Results: Fifty-eight obese patients and 56 nonobese patients were included. Pseudomonas aeruginosa, Escherichia coli, and Enterobacter spp were the most prevalent organisms isolated. Most organisms had a minimum inhibitory concentration of ≤1 µg/mL to cefepime with no differences in minimum inhibitory concentration distributions between groups. Definitively, 60% of patients received cefepime 1 g, while almost 40% received cefepime 2 g. Clinical failure occurred in 52% of patients (67% obese vs 36% nonobese; P = .001), with study group (odds ratio = 1.057, 95% confidence interval = 1.008-1.109) and respiratory source (odds ratio = 3.251, 95% confidence interval = 1.378-7.667) being independent predictors of failure. There were no differences in hospital length of stay, all-cause mortality, or 30-day readmissions. Conclusions: Obese patients treated with cefepime are more likely to experience treatment failure than nonobese patients. Larger trials examining the reasons for clinical failure in obese patients treated with cefepime are needed to confirm the findings from this preliminary work.

Developing and Monitoring a Standard-of-Care Chimeric Antigen Receptor (CAR) T Cell Clinical Quality and Regulatory Program.

As the world of cellular therapy expands to include immune effector cell (IEC) products such as commercial chimeric antigen receptor (CAR) T cells, quality management (QM) professionals are faced with creating either new IEC stand-alone programs or expand existing hematopoietic cell transplantation (HCT) programs to promote patient safety and be aligned with quality, regulatory, and accreditation requirements. The team professionals at City of Hope (COH) recently expanded the quality HCT program to include IEC products and, in doing so, implemented new regulatory infrastructure while maintaining high quality patient care. At COH, we developed the quality structure of our cellular therapy program through collaborations between quality, regulatory, and CAR T patient care committees, which included physicians and nurse coordinators. To ensure the quality of our program, we monitor data collection and reporting, perform quarterly proactive audits of, for example, outcome analysis, and measure selected end-points for benchmarking purposes. QM professionals play a critical role in the monitoring and evaluation processes and provide guidance on how to implement accreditation requirements and what impact the requirements may have on care management. Here we describe the process by which COH expanded our HCT QM program to include IEC therapy. We share examples of how we developed our overall program structure and other key items such as how we addressed patient care management and accreditation to apprise other programs that wish to create and/or expand existing programs.

Ipsilateral and Concurrent Breast Cancer and Atypical Ductal Hyperplasia: Does Atypia Also Need Surgical Excision?

BACKGROUND: Standard-of-care management of atypical ductal hyperplasia (ADH) is surgical excision. Multiple studies have identified features of ADH in patients at low risk for upgrade who may benefit from omission of surgical excision. Patients with an ipsilateral breast cancer have been excluded from studies investigating observation for the management of ADH. METHODS: This was a retrospective review of women with both a breast cancer and an ipsilateral separate site of ADH diagnosed on percutaneous biopsy, who underwent excision of both sites from 2008 to 2018. Radiographic and pathologic features of ADH and cancer were analyzed, including imaging size, biopsy modality, distance between sites, cancer subtype, grade, prognostic markers, ADH foci, and presence of necrosis or micropapillary features. Final pathology at the ADH site was used to determine upgrade. Multivariable logistic regression was performed to identify variables significantly associated with ADH upgrade to malignancy. RESULTS: Among 62 women meeting the inclusion criteria, 11 (17.7%) upgraded to malignancy [9 ductal carcinoma in situ (DCIS), 2 invasive cancer] at the site of ADH. Upgrade was significantly higher with ipsilateral DCIS (p = 0.03), ultrasound biopsy at the ADH site (p = 0.01), and ADH with necrosis (p = 0.04). The group at lowest risk for upgrade had stereotactic biopsy and ADH without necrosis (0% upgrade). CONCLUSION: The presence of breast cancer does not significantly increase the likelihood for upgrade at a separate site of ipsilateral concurrent ADH above contemporary reported upgrade rates of ADH alone (10-30%). When considering breast conservation for breast cancer, omitting excision of the site of ADH can be considered when low-risk features are present.

Primary tumor resection in de novo stage IV breast cancer patients.

Breast and axillary surgery in Stage IV disease is outside current national guidelines but has been a topic of ongoing debate. A single institution retrospective study identified women with de novo stage IV BC from 2011-2016 to evaluate the rate and goals of primary site surgery. Only 10.2% (n = 27/265patients) had primary site surgery. The goal of surgery was most often treatment intent (n = 23, 85.1%) not palliation (n = 4, 14.8%). There was no 30-day mortality and low (n = 1, 3.7%) 30-day morbidity. Multi-disciplinary patient care pathways based on modern evidence may help identify patients potentially suitable for primary site surgery.

Trends in and Predictors of Carbapenem Consumption across North American Hospitals: Results from a Multicenter Survey by the MAD-ID Research Network.

We sought to define trends in and predictors of carbapenem consumption across community, teaching, and university-affiliated hospitals in the United States and Canada. We conducted a retrospective multicenter survey of carbapenem and broad-spectrum noncarbapenem beta-lactam consumption between January 2011 and December 2013. Consumption was tabulated as defined daily doses (DDD) or as days of therapy (DOT) per 1,000 patient days (PD). Multivariate mixed-effects models were explored, and final model goodness of fit was assessed by regressions of observed versus predicted values and residual distributions. A total of 20 acute-care hospitals responded. The centers treated adult patients (n = 19/20) and pediatric/neonatal patients (n = 17/20). The majority of the centers were nonprofit (n = 17/20) and not affiliated with medical/teaching institutions (n = 11/20). The median (interquartile range [IQR]) carbapenem consumption rates were 38.8 (17.4 to 95.7) DDD/1,000 PD and 29.7 (19.2 to 40.1) DOT/1,000 PD overall. Carbapenem consumption was well described by a multivariate linear mixed-effects model (fixed effects, R2 = 0.792; fixed plus random effects, R2 = 0.974). Carbapenem consumption increased by 1.91-fold/quarter from 48.6 DDD/1,000 PD (P = 0.004) and by 0.056-fold/quarter from 45.7 DOT/1,000 PD (P = 0.93) over the study period. Noncarbapenem consumption was independently related to increasing carbapenem consumption (beta = 0.31 for increasing noncarbapenem beta-lactam consumption; P < 0.001). Regular antibiogram publication and promotion of conversion from intravenous (i.v.) to oral (p.o.) administration independently affected carbapenem consumption rates. In the final model, 58.5% of the observed variance in consumption was attributable to between-hospital differences. Rates of carbapenem consumption across 20 North American hospitals differed greatly, and the observed differences were correlated with hospital-specific demographics. Additional studies focusing on the drivers of hospital-specific carbapenem consumption are needed to determine whether these rates are justifiable.

Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy.

A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)-engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2). Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes - infusions into the resected tumor cavity followed by infusions into the ventricular system. Intracranial infusions of IL13Rα2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher. After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. This clinical response continued for 7.5 months after the initiation of CAR T-cell therapy. (Funded by Gateway for Cancer Research and others; ClinicalTrials.gov number, NCT02208362 .).

A Randomized Trial Evaluating Bioimpedance Spectroscopy Versus Tape Measurement for the Prevention of Lymphedema Following Treatment for Breast Cancer: Interim Analysis.

BACKGROUND: Breast cancer-related lymphedema (BCRL) represents a major source of morbidity among breast cancer survivors. Increasing data support early detection of subclinical BCRL followed by early intervention. A randomized controlled trial is being conducted comparing lymphedema progression rates using volume measurements calculated from the circumference using a tape measure (TM) or bioimpedance spectroscopy (BIS). METHODS: Patients were enrolled and randomized to either TM or BIS surveillance. Patients requiring early intervention were prescribed a compression sleeve and gauntlet for 4 weeks and then re-evaluated. The primary endpoint of the trial was the rate of progression to clinical lymphedema requiring complex decongestive physiotherapy (CDP), with progression defined as a TM volume change in the at-risk arm ≥ 10% above the presurgical baseline. This prespecified interim analysis was performed when at least 500 trial participants had ≥ 12 months of follow-up. RESULTS: A total of 508 patients were included in this analysis, with 109 (21.9%) patients triggering prethreshold interventions. Compared with TM, BIS had a lower rate of trigger (15.8% vs. 28.5%, p < 0.001) and longer times to trigger (9.5 vs. 2.8 months, p = 0.002). Twelve triggering patients progressed to CDP (10 in the TM group [14.7%] and 2 in the BIS group [4.9%]), representing a 67% relative reduction and a 9.8% absolute reduction (p = 0.130). CONCLUSIONS: Interim results demonstrated that post-treatment surveillance with BIS reduced the absolute rates of progression of BCRL requiring CDP by approximately 10%, a clinically meaningful improvement. These results support the concept of post-treatment surveillance with BIS to detect subclinical BCRL and initiate early intervention.