Citations

Abstract Background: Breast cancer (BC) treatment, including surgery, can impact not only short-term health outcomes but may also affect longer term health-related and psychosocial quality of life (QOL). We sought to describe the impact of BC surgery on QOL among breast cancer survivors followed in a large randomized trial. Methods: The ECOG-ACRIN protocol E5103 was a phase III trial that randomized BC patients (pts) who had undergone definitive BC surgery to receive adjuvant doxorubicin, cyclophosphamide, and paclitaxel with either bevacizumab (bev) or placebo. Telephone based surveys were administered to all pts enrolled between 01/Jan/10 and 08/Jun/10 as part of a Decision-Making/QOL component until 18 mos post enrollment. Functional/psychosocial QOL domains were assessed by the EQ-5D-3L and the FACT B+G. Fisher's exact test compared categorical and Wilcoxon rank sum test compared continuous variables between subgroups. Multivariable regression was used to evaluate factors in addition to primary surgery at enrollment (age, race, ER/PgR status, tumor size, nodal status) associated with overall FACT score at 18 mos. Results: Patient reported outcomes at 18 mos were available from 89.6% (465/519) pts. At enrollment, 57% (266/465) had a mastectomy; 43% (199/465) breast conserving surgery (BCS). Median age at enrollment was 52 (range: 25-76) years. There were no differences in QOL between bev vs placebo treatment arms (EQ-5D-3L Index Score p=0.65; FACT B+G Score p=0.23) at 18 mos so groups were combined. Using EQ-5D-3L, over half of the pts (58%) reported at least some pain/discomfort; 38% symptoms of anxiety/depression. A higher proportion of mastectomy pts reported problems with usual activities compared to BCS pts (Table). Compared to BCS pts, mastectomy pts had lower average EQ5D-3L scores 0.80 vs. 0.84, p=0.04 and FACT B+G scores 109 vs. 114, p=0.01, indicating worse QOL. In univariate analyses, non-white race (p=0.03), ER/PgR+ status (p=0.04) and mastectomy as primary surgery (p=0.01) were significantly associated with worse QOL (lower FACT B+G scores). In multivariable analyses, non-white race (p=0.02) and ER/PgR+ status (p=0.05) remained associated with worse QOL; mastectomy was borderline significant (p=0.06). Conclusions: Among women participating in a contemporary adjuvant BC chemotherapy trial, a substantial proportion of survivors experience symptoms that may be amenable to intervention, including referral to physical rehabilitation, especially among pts undergoing more extensive surgery. Attention to psychosocial health is also essential both during and after completion of active treatment to optimize QOL outcomes. N(%) reporting problems* 5 DimensionsBCSMastectomyOverallp**Mobility44(23)59(23)103(23)1.00Self-care11(6)23(9)34(7)0.21Usual activities49(25)90(34)139(30)0.04Pain/discomfort104(53)161(61)265(58)0.08Anxiety/depression70(36)105(40)175(38)0.44*3L: 3 possible answers: 1) no problems 2) some/moderate problems 3) problems; responses then collapsed into no problems vs. any problems' (=some/moderate problems and problems). ** Fisher's exact test p-value. Citation Format: Rosenberg SM, O'Neill A, Sepucha K, Miller KD, Dang CT, Northfelt DW, Sledge GW, Schneider BP, Partridge AH. The impact of breast cancer surgery on quality of life: Long term results from E5103 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-05.

OBJECTIVE Since the enactment of the Affordable Care Act in 2010, providers and hospitals have increasingly prioritized patient-centered outcomes such as patient satisfaction in an effort to adapt the “value”-based healthcare model. In the current study, the authors queried a prospectively maintained multiinstitutional spine registry to construct a predictive model for long-term patient satisfaction among patients undergoing surgery for Meyerding grade I lumbar spondylolisthesis. METHODS The authors queried the Quality Outcomes Database for patients undergoing surgery for grade I lumbar spondylolisthesis between July 1, 2014, and June 30, 2016. The primary outcome of interest for the current study was patient satisfaction as measured by the North American Spine Surgery patient satisfaction index, which is measured on a scale of 1–4, with 1 indicating most satisfied and 4 indicating least satisfied. In order to identify predictors of higher satisfaction, the authors fitted a multivariable proportional odds logistic regression model for ≥ 2 years of patient satisfaction after adjusting for an array of clinical and patient-specific factors. The absolute importance of each covariate in the model was computed using an importance metric defined as Wald chi-square penalized by the predictor degrees of freedom. RESULTS A total of 502 patients, out of a cohort of 608 patients (82.5%) with grade I lumbar spondylolisthesis, undergoing either 1- or 2-level decompression (22.5%, n = 113) or 1-level decompression and fusion (77.5%, n = 389), met the inclusion criteria; of these, 82.1% (n = 412) were satisfied after 2 years. On univariate analysis, satisfied patients were more likely to be employed and working (41.7%, n = 172, vs 24.4%, n = 22; overall p = 0.001), more likely to present with predominant leg pain (23.1%, n = 95, vs 11.1%, n = 10; overall p = 0.02) but more likely to present with lower Numeric Rating Scale score for leg pain (median and IQR score: 7 [5–9] vs 8 [6–9]; p = 0.05). Multivariable proportional odds logistic regression revealed that older age (OR 1.57, 95% CI 1.09–2.76; p = 0.009), preoperative active employment (OR 2.06, 95% CI 1.27–3.67; p = 0.015), and fusion surgery (OR 2.3, 95% CI 1.30–4.06; p = 0.002) were the most important predictors of achieving satisfaction with surgical outcome. CONCLUSIONS Current findings from a large multiinstitutional study indicate that most patients undergoing surgery for grade I lumbar spondylolisthesis achieved long-term satisfaction. Moreover, the authors found that older age, preoperative active employment, and fusion surgery are associated with higher odds of achieving satisfaction.

Background: Long QT syndrome is a potentially lethal yet highly treatable cardiac channelopathy. Although β-blocker therapy is standard for most patients, concomitant therapy with sodium channel blockers, like mexiletine, is often utilized for patients with sodium channel–mediated type 3 long QT syndrome (LQT3). The potential role of sodium channel blockers in patients with potassium channel–mediated long QT syndrome (ie, LQT1 and LQT2) has not been investigated in detail. Methods: We performed a retrospective chart review on 12 patients (5 females; median age at diagnosis 14.1 years (interquartile range [IQR], 7.7–23; range, 0–59, median heart rate–corrected QT interval [QTc] at diagnosis 557 ms (IQR, 529–605) with genetically established LQT2 (10) or a combination of LQT1/LQT2 (1) or LQT2/LQT3 (1), who received mexiletine. Data were collected on symptomatic status, treatments, and breakthrough cardiac events after diagnosis and initiation of treatment. Additionally, 12-lead ECGs were collected at diagnosis, before initiation of mexiletine and following mexiletine to evaluate the drug’s effect on QTc. Results: Before diagnosis, 6 patients were symptomatic and, before initiation of mexiletine, 4 patients experienced ≥1 breakthrough cardiac event on β-blocker. Median age at first mexiletine dose was 24.3 years (IQR, 14–32.4). After mexiletine, the median QTc decreased by 65±45 ms from 547 ms (IQR, 488–558) premexiletine to 470 ms (IQR, 409–529) postmexiletine ( P =0.0005) for all patients. In 8 patients (67%), the QTc decreased by ≥ 40 ms with a mean decrease in QTc of 91 ms ( P < 0.008). For the 11 patients maintained on mexiletine therapy, there have been no breakthrough cardiac events during follow-up. Conclusions: Although commonly prescribed in patients with LQT3, mexiletine also shortens the QTc significantly in two-thirds of a small subset of patients with potassium channel–mediated LQT2. In patients with LQT2, pharmacological targeting of the physiological late sodium current may provide added therapeutic efficacy to β-blocker therapy.

AbstractPurposeIt is unclear if a 3D transducer with the special design of mechanical swing or 2D array could provide acceptable 2D grayscale image quality for the general diagnosis purpose. The aim of this study is to compare the 2D image quality of a 3D intracavitary transducer with a conventional 2D intracavitary transducer using clinically relevant phantom experiments.MethodsAll measurements were performed on a GE Logiq E9 scanner with both a 2D (IC5‐9‐D) and a 3D (RIC5‐9‐D) transducer used in 2D mode. Selection of phantom targets and acquisition parameters were determined from analysis of 33 clinical pelvic exams. Depth of penetration (DOP), contrast response, contrast of anechoic cylinders (diameter: 6.7 mm) at 1.5 and 4.5 cm depths in transverse planes, and in‐plane resolution represented by full‐width half‐maximum of pin targets at multiple depths were measured with transmit frequencies of 7 and 8 MHz. Spherical signal‐noise‐ratio (SNR) (diameter: 4 and 2 mm) at multiple depths were measured at 8 MHz.ResultsRIC5‐9‐D demonstrated <8% decrease in DOP for both transmit frequencies (7 MHz: 69.7 ± 8.2 mm; 8 MHz: 64.3 ± 7.8 mm) compared with those from IC5‐9‐D (7 MHz: 73.9 ± 4.4 mm; 8 MHz: 69.4 ± 7.8 mm). A decreased anechoic contrast was observed with a 4.5 cm depth for RIC5‐9‐D (7 MHz: 23.2 ± 1.8 dB, P > 0.05; 8 MHz: 17.7 ± 0.9 dB, P < 0.01) compared with IC5‐9‐D (7 MHz: 25.9 ± 1.2 dB; 8 MHz: 21.5 ± 0.8 dB). The contrast response and spatial resolution performance were comparable between the two transducers. RIC5‐9‐D showed comparable SNR of anechoic spheres compared to IC5‐9‐D.Conclusions2D images from a 3D probe exhibited comparable overall image quality for routine clinical pelvic imaging.

AbstractMicroglial activation has been recognized as a major contributor to inflammation of the epileptic brain. Seizures are commonly accompanied by remarkable microgliosis and loss of neurons. In this study, we utilize the CX3CR1GFP/+ CCR2RFP/+ genetic mouse model, in which CX3CR1+ resident microglia and CCR2+ monocytes are labeled with GFP and RFP, respectively. Using a combination of time‐lapse two‐photon imaging and whole‐cell patch clamp recording, we determined the distinct morphological, dynamic, and electrophysiological characteristics of infiltrated monocytes and resident microglia, and the evolution of their behavior at different time points following kainic acid‐induced seizures. Seizure activated microglia presented enlarged somas with less ramified processes, whereas, infiltrated monocytes were smaller, highly motile cells that lacked processes. Moreover, resident microglia, but not infiltrated monocytes, proliferate locally in the hippocampus after seizure. Microglial proliferation was dependent on the colony‐stimulating factor 1 receptor (CSF‐1R) pathway. Pharmacological inhibition of CSF‐1R reduced seizure‐induced microglial proliferation, which correlated with attenuation of neuronal death without altering acute seizure behaviors. Taken together, we demonstrated that proliferation of activated resident microglia contributes to neuronal death in the hippocampus via CSF‐1R after status epilepticus, providing potential therapeutic targets for neuroprotection in epilepsy.

Background: Cementation of a constrained liner is a viable option for treating instability after total hip arthroplasty (THA) when the acetabular component is well fixed and well aligned. However, concerns regarding long-term mechanical failure and recurrent instability remain. The aim of this study was to evaluate the long-term survivorship, complications, and clinical and radiographic outcomes of constrained polyethylene liners cemented into well-fixed acetabular components at the time of revision THA. Methods: We identified 125 cases in which a constrained liner of 1 design was cemented into a retained, osseointegrated acetabular component during revision THA between 1998 and 2006. The mean patient age at revision was 70 years. Mean follow-up was 7 years. Survivorship data, risk of instability, and clinical and radiographic outcomes were analyzed. Results: Survivorship free from revision for instability was 86% at 5 years and 81% at 10 years. Survivorship free from aseptic acetabular component revision was 78% at 5 years and 65% at 10 years, with the most common failure mechanism being dissociation of the constrained liner from the acetabular component. Survivorship free from revision for any reason was 76% at 5 years and 60% at 10 years. The most common complications were instability and periprosthetic joint infection, with cumulative incidences at 7 years of 18% and 11%, respectively. Harris hip scores did not significantly improve. Cup position did not affect implant survivorship or risk of dislocation. Conclusions: Cementing a constrained liner into a retained acetabular shell at the time of revision THA has durable long-term results, with 8 in 10 patients free from instability at 10 years. Aseptic acetabular survivorship was worse (65%) at 10 years, primarily due to dissociation of the constrained liner from the acetabular component. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.