Cytogenetic and survival analysis in 315 multiple myeloma patients; five with orbital and eight with extramedullary disease.

PURPOSE: To describe cytogenetic abnormalities in five patients with orbital involvement of multiple myeloma (MM) and to determine if high-risk cytogenetic abnormalities were more prevalent in patients with extramedullary disease (EMD). The final goal was to determine predictors of poor survival in the entire cohort. METHODS: Retrospective cohort study of 315 patients diagnosed with multiple myeloma over a 9-year period at a single institution. RESULTS: Males comprised 61% of the 315 patients and the majority (54.3%) were stage II at diagnosis of MM. Follow-up ranged 6 months to 18 years, mean 5.3 ± 3.7 years. Eight patients (2.5%), two of which had orbital involvement, developed EMD and an additional three patients had orbital involvement from adjacent bone disease. No genetic abnormality reached statistical significance between non-EMD and EMD groups. At the time of analysis 127 (41%) non-EMD patients and 6 (75%) EMD patients have died. The median survival time for the EMD group was 2 years, whereas for the non-EMD group it was 9 years (P-value of log rank test = .00015). Stage at time of MM diagnosis and age were associated with worse prognosis. Median survival for patients over 65 years of age was 7 years, compared to 12 years for patients 65 or younger (P-value for the log-ranked test <.001). CONCLUSIONS: Cytogenetic abnormalities are described in five patients with orbital involvement of MM. No genetic abnormality reached statistical significance between non-EMD and EMD groups. EMD status, stage of MM at diagnosis and age are associated with poorer overall survival.Abbreviation: MM: Multiple Myeloma; EMD: Extramedullary disease; FISH: fluorescence in situ hybridization; B2M: beta-2 microglobulin; LDH: lactate dehydrogenase; OS: overall survival.

Visual recovery after unilateral optic nerve sheath fenestration for pseudotumor cerebri syndrome.

PURPOSE: To evaluate the effect of optic nerve sheath fenestration (ONSF) on the rate of visual function improvement in patients with pseudotumor cerebri syndrome (PTCS). METHODS: Retrospective chart review of patients with PTCS who underwent ONSF between 1998 and 2017. Visual function was evaluated by evaluating visual field (VF), mean deviation (MD), retinal nerve fiber layer (RNFL) thickness, papilledema grade, and visual acuity (VA) prior to and after ONSF. RESULTS: Seventeen female patients aged 17 to 36 years underwent unilateral ONSF. Follow-up averaged 40.1 months. VF MD improved steadily in both eyes up to 12 months. Average RNFL thickness improved in the operated eye from 347 ± 166 mm to 92 ± 27 mm (p < .001) and the non-operated eyes from 306 ± 165 mm to 109 ± 46 mm (p < .001). The grade of papilledema improved in the operated eye from 3.3 ± 1.3 to 0.3 ± 0.7 and the non-operated eye from 3.0 ± 1.6 to 0.18 ± 0.4. There was an exponential rate of improvement in papilledema and RNFL thickness, with the greatest improvement occurring within the first 30 days. Average visual acuity remained intact in both eyes before and after surgery. CONCLUSIONS: ONSF in appropriately selected patients leads to rapid improvement in papilledema and a steady recovery in VF.

Long-term Outcome After Acute Peripheral Facial Palsy.

PURPOSE: To analyze long-term outcomes in a large cohort of patients with acute peripheral facial palsy (APFP). METHODS: Hospital-based, cross-sectional study. Data were abstracted from the electronic medical record. Time to recovery was assessed with Kaplan-Meier survival analyses. Binary logistic regression analysis was used to identify factors associated with outcome. RESULTS: Three hundred seventy-two patients with APFP seen at a tertiary hospital between February 2015 and March 2021 were analyzed. Seasonal variation of APFP peaked in the early fall (September 29) and had a peak-to-low ratio of 1.36 (R 2 = 0.329, p < 0.001). Patients who tested positive for Lyme disease (10%) had an earlier peak (July 16) compared with those who were negative (October 15). Eighty-seven percent of patients had complete recovery (averaging 64 ± 61 days). Patients, with higher House-Brackmann (H-B) grades at presentation took longer to recover, were more likely to have aberrant regeneration and had lower final rates of recovery compared with those with lower H-B grades (χ 2 = 12.03, p < 0.001). Of the patients with residual palsies, 70% had evidence of aberrant regeneration, and nearly half of those had hemifacial spasm. CONCLUSIONS: Most patients with APFP achieve complete recovery within 1 year, including those positive for Lyme. More severe palsy at presentation portends a worse outcome.

Combining Clinical and Pathologic Staging Variables Has Prognostic Value in Predicting Local-regional Recurrence Following Neoadjuvant Chemotherapy for Breast Cancer.

OBJECTIVE: The current study was undertaken to determine if the CPS+EG score could stratify patients with respect to local-regional recurrence (LRR). BACKGROUND: We previously defined and validated a novel breast cancer staging system incorporating the American Joint Committee on Cancer clinical stage (CS), final pathologic stage (PS), estrogen receptor status (E), and nuclear grade (G) (CPS+EG score). The score is associated with disease-specific survival outcomes in patients treated with neoadjuvant chemotherapy. METHODS: Patients receiving neoadjuvant chemotherapy between 1997 and 2005 were identified and clinicopathologic data were used to determine the CPS+EG score. Type of local therapy, breast-conserving therapy, mastectomy alone, or mastectomy followed by postmastectomy radiation therapy was recorded. Multivariate analysis, including CPS+EG score and local therapy, was performed to evaluate for association with LRR. RESULTS: Of 1697 patients, breast conserving therapy was performed in 656 (39%), mastectomy in 297 (17%) and mastectomy + postmastectomy radiation therapy in 744 (44%). At a median follow-up of 49 months, the crude incidence of LRR was 6.5%. Freedom from LRR at 5 years ranged from 86% to 97% by clinical stage, 86% to 97% by pathologic stage, and 71% to 99% by CPS+EG score. On multivariate analysis, CPS+EG score and surgery type were independently associated with LRR, with increased risk among patients with CPS+EG scores of 3 or greater (HR 1.94, 95% CI 1.04-3.63) or mastectomy alone (HR 2.14, 95% CI 1.26-3.63). CONCLUSIONS: The CPS+EG staging system better stratifies patients with respect to LRR after neoadjuvant chemotherapy than presenting clinical stage or final pathologic stage. For CPS+EG scores ≥3, use of postmastectomy radiation therapy decreases the likelihood of LRR after mastectomy.

Locoregional Control According to Breast Cancer Subtype and Response to Neoadjuvant Chemotherapy in Breast Cancer Patients Undergoing Breast-conserving Therapy.

BACKGROUND: Our group previously published data showing that patients could be stratified by constructed molecular subtype with respect to locoregional recurrence (LRR)-free survival after neoadjuvant chemotherapy and breast-conserving therapy (BCT). That study predated use of trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive patients. The current study was undertaken to determine the impact of subtype and response to therapy in a contemporary cohort. METHODS: Clinicopathologic data from 751 breast cancer patients who received neoadjuvant chemotherapy (with trastuzumab if HER2(+)) and BCT from 2005 to 2012 were identified. Hormone receptor (HR) and HER2 status were used to construct molecular subtypes: HR(+)/HER2(-) (n = 369), HR(+)/HER2(+) (n = 105), HR(-)/HER2(+) (n = 58), and HR(-)/HER2(-) (n = 219). Actuarial rates of LRR were determined by the Kaplan-Meier method and compared by the log-rank test. Multivariate analysis was performed to determine factors associated with LRR. RESULTS: The pathologic complete response (pCR) rates by subtype were as follows: 16.5% (HR(+)/HER2(-)), 45.7% (HR(+)/HER2(+)), 72.4% (HR(-)/HER2(+)), and 42.0% (HR(-)/HER2(-)) (P < 0.001). Median follow-up was 4.6 years. The 5-year LRR-free survival rate for all patients was 95.4%. Five-year LRR-free survival rates by subtype were 97.2 % (HR(+)/HER2(-)), 96.1% (HR(+)/HER2(+)), 94.4% (HR(-)/HER2(+)), and 93.4% (HR(-)/HER2(-)) (P = 0.44). For patients with HR(-)/HER2(+) disease, the LRR-free survival rates were 97.4 and 86.7% for those who did and those who did not experience pCR, respectively. For patients with HR(-)/HER2(-) disease, the LRR-free survival rates were 98.6% (pCR) versus 89.9% (no pCR). On multivariate analysis, the HR(-)/HER2(-) subtype, clinical stage III disease, and failure to experience a pCR were associated with LRR. CONCLUSIONS: Patients undergoing BCT after neoadjuvant chemotherapy have excellent rates of 5-year LRR-free survival that are affected by molecular subtype and by response to neoadjuvant chemotherapy.

Learning anatomy changes from patient populations to create artificial CT images for voxel-level validation of deformable image registration.

The purpose of this study was to develop an approach to generate artificial computed tomography (CT) images with known deformation by learning the anatomy changes in a patient population for voxel-level validation of deformable image registration. Using a dataset of CT images representing anatomy changes during the course of radiation therapy, we selected a reference image and registered the remaining images to it, either directly or indirectly, using deformable registration. The resulting deformation vector fields (DVFs) represented the anatomy variations in that patient population. The mean deformation, computed from the DVFs, and the most prominent variations, which were captured using principal component analysis (PCA), composed an active shape model that could generate random known deformations with realistic anatomy changes based on those learned from the patient population. This approach was applied to a set of 12 head and neck patients who received intensity-modulated radiation therapy for validation. Artificial planning CT and daily CT images were generated to simulate a patient with known anatomy changes over the course of treatment and used to validate the deformable image registration between them. These artificial CT images potentially simulated the actual patients' anatomies and also showed realistic anatomy changes between different daily CT images. They were used to successfully validate deformable image registration applied to intrapatient deformation.

A method to estimate composite doses for organs at risk in prostate cancer patients treated with EBRT in combination with HDR BT.

BACKGROUND: When evaluating late toxicity after combined external beam radiation therapy (EBRT) and high-dose rate brachytherapy (HDR BT) prostate cancer treatments, it is important that the composite dose distribution is taken into account. This can be challenging if organ-at-risk (OAR) dose data are incomplete, i.e. due to a limited ultrasound imaging field-of-view in the HDR BT procedure. This work proposes a method that provides estimates of composite OAR doses for such situations. MATERIAL AND METHODS: Original EBRT, simulated HDR BT, and composite dose-volume histograms (DVHs) for 10 pelvic OARs in 30 prostate cancer cases were used for method implementation and evaluation (EBRT: 25×2.0 Gy+BT: 2×10.0 Gy). The proposed method used information from the EBRT DVH to estimate OAR BT doses (with or without fractionation correction). Coefficients of determination (R2) were calculated for linear relationships between several EBRT DVH parameters and a BT DVH parameter of interest. The largest R2 value decided the relationship that best predicted the BT DVH parameter. The composite dose value was then calculated by adding the EBRT DVH and the estimated BT DVH parameter values and was compared to the reference composite value (in 1200 OAR/patient/parameter cases). RESULTS: The linear relationships had an average R2 of 0.68 (range 0.42-0.88). Only one ninth of the 1200 estimated composite DVH values differed more than 2 Gy from their reference values. CONCLUSION: Given a successful implementation, the proposed method only requires original or simulated BT plan data for a subset of patients to estimate composite doses for large study populations in a time-efficient manner. This can assist in evaluating radiation-induced late toxicity in multimodality treatments with limited OAR dose data.

Is there an impact of heart exposure on the incidence of radiation pneumonitis? Analysis of data from a large clinical cohort.

BACKGROUND: The goal of the present study was to determine, in a large clinical cohort, whether incidental radiation exposure to the heart during definitive radiotherapy of inoperable non-small cell lung cancer (NSCLC) detectably increased the risk of radiation pneumonitis (RP) beyond that resulting from radiation exposure to lung. MATERIAL AND METHODS: Data were analyzed from all patients who received definitive three-dimensional (3D) concurrent radiotherapy or intensity-modulated radiotherapy for the treatment of NSCLC over a 10-year period at our institution, except those who had previous lung cancer or for whom radiation treatment plans were unavailable for calculation of heart and lung dose-volume histograms (DVHs). Parameters computed from heart and lung DVHs included mean lung dose (MLD), effective lung dose computed using volume parameter n = 0.5 (Deff), mean heart dose (MHD), percentage of heart receiving > 65 Gy (V65), and minimum dose to the hottest 10% of heart (D10). Univariate and multivariate normal-tissue complication probability (NTCP) models were used to analyze incidence of Grade ≥ 2 or Grade ≥ 3 RP as a function of these and other parameters. RESULTS: The study cohort included 629 patients, with crude rates of Grade ≥ 2 RP and Grade ≥ 3 RP of N = 263 (42%) and N = 124 (20%), respectively. Univariate NTCP models based on dosimetric lung parameters (MLD and Deff) fit the data better than models based on univariate heart parameters (heart D10, heart V65 or MHD). In multivariate modeling, incorporation of heart parameters did not significantly improve the fit of RP risk models based on lung parameters alone (p > 0.38 in each case). CONCLUSIONS: In this large clinical cohort, there was no evidence that incidental heart exposure during radiotherapy of NSCLC had a detectable impact on the occurrence of moderate or severe RP.

Feasibility of a community-based structured exercise program for persons with spinal cord injury.

OBJECTIVES: (1) Examine the feasibility of a community-based exercise intervention for persons with spinal cord injury and (2) compare the cardiorespiratory fitness, skeletal muscle strength, and psychosocial well-being of participants in the intervention group versus control group. DESIGN: Community-based pilot randomized controlled trial. Setting: Accessible community-based health and wellness center. Participants: Thirty-two sedentary community-dwelling adults with any level of spinal cord injury. Interventions: Participants were randomized to a 36-session/12-week community-based exercise program (intervention; EG) or to a 36-session/12-week physical activity education group (control; CG). Outcome measures: Primary outcome measures included cardiorespiratory fitness measured by a VO2peak test, a composite score of four upper extremity musculoskeletal strength 1-repetition maximum exercises, and feasibility measured by EG participants' adherence and exercise intensity achieved during the program. EG participants' acceptance of the program was also evaluated using a self-reported satisfaction scale. Self-efficacy, motivation, pain, and goal performance and satisfaction were secondary outcome measures. Adherence and acceptability were also measured. RESULTS: Fifteen participants (n = 15) completed the community-based exercise intervention and seventeen (n = 17) completed the education program. While no statistically significant differences were found, the EG experienced changes of moderate effect size in cardiorespiratory fitness, strength, motivation, and satisfaction with their goals. The EG attended, on average, two sessions per week. The community-based exercise intervention was highly accepted by and satisfying for participants to engage in. CONCLUSIONS: The EG had improvements in the two primary measures, cardiorespiratory fitness and musculoskeletal strength, following the intervention. The community-based exercise intervention was feasible and accepted by participants.

Impact of chemotherapy sequencing on local-regional failure risk in breast cancer patients undergoing breast-conserving therapy.

OBJECTIVE: This study was performed to evaluate long-term local-regional control rates after breast-conserving therapy (BCT) for patients undergoing surgery before or after neoadjuvant chemotherapy. METHODS: There were 2983 patients who underwent segmental mastectomy with whole-breast irradiation from 1987 to 2005. Clinicopathological and outcome data were reviewed, and comparisons were made between those undergoing surgery before and those undergoing surgery after neoadjuvant chemotherapy. RESULTS: There were 2331 patients (78%) who underwent surgery first and 652 (22%) received neoadjuvant chemotherapy. Patients receiving neoadjuvant chemotherapy had more advanced disease at baseline and more adverse clinicopathological features. The 5- and 10-year local-regional recurrence (LRR)-free survival rates were 97% [95% confidence interval (CI), 96-98) and 94% (95% CI, 93-95) for surgery first and 93% (95% CI, 91-95) and 90% (95% CI, 87-93) after neoadjuvant chemotherapy (P < 0.001). However, there were no differences in LRR-free survival rates when comparing the presenting clinical stage (P = NS). Of 607 patients presenting with clinical stage II/III disease, chemotherapy downstaged 313 patients (52%) to pathological stage 0/I disease; 294 (48%) had residual stage II/III disease. In multivariate analysis, an age less than 50 years, clinical stage III, grade 3, estrogen receptor (ER)-negative disease, estrogen receptor-positive disease without receipt of endocrine therapy, lymphovascular invasion, multifocal disease on pathology, and close/positive margins were associated with LRR. Use of neoadjuvant chemotherapy was not significant when added to the model. Adjusting for adverse factors, there were no differences in LRR between patients who underwent surgery before and those who underwent neoadjuvant chemotherapy after surgery. CONCLUSIONS: LRR after BCT is driven by tumor biology and disease stage. Appropriately selected patients can achieve high rates of local-regional control with BCT with either upfront surgery or surgery after neoadjuvant chemotherapy.

A technique to use CT images for in vivo detection and quantification of the spatial distribution of radiation-induced esophagitis.

The purpose of the study was to examine whether CT imaging can be used to quantify radiation-induced injury to the esophagus. Weekly CT images for 14 patients receiving proton therapy for thoracic tumors were retrospectively reviewed. The images were registered with the original treatment planning CT image using deformable registration techniques, and the esophageal contours from the treatment plan were automatically mapped to the weekly images. The relative change in the size of the esophagus was calculated for each CT slice as the ratio of the cross-sectional area of the esophagus (minus air) in the weekly CT image to the same area in the planning CT image. The maximum relative change in cross sectional area for each CT image was calculated and examined for correlation with the clinical toxicity score for all the patients. The average maximum relative expansion of the esophagus at the end of treatment was 1.41 ± 0.26, 1.68 ± 0.36, and 2.10 ± 0.18 for patients with grade 0, 2, and 3 esophagitis, respectively. An unpaired t-test, with the level of significance corrected with a Bonferroni correction, showed that the difference between grade 3 and 0 was significant, but the differences between grade 0 and 2, and 2 and 3 were not. The timing of changes in esophageal expansion closely matched that of clinically noted changes in patient symptoms. Expansion of the esophagus on CT images has potential as an objective measure of toxicity. The ability to quantify objectively the spatial distribution of radiation-induced injury will be a useful tool in understanding the impact of partial esophageal sparing on the probability of esophagitis.

Exploring the Perspectives of Adults Aging With Long-Term Physical Disabilities on Physical Activity: A Qualitative Study.

BACKGROUND: Adults aging with long-term physical disabilities (AAwPD) face personal and environmental barriers to living independently, but little is known about their perspectives on and experiences with physical activity (PA). PURPOSE: The purpose of this study was to explore the perspectives of AAwPD on PA. RESEARCH DESIGN: Qualitative semi-structured interviews with AAwPD were conducted virtually via phone or videoconference. STUDY SAMPLE: A convenience sample of AAwPD aged 45-65 and living with a physical disability for at least 5 years was recruited through aging organizations, disability organizations, and social media in St. Louis, Missouri until thematic saturation was reached (n = 20). DATA COLLECTION AND ANALYSIS: Participants were asked semi-structured interview questions about their perspectives and experiences with PA following an interview guide developed by disability, aging, and qualitative research experts. Data were analyzed using text analysis in NVivo 12. Codes were developed into themes by the research team and validated using member checking methods. RESULTS: Four themes emerged from the data: barriers and facilitators to engaging in PA, motivations and beliefs regarding PA, benefits of PA, and PA routines and habits. Participants reported a desire to engage in more PA but described barriers such as pain and fatigue symptoms, secondary health conditions, lack of social support, and fear of falling. Accessibility of facilities and equipment (eg, lack of ramps or equipment not at wheelchair height) and transportation barriers (eg, inconvenient schedules or excessive wait times) were specifically described as major environmental barriers. CONCLUSION: Most participants' reported PA routines did not meet the quantity or intensity levels recommended by current guidelines. These results may help inform healthcare providers, community programs, and future interventions to improve PA levels for AAwPD, an underserved but growing demographic.

Local-regional control according to surrogate markers of breast cancer subtypes and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast conserving therapy.

INTRODUCTION: Breast cancers of different molecular subtypes have different survival rates. The goal of this study was to identify patients at high risk for local-regional recurrence according to response to neoadjuvant chemotherapy and surrogate markers of molecular subtypes in patients undergoing breast conserving therapy (BCT). METHODS: Clinicopathologic data from 595 breast cancer patients who received neoadjuvant chemotherapy and BCT from 1997 to 2005 were identified. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression determined by immunohistochemistry were used to construct the following subtypes: ER+ or PR+ and HER2- (hormone receptor (HR)+/HER2-; 52%), ER+ or PR+ and HER2+ (HR+/HER2+; 9%), ER- and PR- and HER2+ (HR-/HER2+; 7%) and ER- and PR- and HER2- (HR-/HER2-; 32%). Actuarial rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards models were used for multivariate analysis (MVA). RESULTS: After a median follow-up of 64 months, the five-year local-regional recurrence (LRR)-free survival rate for all patients was 93.8%. The five-year LRR-free survival rates varied by subtype: HR+/HER2- 97.0%, HR+/HER2+ 95.9%, HR-/HER2+ 86.5% and HR-/HER2- 89.5% (P = 0.001). In addition to subtype, clinical stage III disease (90% vs. 95% for I/II, P = 0.05), high nuclear grade (92% vs. 97% with low/intermediate grade, P = 0.03), presence of lymphovascular invasion (LVI) (89% vs. 95% in those without LVI, P = 0.02) and four or more positive lymph nodes on pathologic examination (87% vs. 95% with zero to three positive lymph nodes, P = 0.03) were associated with lower five-year LRR-free survival on univariate analysis. On MVA, HR-/HER2+ and HR-/HER2- subtypes and disease in four or more lymph nodes were associated with decreased LRR-free survival. A pathologic complete response (pCR) was associated with improved LRR-free survival. CONCLUSIONS: Patients with HR+/HER2- and HR+/HER2+ subtypes had excellent LRR-free survival regardless of tumor response to neoadjuvant chemotherapy. Patients with HR-/HER2+ and HR-/HER2- subtypes with poor response to neoadjuvant chemotherapy had worse LRR-free survival after BCT. Additional study is needed to determine the impact of trastuzumab on local-regional control in HER2+ tumors. Our data suggest that patients with HR-/HER2- subtype tumors not achieving pCR may benefit from novel strategies to improve local-regional control.

Occult axillary lymph node metastases do not have prognostic significance in early stage breast cancer.

BACKGROUND: Axillary lymph node status is one of the most powerful prognostic indicators in patients with breast cancer and has implications for adjuvant treatment. It has been demonstrated that enhanced histologic evaluation of axillary lymph nodes, including serial sectioning of paraffin tissue blocks and immunohistochemical (IHC) staining, increases the rate of detection of occult metastases. The clinical significance of occult lymph node metastases has been the subject of debate. METHODS: In the current study, the authors identified 267 patients who underwent axillary lymph node dissection (ALND) between 1987 and 1995 and were lymph node negative according to a routine pathologic evaluation, which included the complete submission of all lymph nodes and an examination of 1 hematoxylin and eosin (H&E)-stained section per paraffin block. Patients did not receive systemic chemotherapy or hormone therapy. All of the dissected lymph nodes from these patients were re-evaluated by intensified pathologic methods (serial sectioning with H&E levels plus IHC). Occult metastases were categorized by detection method and size. The clinical significance of the occult metastases was determined. RESULTS: Thirty-nine patients (15%) who had lymph node-negative results on routine evaluation of their ALND specimens had occult metastases identified. Eight of these patients (20%) had macrometastases >2.0 mm, 15 (40%) had micrometastases (range, >0.2 mm to ≤2 mm), and 16 (40%) had isolated tumor cells (≤0.2 mm). The presence of occult metastases and the size of metastases did not affect recurrence-free or overall survival. CONCLUSIONS: The presence of occult metastasis did not have clinical significance in this cohort of patients with early stage breast cancer.

Evaluation of the MD Anderson Prognostic Index for local-regional recurrence after breast conserving therapy in patients receiving neoadjuvant chemotherapy.

BACKGROUND: We previously developed a prognostic index for assessing local-regional recurrence (LRR) risk in patients undergoing breast conservation therapy (BCT) after neoadjuvant chemotherapy. The prognostic index assigns a point for each of the following variables: clinical N2/N3 disease, lymphovascular invasion, residual pathologic tumor size >2 cm, and multifocal residual disease on pathology. The current study was undertaken to evaluate this prognostic index in an independent cohort. METHODS: We identified 551 patients treated from 2001 to 2005 with neoadjuvant chemotherapy, mastectomy or BCT, and radiation. These patients were not used in the original development of the prognostic index. Outcomes were stratified by prognostic index. The 5-year LRR-free survival was calculated using the Kaplan-Meier method, and differences were compared using the log-rank test. RESULTS: For patients undergoing BCT, the 5-year LRR-free survival rates were 92, 92, 84, and 69% when the prognostic index was 0 (n = 91), 1 (n = 82), 2 (n = 38), or 3-4 (n = 13) (P = 0.01). The 5-year LRR-free survival rates were similar between patients undergoing mastectomy or BCT when the prognostic index score was 0, 1, or 2. When the prognostic index score was 3-4, the 5-year LRR-free survival was significantly lower for patients treated with BCT compared with mastectomy (69 vs. 93%, P = 0.007). CONCLUSION: The previously developed prognostic index was successful in stratifying patients with respect to LRR in an independent cohort undergoing BCT after neoadjuvant chemotherapy. The prognostic index can be used to identify patients at high risk for LRR who may be considered for more extensive surgery or enrollment into clinical trials evaluating novel strategies for local-regional control.

American College of Surgeons Oncology Group (ACOSOG) Z0011: impact on surgeon practice patterns.

INTRODUCTION: The ACOSOG Z0011 trial has been described as practice-changing. The goal of this study was to determine the impact of the trial on surgeon practice patterns at our institution. METHODS: This is a review of practice patterns comparing the year before release of Z0011 to the year after an institutional multidisciplinary meeting discussing the results. Patients meeting Z0011 inclusion criteria were identified. Clinicopathologic data were compared between the cohorts. RESULTS: There were 658 patients with clinical T1-2 tumors planned for breast conservation: 335 in the pre-Z0011 cohort and 323 post-Z0011. Sixty-two (19 %) patients were sentinel lymph node (SLN) positive in the pre-Z0011 group versus 42 (13 %) post-Z0011 (p = 0.06). Before Z0011, 85 % (53/62) of SLN-positive patients underwent axillary node dissection (ALND) versus 24 % (10/42) after Z0011 (p < 0.001). After Z0011, surgeons were more likely to perform ALND on patients with larger tumors (2.2 vs. 1.5 cm, p = 0.09), lobular histology (p = 0.01), fewer SLNs (1 vs. 3, p = 0.09), larger SLN metastasis size (4 vs. 2.5 mm, p = 0.19), extranodal extension present (20 vs. 6 %, p = 0.16), or a higher probability of positive non-SLNs (p = 0.03). Surgeons were less likely to perform intraoperative nodal assessment post-Z0011 (26 vs. 69 %, p < 0.001) resulting in decreased median operative times for SLN-negative patients (79 vs. 92 min, p < 0.001). CONCLUSIONS: Surgeons at our institution have implemented Z0011 results for the majority of patients; however, clinicopathologic factors still impact the decision to perform ALND. Z0011 results have significantly impacted practice by decreasing rates of ALND, use of intraoperative nodal evaluation, and operative times.

Mobility Disability and Exercise: Health Outcomes of an Accessible Community-Based Center.

Objective: The purpose of this study was to determine how support and guidance provided by trained professionals during a 12-week, community-based transition exercise program, impact health outcomes and continued engagement in physical activity for persons with a mobility disability (PwMD). Design: A single arm pre-post design was used. Setting: Accessible community-based health and wellness center. Participants: The study included 244 PwMD using a mobility device. Interventions: Participants completed a 12-week transition exercise program provided through an accessible community facility that provided education and support to complete endurance and strength related exercises as well as programming to encourage transition to self-directed engagement in exercise. Main Outcome Measures: Bodyweight, BMI, pain, perceived exertion, speed, and distance during cardiovascular fitness testing, and strength were measured pre and post exercise program. The number of participants that signed up for a monthly membership after the program was also monitored. Results: For the total group, average pain reported over previous 30 days decreased significantly (p < 0.01), current daily pain decreased significantly (p < 0.05), perceived exertion at the end of the 9-min endurance test decreased significantly (p < 0.05), and the four upper extremity strength exercises showed large, significant strength gains (p < 0.01) after the program. There was no significant change in bodyweight, BMI, or speed and distance completed during endurance testing. At the completion of the program, 76% of participants enrolled in a monthly membership at the facility with the intentions to continue to exercise regularly. Conclusions: This study provides evidence that an accessible community-based exercise program, with a transitional component supported by trained professionals, can support the exercise goals of PwMD and improve strength, decrease pain, and may promote regular exercise adoption for PwMD.

An observational study of personal and environmental factors associated with attendance at a community-based adaptive fitness center for adults with physical disabilities.

BACKGROUND: Regular exercise has many benefits for adults with physical disabilities (AwPD). Despite these benefits, significant barriers to participating in exercise exist for AwPD. Community-based adaptive fitness centers promote exercise for AwPD by minimizing barriers. Research has yet to clearly examine the personal and environmental factors associated with enrollment and attendance rates of AwPD in community-based adaptive fitness centers. OBJECTIVE: The purpose of our study was to explore personal and environmental factors associated with AwPD and their attendance at a community-based adaptive fitness center once enrolled. METHODS: Individuals aged 18-85 with a physical disability interested in exercising were referred to a community-based adaptive fitness center. At initial assessment, participants completed demographics, health, barriers to exercise, and exercise self-efficacy (ESE) surveys. Following initial assessment, participant visits to the fitness center were tracked for six months. RESULTS: Of 106 participants, 27 never visited the facility after initial assessment, and the remaining participants with six months of attendance data (n = 67) averaged 14.9 (SD = 14.2) visits. Correlation results showed a negative curvilinear relationship between number of visits and years living with disability (rs = -0.24, p < 0.05), with higher attendance associated with more recent diagnosis. Logistic and stepwise regressions showed that ESE score (ß = 0.107, p = 0.026) was the only significant predictor of attending the fitness center once enrolled. CONCLUSIONS: This study demonstrates the importance of understanding personal and environmental factors and assessing ESE for AwPD who are newly enrolled in a community-based adaptive fitness center.

Novel PTH Gene Mutations Causing Isolated Hypoparathyroidism.

CONTEXT: Parathyroid hormone (PTH) gene mutations represent a rare cause of familial isolated hypoparathyroidism (FIH). These defects can cause hypoparathyroidism with increased or decreased serum levels of PTH through 1) impaired PTH synthesis; 2) induction of parathyroid cell apoptosis; or 3) secretion of bioinactive PTH molecules. Eight pathogenic mutations of this gene have been described previously. OBJECTIVE: Through describing 2 novel mutations of the PTH gene, we aim to extend the molecular basis for FIH and further refine the proposed mechanisms by which PTH mutations cause hypoparathyroidism. METHODS: Proband case reports were compiled with extended family analysis. The probands in both kindreds presented before age 10 days with hypocalcemia and elevated phosphate levels. Proband A had low PTH levels, whereas these levels were elevated in Proband B. Proband B was initially diagnosed with pseudohypoparathyroidism. Methylation analysis was performed of CpG dinucleotides within 3 GNAS differentially methylated regions; whole-genome sequencing; and PTH infusion with analysis of nephrogenous 3',5'-cyclic adenosine 5'-monophosphate. RESULTS: Proband A had a novel heterozygous sequence change in exon 2 of the PTH gene, c.46_47delinsAA (p.Ala16Lys), and proband B had a novel homozygous nucleotide transition in PTH exon 3 (c.128G > A; p.G43E) that led to replacement of glycine by glutamic acid at position 12 of PTH 1-84. PTH 1-34 infusion demonstrated that renal responsiveness to PTH was intact and not antagonized by circulating bioinactive PTH. CONCLUSION: PTH gene mutations are uncommon causes of hypoparathyroidism, but can be misdiagnosed as disorders of gland development or receptor function if PTH levels are decreased or elevated, respectively. Genetic testing should be considered early in the diagnostic approach to these presentations.

Recruitment and retention of scholarship recipient nursing students and staff.

Few problems are more relevant in health care today than nurse recruitment and retention. The purpose of this study was to identify job satisfaction factors for nurse and nursing student education scholarship recipients, as well as examine the relationship of these factors to the intent to complete contractual agreements. Findings revealed that job satisfaction and a positive image of nursing were influential factors in intent to complete contractual agreements. Results may prove valuable information to recruit nursing students and increase job satisfaction.