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.

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.

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.

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.

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.

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.

Community-based exercise goals of persons with spinal cord injury: Interpreted using the International Classification of Functioning, Disability, and Health.

OBJECTIVE: To identify goals for exercising among community-dwelling persons with spinal cord injury (PwSCI). DESIGN: Qualitative descriptive study. SETTING: Community-based exercise facility for persons with a disability. PARTICIPANTS: Fifty-five PwSCI identified their exercise goals prior to participation in a community-based exercise intervention. INTERVENTIONS: None. OUTCOME MEASURES: A modified version of the Canadian Occupational Performance Measure was used to ask about exercise goals. The International Classification of Functioning, Disability, and Health (ICF) was used to code the goals for themes. RESULTS: The participants were predominantly male (76%) and Black (56%) with thoracic-level injury (51%) and a mean age of 39.44 (standard deviation [SD] 13.62). A total of 231 goals (mean 4.2 goals per participant; SD 1.25) were identified. Participants rated their performance and satisfaction with their goals as 4.256 (SD 1.55) and 3.57 (SD 1.67), respectively. Participants most frequently reported goals related to endurance, muscle strengthening, weight loss, activities of daily living, transferring, and home and community mobility. The most commonly reported goals fell into five ICF domains: Functions of Cardiovascular, Hematological, Immunological, and Respiratory Systems; Neuromusculoskeletal and Movement-Related Functions; Structures Related to Movement; Mobility; and Self-Care. CONCLUSION: PwSCI have goals they would like to achieve through participation in exercise. The goals are multifaceted and encompass improving health and fitness as well as improving performance in everyday activities such as transferring and mobility. Identifying themes of goals for PwSCI to achieve through exercise is an important step in developing programs and interventions needed to support PwSCI living in the community.

Successful embolization of a renal arteriovenous fistula; a feared kidney biopsy complication.

The authors report a case of a 57-year-old woman who was successfully treated with a percutaneous embolization procedure for a renal arteriovenous fistula that developed as a complication of a kidney biopsy. An acute kidney injury that failed to resolve with medical management prompted further investigation with a renal biopsy. Five hours after the kidney biopsy, the patient became hemodynamically unstable with a blood pressure of 77 of 52 mm Hg. A stat abdominal computed tomography scan without contrast discovered a large left-sided perinephric hematoma that measured up to 11.5 cm with a moderate amount of perinephric blood. An angiogram subsequently demonstrated the presence of an arteriovenous fistula at the inferior pole of the left kidney. Several 2 × 3 mm and 3 × 3 mm coils were deployed into two separate segmental branches of the inferior pole, and the post embolization angiogram confirmed resolution of the previously visualized arteriovenous fistula.

Excess epicardial fat volume in women is a novel risk marker for microvascular dysfunction, which may be a contributing factor in the atypical chest pain syndrome.

BACKGROUND: Excess epicardial fat volume (EFV) has been recently implicated in cardiovascular structural and functional abnormalities. It has been associated with abnormal microvascular stiffness (as reflected by radial artery waveform; C2), which may result in microvascular dysfunction and contribute to the atypical chest pain syndrome without obstructive coronary artery disease (CAD). Women have been statistically shown to present with atypical chest pain more often than men and specifically without obstructive CAD. The aim of this study is to assess whether excess EFV in female subjects is associated with significant microvascular dysfunction (i.e., C2), in subjects without obstructive CAD. RESULTS: We screened 596 asymptomatic subjects, ages 20-79, using the Early Cardiovascular Health Risk Scoring System (ECVHRS), which has been reported. Out of the 596 total subjects, 230 subjects had a CACS. Out of these 230 subjects, 77 subjects (45 females; 32 males) had a 0 CACS. The 45 females from this cohort were the subjects of this study, and they were further categorized into 3 groups: group 1 (normal EFV, non-obese female subjects; n=16), females with ECVHRS < 3 and ACC/AHA risk score < 5%; group 2 (n = 9), females with elevated EFV and no abdominal visceral obesity; and group 3 (n=20), females with elevated EFV and abdominal visceral obesity. The average EFV was determined to be 72±20 cm3 among group 1, which indicates the values for normal EFV. The results in group 2 indicate that excess EFV is contributing to the development of microvascular dysfunction, resulting in abnormal micro-arterial (C2) elasticity (p< 0.00001), increase in resting blood pressure (p =0.0001), an abnormal rise in blood pressure (BP) at rest and post-mild protocol exercise (PME) (p = < 0.00001), and abnormal increase in carotid intima-media thickness (CIMT) (p = 0.000164). CONCLUSION: Excess EFV appears to be not only a novel cardiovascular risk marker, but also the culprit for other cardiovascular risk markers. Based on these findings, elevated EFV may contribute to the development of the atypical chest pain syndrome in females without obstructive CAD. Additionally, EFV is emerging as a potential clinically relevant significant cardiovascular risk biomarker and may become a target to reduce cardiovascular morbidity and mortality.

A Phenotypic Female Adolescent with Primary Amenorrhea and Dysmorphic Features.

We report on a case of a 14-year-old phenotypic female with a microdeletion at 13q31.1-q31.3, dysmorphic facial and limb features, and neurologic symptoms. She presented to her pediatrician with concerns for delayed puberty, and laboratory analysis revealed hypergonadotropic hypogonadism. She was found to have an XY karyotype and streak gonads. Further genetic studies did not reveal another cause for her gonadal dysgenesis and, to our knowledge, an association with her known 13q-microdeletion has not yet been reported. Given the risk of malignancy with XY gonadal dysgenesis, the patient had surgery to remove the gonads and had no postoperative complications after a 6-month follow-up visit. We also discuss the role of the pediatrician in cases of delayed puberty, from initial diagnosis to definitive management. [Pediatr Ann. 2019;48(12):e495-e500.].

Exercise testing protocol using a roller system for manual wheelchair users with spinal cord injury.

OBJECTIVE: Determine the validity and reliability of an exercise testing protocol to evaluate cardiorespiratory measures in manual wheelchair users (MWUs) with spinal cord injury (SCI) using a roller-based (RS) wheelchair system. DESIGN: Repeated measures within-subject design. SETTING: Community-based research laboratory. PARTICIPANTS: Ten adults with SCI requiring the use of a manual wheelchair. INTERVENTIONS: Not applicable. OUTCOME MEASURES: Cardiorespiratory measures (peak oxygen consumption [VO2peak], respiratory exchange ratio [RER], pulmonary ventilation [VE], energy expenditure [EE], heart rate [HR], accumulated kilocalories [AcKcal]) and perceived exertion (RPE) were measured during three separate maximal exercise tests using an arm crank ergometer (ACE) and an RS. RESULTS: At maximal exertion, there were no significant differences in variables between groups, with moderate-to-strong correlations (P < 0.05, r = 0.79-0.90) for VO2, HR, RPE, AcKcal, and rate of EE between RS and ACE trials. Significant moderate-to-strong correlations existed between RS trials for VO2, AcKcal, rate of EE, and peak power output (P < 0.01, r = 0.77-0.97). CONCLUSIONS: VO2peak was highly correlated between ACE and RS trials and between the two RS trials, indicating the RS protocol to be reliable and valid for MWUs with SCI. Differences in perceived exertion and efficiency at submaximal workloads and maximal pulmonary ventilation at peak workloads indicated potential advantages to using the RS.

Validation of Effective Dose as a Better Predictor of Radiation Pneumonitis Risk Than Mean Lung Dose: Secondary Analysis of a Randomized Trial.

PURPOSE: To confirm the superiority of effective dose (Deff) over mean lung dose (MLD) for predicting risk of radiation pneumonitis (RP), using data from patients on a randomized trial of intensity modulated radiation therapy (IMRT) versus passively scattered proton therapy (PSPT). METHODS AND MATERIALS: The prescribed target dose for the 203 evaluated patients was 66 to 74 Gy (relative biological effectiveness) in 33 to 37 fractions with concurrent carboplatin/paclitaxel. Time to grade ≥2 RP was computed from the start of radiation therapy, with disease recurrence or death considered censoring events. Generalized Lyman models of censored time to RP were constructed with MLD or Deff as the dosimetric parameter. Smoking status (current, former, never) was also analyzed. RESULTS: Of the 203 patients, 46 experienced grade ≥2 RP (crude incidence 23%) at a median 3.7 months (range, 0.6-12.6 months). The volume parameter estimated for the Deff model was n = 0.5, confirming estimates from earlier studies. Compared with MLD (in which n = 1), the dosimetric parameter Deff, computed using n = 0.5, resulted in a better fit of the Lyman model to the clinical data (P = .010). Using Deff, the model describes RP risk for IMRT and PSPT data combined because no further improvement was found from separate fits (P = .558). Based on Deff, predicted RP risk per patient ranged from 24 percentage points lower to 19 percentage points higher than predictions based on MLD. For patients with similar MLD, Deff predicted higher risk, on average, for PSPT over IMRT. Current smokers had a lower risk of RP compared with former smokers and nonsmokers (P = .021). CONCLUSIONS: We used data from a randomized trial to validate our previous finding that Deff with n = 0.5 (corresponding to root mean squared dose) is a better predictor of RP than is MLD. Differences between Deff and MLD indicate that delivering higher doses to smaller lung volumes (vs lower doses to larger volumes) increases RP risk. We further corroborated that current smoking is associated with decreased RP risk.

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.

A motor learning approach to training wheelchair propulsion biomechanics for new manual wheelchair users: A pilot study.

CONTEXT/OBJECTIVE: Developing an evidence-based approach to teaching wheelchair skills and proper propulsion for everyday wheelchair users with a spinal cord injury (SCI) is important to their rehabilitation. The purpose of this project was to pilot test manual wheelchair training based on motor learning and repetition-based approaches for new manual wheelchair users with an SCI. DESIGN: A repeated measures within-subject design was used with participants acting as their own controls. METHODS: Six persons with an SCI requiring the use of a manual wheelchair participated in wheelchair training. The training included nine 90-minute sessions. The primary focus was on wheelchair propulsion biomechanics with a secondary focus on wheelchair skills. OUTCOME MEASURES: During Pretest 1, Pretest 2, and Posttest, wheelchair propulsion biomechanics were measured using the Wheelchair Propulsion Test and a Video Motion Capture system. During Pretest 2 and Posttest, propulsion forces using the WheelMill System and wheelchair skills using the Wheelchair Skills Test were measured. RESULTS: Significant changes in area of the push loop, hand-to-axle relationship, and slope of push forces were found. Changes in propulsion patterns were identified post-training. No significant differences were found in peak and average push forces and wheelchair skills pre- and post-training. CONCLUSIONS: This project identified trends in change related to a repetition-based motor learning approach for propelling a manual wheelchair. The changes found were related to the propulsion patterns used by participants. Despite some challenges associated with implementing interventions for new manual wheelchair users, such as recruitment, the results of this study show that repetition-based training can improve biomechanics and propulsion patterns for new manual wheelchair users.

Impact of heart and lung dose on early survival in patients with non-small cell lung cancer treated with chemoradiation.

BACKGROUND AND PURPOSE: To determine whether the impact of heart dose on early overall survival (OS) reported in RTOG 0617 could be confirmed in an independent cohort. MATERIALS AND METHODS: Heart and lung dose-volume histogram data were retrospectively extracted for patients with stage IIIA-IIIB non-small cell lung cancer (NSCLC) who had received radiotherapy using 3D CRT, IMRT or proton therapy delivered with concurrent chemotherapy between 1999 and 2010. Potential associations between clinical and dosimetric factors and OS up to 24months after start of treatment were assessed in univariate and multivariate analyses with log-rank tests or Cox proportional hazards models. RESULTS: 468 patients met inclusion criteria. Factors associated with increased risk of early death in univariate analyses were performance status (PS), stage, treatment with 3D conformal radiotherapy, lower tumor dose and larger gross tumor volume (GTV), mean heart dose (MHD), heart V5, mean lung dose (MLD) and lung V5. Factors retaining significance in multivariate analysis were PS, GTV, and MLD. There was a strong correlation between MHD and heart V5 with MLD. However, no evidence was found that heart doses had an independent effect on OS during the first 2years. CONCLUSIONS: In a large group of patients treated with chemoradiation for locally advanced NSCLC, heart dose was not found to be associated with early survival outcomes when lung dose was taken into account. Nevertheless, based on the known adverse effects of radiotherapy on vasculature and cardiac function, dose to the heart should be minimized during radiotherapy planning.

The Neo-Bioscore Update for Staging Breast Cancer Treated With Neoadjuvant Chemotherapy: Incorporation of Prognostic Biologic Factors Into Staging After Treatment.

IMPORTANCE: We previously described and validated a breast cancer staging system (CPS+EG, clinical-pathologic scoring system incorporating estrogen receptor-negative disease and nuclear grade 3 tumor pathology) for assessing prognosis after neoadjuvant chemotherapy using pretreatment clinical stage, posttreatment pathologic stage, estrogen receptor (ER) status, and grade. Development of the CPS+EG staging system predated routine administration of trastuzumab in patients with ERBB2-positive disease (formerly HER2 or HER2/neu). OBJECTIVE: To validate the CPS+EG staging system using the new definition of ER positivity (≥1%) and to develop an updated staging system (Neo-Bioscore) that incorporates ERBB2 status into the previously developed CPS+EG. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of data collected prospectively from January 2005 through December 2012 on patients with breast cancer treated with neoadjuvant chemotherapy at The University of Texas MD Anderson Cancer Center. MAIN OUTCOMES AND MEASURE: Prognostic scores were computed using 2 versions of the CPS+EG staging system, one with ER considered positive if it measured 10% or higher, the other with ER considered positive if it measured 1% or higher. Fits of the Cox proportional hazards model for the 2 sets of prognostic scores were compared using the Akaike Information Criterion (AIC). Status of ERBB2 was added to the model, and the likelihood ratio test was used to determine improvement in fit. RESULTS: A total of 2377 patients were included; all were women (median age, 50 years [range, 21-87 years]); ER status was less than 1% in 28.9%, 1% to 9% in 8.3%, and 10% or higher in 62.8%; 591 patients were ERBB2 positive. Median follow-up was 4.2 years (range, 0.5-11.7 years). Five-year disease-specific survival was 89% (95% CI, 87%-90%). Using 1% or higher as the cutoff for ER positivity, 5-year disease-specific survival estimates determined using the CPS+EG stage ranged from 52% to 98%, thereby validating our previous finding that the CPS+EG score facilitates more refined categorization into prognostic subgroups than clinical or final pathologic stage alone. The AIC value for this model was 3333.06, while for a model using 10% or higher as the cutoff for ER positivity, it was 3333.38, indicating that the model fits were nearly identical. The improvement in fit of the model when ERBB2 status was added was highly significant, with 5-year disease-specific survival estimates ranging from 48% to 99% (P < .001). Incorporating ERBB2 into the staging system defined the Neo-Bioscore, which provided improved stratification of patients with respect to prognosis. CONCLUSIONS AND RELEVANCE: The Neo-Bioscore improves our previously validated staging system and allows its application in ERBB2-positive patients. We recommend that treatment response and biologic markers be incorporated into the American Joint Committee on Cancer staging system.

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.

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.