Identification Of A Higher Risk Lymphedema Phenotype And Associations With Cytokine Gene Polymorphisms.

CONTEXT: Breast cancer-related lymphedema (BCRL) is chronic condition that occurs in 5% to 75% of women following treatment for breast cancer. However, little is known about the risk factors and mechanisms associated with a worse BCRL profile. OBJECTIVES: Identify distinct BCRL profiles in women with the condition (i.e., lower vs. higher risk phenotype) and evaluate for associations with pro- and anti-inflammatory genes. METHODS: Latent class profile analysis (LCPA) was used to identify the BCRL profiles using phenotypic characteristics evaluated prior to surgery. Candidate gene analyses were done to identify cytokine genes associated with the two BCRL profiles. RESULTS: Of the 155 patients evaluated, 35.5% (n = 55) were in the Lower and 64.5% (n = 100) were in the Higher Risk classes. Risk factors for membership in the Higher class included: lower functional status, having sentinel lymph node biopsy, axillary lymph node dissection, mastectomy, higher number of positive lymph nodes, and receipt of chemotherapy. Polymorphisms for interleukin (IL)1-beta and IL6 were associated with membership in the Higher Risk class. CONCLUSION: The readily available and clinically relevant phenotypic characteristics associated with a worse BCRL profile can be used by clinicians to identify higher risk patients. If confirmed, these characteristics can be tested in predictive risk models. In addition, the candidate gene findings may guide the development of mechanistically-based interventions to decrease the risk of BCRL.

Predictive factors of academic success in neuromusculoskeletal anatomy among doctor of physical therapy students.

Predictors of academic success in anatomy have been studied, but not in Doctor of Physical Therapy (DPT) students. The objectives of this study were to (1) explore predictors of academic success in a DPT anatomy course, (2) evaluate sex-based differences in the predictors of academic success and their influence on anatomy course grade, and (3) investigate the influence of the DPT anatomy course on visual-spatial ability. Forty-nine DPT students completed a demographic questionnaire, Learning and Study Strategies Inventory (LASSI), and Mental Rotations Test (MRT) before the ten-week anatomy course (MRT-1) and repeated the MRT at the end of the course (MRT-2). Anatomy course grade was determined based on quizzes and written and practical examinations. Multiple regression analysis showed significant associations between the predictor variables age (p = 0.010) and the LASSI anxiety subscale (p = 0.017), which measures anxiety coping, with the anatomy course grade. On the MRT-1, male DPT students attempted and correctly answered more questions than females (both, p < 0.0001). Female students had higher LASSI self-regulation and use of academic resources subscale scores (both, p < 0.05). In the 44 DPT students that completed the MRT-2, the number of correct and attempted responses increased following the anatomy course (p < 0.0001). Age and anxiety coping, but not sex, are predictors of anatomy course grades in DPT students. Mental rotations test scores improved following the anatomy course. The LASSI should be used in other cohorts to identify students with low anxiety subscale scores in order to provide targeted support.

Polymorphisms in Cytokine Receptor and Regulator Genes are Associated with Levels of Exercise in Women Prior to Breast Cancer Surgery.

Background: Little is known about the genetic characteristics associated with exercise in women undergoing breast cancer surgery. Purpose: In a sample of women who were evaluated prior to breast cancer surgery (n = 310), we evaluated for differences in demographic and clinical characteristics between patients who did and did not exercise on a regular basis and evaluated for associations between polymorphisms in genes for pro- and anti-inflammatory cytokines, their receptors, and their transcriptional regulators. Methods: Patients completed an investigator-developed exercise questionnaire. Based on the recommended level of exercise (≥150 minutes/week), survivors were classified into no exercise (NoEx), less exercise (LessEx), or recommended exercise (RecEx) groups. Candidate gene analyses were done to identify relationships between polymorphisms and exercise group membership (i.e., NoEx vs. RecEx). Only 23.5% of the total sample met the recommendations for regular exercise. Results: Compared to the RecEx group (n = 78), patients in the NoEx group (n = 120) had less education; were less likely to report being White or Asia/Pacific Islander; more likely to report a lower household income; had a higher body mass index (BMI), had a poorer functional status; had a higher comorbidity burden; were more likely to self-report high blood pressure; and were more likely to have received neoadjuvant chemotherapy. Polymorphisms in IFNGR1 and NFKB1 were associated with membership in the NoEx group. Conclusions: While they warrant replication, our findings suggest that variations in cytokine-related genes may play a role in exercise behavior, and that clinicians need to assess for barriers to regular exercise and educate patients on its benefits.

Assessment of Arm Volume Using a Tape Measure Versus a 3D Optical Scanner in Survivors with Breast Cancer-Related Lymphedema.

Background: Lymphedema (LE) is a significant clinical problem for breast cancer survivors. While the water displacement test and circumferential assessment using a tape measure (TM) are common methods to assess differences in arm volumes, faster and more reliable methods are needed. Study purposes, in breast cancer survivors (n = 294), were to compare the average total arm volumes and interlimb volume ratios for women with and without a history of LE, using a TM and three-dimensional (3D), whole-body surface scanner (3D scan); compare the level of agreement between arm volumes and interlimb volume ratios obtained using the two devices; and evaluate the percent agreement between the two measures in classifying cases of LE using three accepted thresholds. Methods and Results: Measurements were done using a spring-loaded TM and Fit3D ProScanner. Paired t-tests and Bland-Altman analyses were used to achieve the study aims. For circumference and volume comparisons, compared with the 3D scan, values obtained using the TM were consistently smaller. In terms of level of agreement, the Bland-Altman analyses demonstrated large biases and wide limits of agreement for the calculated arm volumes and volume ratios. In terms of the classification of caseness, using the 200-mL interlimb volume difference criterion resulted in 81.6% overall agreement; using the >10% volume difference between the affected and unaffected arms resulted in 78.5% overall agreement; and using the volume ratio ≥1.04 criterion resulted in 62.5% overall agreement. For all three accepted threshold criteria, the percentage of cases was significantly different between the TM and 3D scan techniques. Conclusions: The 3D technology evaluated in this study has the potential to be used for self-initiated surveillance for LE. With improvements in landmark identification and software modifications, it is possible that accurate and reliable total arm volumes can be calculated and used for early detection.

Use of Dual-Energy X-Ray Absorptiometry to Assess Soft Tissue Composition in Breast Cancer Survivors With and Without Lymphedema.

Background: In patients with lymphedema (LE), in addition to hand dominance, between-group comparisons of interlimb soft tissue differences need to account for differences in whole-body adiposity, measured directly by dual energy X-ray absorptiometry (DXA) or indirectly by body mass index. No study has evaluated the effects of hand dominance and whole-body adiposity on limb composition in patients with LE. This study's purpose was to compare soft tissue composition of affected and unaffected limbs of women with breast cancer, who did and did not have LE, controlling for dominance and percent body fat. Methods and Results: Whole-body DXA scans were acquired and included measures of percent body fat, upper limb total mass, upper limb fat mass, and upper limb fat-free mass. Participants were classified into one of three groups: women without LE; women with only subjective LE; and women with objective signs of LE at the time of assessment. Differences among the LE groups were evaluated using analysis of variance (ANOVA) and Chi-square analyses. Analysis of covariance (ANCOVA) was used to control for percent body fat and for the affected limb dominance. Compared to women without LE, women with objective signs of LE have greater total limb mass, fat mass, and fat-free mass in their affected limbs, independent of affected side dominance and percent body fat. In addition, the interlimb differences in total mass, fat mass, and fat-free mass were greater for the women with objective signs of LE, compared to the other two groups. Conclusions: DXA is useful in identifying soft tissue changes in patients with LE. Given that limb circumferences measure only changes in limb volume and that bioimpedance provides estimates of extracellular fluid, DXA has the advantage of being able to estimate the volumes of specific tissues in the limb.

Treatment of Breast Cancer-Related Lymphedema Using Negative Pressure Massage: A Pilot Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy of negative pressure massage treatment (NPMT) compared with manual lymphatic drainage (MLD) in women with chronic breast cancer-related lymphedema (LE). We hypothesized that NPMT would result in greater improvements in LE and upper limb function. DESIGN: Pilot single-blinded randomized controlled trial. SETTING: Health sciences university. PARTICIPANTS: Of 64 women screened, 28 met eligibility requirements (ie, >18y of age; completed active treatment for breast cancer; had unilateral arm LE for ≥1y; were not receiving LE care; had stable LE) and were randomized to the NPMT (n=15) and control groups (n=13). INTERVENTIONS: The intervention group received NPMT and the control group received MLD; both received twelve 60-minute sessions over 4-6 weeks. MAIN OUTCOME MEASURES: Bioimpedance (lymphedema index [L-Dex] units]), limb volume (mL) calculated from limb circumference, and Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) score. RESULTS: Outcomes were analyzed for 28 women. Compared to the MLD group, the NPMT group demonstrated greater improvement with a large effect size in L-Dex scores (P=.001; standardized mean difference [SMD]=-1.15; 95% confidence interval, -1.96 to -0.35) and interlimb volume differences (P=.038; SMD=-0.83; 95% confidence interval, -1.60 to -0.05). Differences in DASH scores were not statistically significant (P=.067). CONCLUSIONS: Compared to MLD, treatment with NPMT resulted in greater improvement in L-Dex scores and interlimb volume differences in women with a duration of unilateral upper limb LE of >1 year. Our findings need to be confirmed in a larger randomized controlled trial.

A Comparison of Supine Versus Stand-on Bioimpedance Devices to Assess Breast Cancer-Related Lymphedema.

Background: While supine bioimpedance devices are used to evaluate for lymphedema (LE), stand-on devices are gaining popularity. Because research on differences in bioimpedance values between the two devices is limited, this study's purposes were to: (1) determine the average upper limb impedance values and inter-limb ratios for women who self-reported having (n = 34) or not having (n = 61) a history of LE, using a single-frequency supine device and a multifrequency stand-on device; (2) compare the level of agreement in inter-limb impedance ratios between the two devices; evaluate the percent agreement between the two devices in classifying cases of LE using established supine thresholds; and evaluate the percent agreement in classifying cases of LE between the supine device using previously established supine thresholds and the stand-on device using two published standing thresholds. Methods and Results: Bioimpedance measures were done using the two devices. For the entire sample, absolute impedance values for both the affected and unaffected limbs were significantly higher for the stand-on device in women with and without LE. Impedance values for the two methods were highly correlated. Bland-Altman analysis determined that for the entire range of impedance ratios the values for the two devices could not be used interchangeably. Conclusions: Findings suggest that the stand-on device can be a useful and valid tool to assess for LE. However, because agreement is not perfect, values obtained from the two devices should not be used interchangeably to evaluate for changes in impedance ratios, particularly for ratios of >1.20.

Association Between Physical Activity Levels and Chemotherapy-Induced Peripheral Neuropathy Severity in Cancer Survivors.

OBJECTIVES: To evaluate for differences in demographic and clinical characteristics, as well as subjective and objective measures of chemotherapy-induced peripheral neuropathy (CIPN), among different exercise groups. SAMPLE & SETTING: Cancer survivors (N = 290) were recruited from throughout the San Francisco Bay Area. METHODS & VARIABLES: Based on the recommended 150 minutes or more of exercise per week, survivors were classified into the no exercise (NoEx), less exercise (LessEx), or recommended exercise (RecEx) group. Survivors completed self-report questionnaires and underwent sensory and balance testing. RESULTS: Compared to the RecEx group, survivors in the NoEx group had less education, were less likely to be married/partnered, had a lower household income, had a higher level of comorbidity, and had poorer functional status. No differences were found among the groups in CIPN duration; pain intensity scores; or changes in light touch, cold, and pain sensations. IMPLICATIONS FOR NURSING: Clinicians can recommend walking as a therapeutic option for survivors with CIPN and refer them to physical therapy.

Changes in Attentional Function in Patients From Before Through 12 Months After Breast Cancer Surgery.

CONTEXT: Although approximately 75% of patients with breast cancer report changes in attentional function, little is known about how demographic, clinical, symptom, and psychosocial adjustment (e.g., coping) characteristics influence changes in the trajectories of attentional function over time. OBJECTIVES: This study evaluated interindividual variability in the trajectories of self-reported attentional function and determined which demographic, clinical, symptom, and psychosocial adjustment characteristics were associated with initial levels and with changes in attentional function from before through 12 months after breast cancer surgery. METHODS: Before surgery, 396 women were enrolled. Attentional Function Index (AFI) was completed before and nine times within the first 12 months after surgery. Hierarchical linear modeling was used to determine which characteristics were associated with initial levels and trajectories of attentional function. RESULTS: Given an estimated preoperative AFI score of 6.53, for each additional month, the estimated linear rate of change in AFI score was an increase of 0.054 (P < 0.001). Higher levels of comorbidity, receipt of adjuvant chemotherapy, higher levels of trait anxiety, fatigue, and sleep disturbance, and lower levels of energy and less sense of control were associated with lower levels of attentional function before surgery. Patients who had less improvements in attentional function over time were nonwhite, did not have a lymph node biopsy, had received hormonal therapy, and had less difficulty coping with their disease. CONCLUSION: Findings can be used to identify patients with breast cancer at higher risk for impaired self-reported cognitive function and to guide the prescription of more personalized interventions.

Perceived stress is associated with a higher symptom burden in cancer survivors.

BACKGROUND: Although multiple co-occurring symptoms are a significant problem for cancer survivors, to the authors' knowledge little is known regarding the phenotypic characteristics associated with a higher symptom burden. The objectives of the current study were to evaluate the occurrence, severity, and distress associated with 32 symptoms and examine the phenotypic and stress characteristics associated with a higher symptom burden. METHODS: A total of 623 cancer survivors completed a demographic questionnaire, as well as measures of functional status, comorbidity, and global (Perceived Stress Scale) and cancer-related (Impact of Event Scale-Revised) stress. The Memorial Symptom Assessment Scale was used to evaluate symptom burden. Multiple linear regression analysis was used to determine the phenotypic characteristics associated with a higher symptom burden. RESULTS: The mean number of symptoms was 9.1 (±5.2). The most common, severe, and distressing symptoms were lack of energy, problems with sexual interest/activity, and hair loss, respectively. Poorer functional status, a higher level of comorbidity, and a history of smoking as well as higher Perceived Stress Scale and Impact of Event Scale-Revised scores were associated with a higher symptom burden. The overall model explained approximately 45.6% of the variance in symptom burden. CONCLUSIONS: Although cancer survivors report a high number of co-occurring symptoms of moderate severity and distress, in the current study, no disease or treatment characteristics were found to be associated with a higher symptom burden. Clinicians need to assess for general and disease-specific stressors and provide referrals for stress management interventions. Future studies need to examine the longitudinal relationships among symptom burden, functional status, and level of comorbidity, as well as the mechanisms that underlie the associations between stress and symptom burden.

Deleterious Effects of Higher Body Mass Index on Subjective and Objective Measures of Chemotherapy-Induced Peripheral Neuropathy in Cancer Survivors.

CONTEXT: Recent, albeit, limited evidence suggests that body mass index (BMI) may be a modifiable risk factor to reduce the deleterious effects of chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors. OBJECTIVES: To evaluate for differences in demographic, clinical, pain, sensation, and balance characteristics among three BMI groups. We hypothesized that as BMI increased, survivors would report higher pain intensity scores and have significant decrements in measures of sensation and balance. METHODS: A total of 416 survivors with CIPN were evaluated using subjective and objective measures of CIPN. Survivors were divided into three BMI groups (i.e., normal weight, overweight, and obese). Differences among the BMI groups were evaluated using parametric and nonparametric statistics. RESULTS: Of the 416 survivors, 45.4% were normal weight, 32.5% were overweight, and 22.1% were obese. Compared with the normal-weight group, survivors in the other two groups had lower functional status scores, a higher comorbidity burden, higher pain intensity scores, and higher interference scores. In addition, compared with the normal-weight group, survivors in the other two BMI groups had significantly worse balance scores. CONCLUSION: Our findings support the hypothesis that as BMI increased, pain sensation and balance characteristics worsened. Our findings suggest that nutritional counseling as well as exercise and weight management programs in survivors with CIPN may improve these clinically important problems.

Associations Between Catecholaminergic and Serotonergic Genes and Persistent Arm Pain Severity Following Breast Cancer Surgery.

Persistent arm pain is a common problem after breast cancer surgery. Little is known about genetic factors that contribute to this type of postsurgical pain. Study purpose was to explore associations between persistent arm pain phenotypes and genetic polymorphisms among 15 genes involved in catecholaminergic and serotonergic neurotransmission. Women (n = 398) rated the presence and intensity of arm pain monthly for 6 months after breast cancer surgery. Three distinct latent classes of patients were identified (ie, no arm pain [41.6%], mild arm pain (23.6%), and moderate arm pain (34.8%). Logistic regression analyses were used to evaluate for differences between genotype or haplotype frequencies and the persistent arm pain classes. Compared with the no arm pain class, 3 single nucleotide polymorphisms and 1 haplotype, in 4 genes, were associated with membership in the mild arm pain class: COMT rs4633, HTR2A haplotype B02 (composed of rs1923886 and rs7330636), HTR3A rs1985242, and TH rs2070762. Compared with the no arm pain class, 4 single nucleotide polymorphisms in 3 genes were associated with membership in the moderate arm pain class: COMT rs165656, HTR2A rs2770298 and rs9534511, and HTR3A rs1985242. Findings suggest that variations in catecholaminergic and serotonergic genes play a role in the development of persistent arm pain. PERSPECTIVE: Limited information is available on genetic factors that contribute to persistent arm pain after breast cancer surgery. Genetic polymorphisms in genes involved in catecholaminergic and serotonergic neurotransmission were associated with 2 persistent arm pain phenotypes. Findings may be used to identify patients are higher risk for this common pain condition.

Contribution of Loss of Large Fiber Function to Pain in 2 Samples of Oncology Patients.

OBJECTIVES: Numbness associated with neuropathic pain suggests the loss of function in myelinated, large diameter sensory neurons. The purpose of this study was to examine the relationships between pain severity and subjective (ie, severity of numbness) and objective (ie, loss of light touch sensations, vibration thresholds) measures of loss of large fiber function in adult survivors with chemotherapy-induced peripheral neuropathy (CIPN, n=426) and breast cancer patients with persistent postsurgical pain (n=80). MATERIAL AND METHODS: For both samples, average pain and numbness were evaluated using a 0 to 10 numeric rating scale. Loss of light touch sensations in the hands and feet of patients with CIPN and in the upper arm of patients at 5 and 6 months following breast cancer surgery were assessed using Semmes Weinstein monofilaments. Loss of vibration in the hands and feet of patients with CIPN was assessed using a biothesiometer. Pearson Product Moment correlation coefficients were calculated between average pain and the number or percentage of sites with loss of light touch sensations, mean vibration thresholds, and the severity of numbness. RESULTS: For both pain conditions, average pain scores were significantly correlated with objective measures of large fiber function (r=0.12 to 0.34; all P<0.05) and numbness (r=0.22 to 0.52; all P<0.008). DISCUSSION: Our findings, in 2 independent samples of oncology patients, suggest that loss of function of myelinated, large diameter fibers contributes to the severity of neuropathic pain.

Assessment of local tissue water in the arms and trunk of breast cancer survivors with and without upper extremity lymphoedema.

Given the paucity of information on local tissue water (LTW) in the upper extremity and trunk of women after breast cancer surgery, the purpose of this study was to compare tissue dielectric constant (TDC) values between the affected and unaffected sides of breast cancer survivors with and without upper extremity lymphoedema (LE). Differences in LTW were assessed using the TDC method for three sites in the upper limbs, three sites in the lateral thorax and two sites on the back. Additional measures included demographic and clinical characteristics, arm circumference and bioimpedance analysis. For the 112 survivors without LE, no differences in TDC values were found between the affected and unaffected sides for the first dorsal web space, ventral forearm and upper arm, and upper and lower back. Compared to the unaffected side, TDC values were significantly higher on the affected side for the upper, mid and lower lateral thorax. For the 78 survivors with LE, compared to the unaffected side, TDC was significantly higher on the affected side for all of the sites evaluated except the hand web space. Our findings support the use of the TDC method to detect differences in upper extremity and truncal oedema in survivors with LE following breast cancer treatment. Measurement of LTW may provide a useful method to determine truncal as well as extremity LE. The ability to detect early signs of truncal oedema may lead to pre-emptive interventions in breast cancer survivors.

Expression of mitochondrial dysfunction-related genes and pathways in paclitaxel-induced peripheral neuropathy in breast cancer survivors.

BACKGROUND: Paclitaxel is one of the most commonly used drugs to treat breast cancer. Its major dose-limiting toxicity is paclitaxel-induced peripheral neuropathy (PIPN). PIPN persists into survivorship and has a negative impact on patient's mood, functional status, and quality of life. No interventions are available to treat PIPN. A critical barrier to the development of efficacious interventions is the lack of understanding of the mechanisms that underlie PIPN. Mitochondrial dysfunction has been evaluated in preclinical studies as a hypothesized mechanism for PIPN, but clinical data to support this hypothesis are limited. The purpose of this pilot study was to evaluate for differential gene expression and perturbed pathways between breast cancer survivors with and without PIPN. METHODS: Gene expression in peripheral blood was assayed using RNA-seq. Differentially expressed genes (DEG) and pathways associated with mitochondrial dysfunction were identified between survivors who received paclitaxel and did (n = 25) and did not (n = 25) develop PIPN. RESULTS: Breast cancer survivors with PIPN were significantly older; more likely to be unemployed; reported lower alcohol use; had a higher body mass index and poorer functional status; and had a higher number of lower extremity sites with loss of light touch, cold, and pain sensations and higher vibration thresholds. No between-group differences were found in the cumulative dose of paclitaxel received or in the percentage of patients who had a dose reduction or delay due to PIPN. Five DEGs and nine perturbed pathways were associated with mitochondrial dysfunction related to oxidative stress, iron homeostasis, mitochondrial fission, apoptosis, and autophagy. CONCLUSIONS: This study is the first to provide molecular evidence that a number of mitochondrial dysfunction mechanisms identified in preclinical models of various types of neuropathic pain including chemotherapy-induced peripheral neuropathy are found in breast cancer survivors with persistent PIPN and suggest genes for validation and as potential therapeutic targets.

Phenotypic Characterization of Paclitaxel-Induced Peripheral Neuropathy in Cancer Survivors.

CONTEXT: Although paclitaxel is one of the most commonly used drugs to treat breast, ovarian, and lung cancers, little is known about the impact of paclitaxel-induced peripheral neuropathy (PIPN) on cancer survivors. OBJECTIVES: The purposes of this study were to evaluate for differences in demographic and clinical characteristics as well as measures of sensation, balance, upper extremity function, perceived stress, symptom burden, and quality of life (QOL) between survivors who received paclitaxel and did (n = 153) and did not (n = 58) develop PIPN. METHODS: Pain characteristics associated with PIPN are described in detail. Both subjective and objective measures were used to evaluate the impact of PIPN. RESULTS: Survivors with PIPN were significantly older, had a higher body mass index, and a worse comorbidity profile. The duration of PIPN was almost four years, and pain scores were in the moderate range. Compared with survivors without PIPN, survivors with PIPN had a higher number of upper and lower extremity sites that had lost light touch, cold, and pain sensations. Survivors with PIPN had worse upper extremity function, more problems with balance, a higher symptom burden, and higher levels of perceived stress. In addition, survivors with PIPN had worse QOL scores particularly in the domain of physical functioning. CONCLUSION: The findings from this large descriptive study are the first to document the impact of PIPN on survivors' symptom burden, functional status, and QOL.

RELIABILITY AND VALIDITY OF THE HALO DIGITAL GONIOMETER FOR SHOULDER RANGE OF MOTION IN HEALTHY SUBJECTS.

BACKGROUND: Range of motion (ROM) of the shoulder is an integral component of assessment of musculoskeletal shoulder impairments. ROM is typically measured using a universal goniometer (UG). The UG has demonstrated good intra and inter-rater reliability for measuring shoulder ROM, although limitations exist. In recent years, alternative measurement devices such as smartphone applications and digital goniometers have been introduced, potentially addressing some of the shortcomings of the UG. Limited research is available on the validity and reliability of these alternative devices, including the laser-guided digital goniometer, in measuring shoulder ROM.Purpose: The purpose of this study was to investigate the intra- and inter-rater reliability and concurrent validity of a laser-guided digital goniometer (HALO) for measuring active shoulder ROM. METHODS: A convenience sample of healthy volunteers was recruited. To be eligible, participants were required to be between 18 and 75 years of age and able to actively move at least one shoulder into 90 ° of glenohumeral abduction. Self-report of previous significant shoulder injury; previous shoulder surgery; current bilateral shoulder pain; current neck or upper back pain; or referred pain into the upper extremity were exclusion criteria. Active shoulder flexion, abduction, internal rotation, and external rotation were measured for each shoulder. Two evaluators measured each motion twice with each device (HALO and the UG) per shoulder. The intra-class correlation coefficient (ICC) for reliability and validity/agreement between devices was calculated using a two-way mixed model with a 95% confidence interval. RESULTS: Data were analyzed for 75 shoulders from 41 participants (seven participants had only one shoulder evaluated). Intra-rater reliability ICCs are between 0.82 and 0.91 for the HALO, and 0.83 to 0.95 for the UG. Inter-rater reliability for the HALO was 0.89 to 0.98 and for the UG was 0.90 to 0.98. The ICCs for agreement, comparing the HALO digital goniometer to the UG ranged from 0.79 to 0.99. CONCLUSION: This study provides evidence that the HALO digital goniometer can be a reliable and valid tool for measuring shoulder ROM in individuals with healthy shoulders. However, the two devices should not be used interchangeably to evaluate a single individual's change over time for any motion. LEVEL OF EVIDENCE: Diagnostic Study (clinical measurement), Level 2b.

Lymphedema following cancer therapy: overview and options.

This summit focusing on lymphedema following cancer therapy was held during the 7th International Symposium on Cancer Metastasis through the Lymphovascular System. It was unique for the inclusion of patients with lymphedema joining physicians, therapists, healthcare professionals, and researchers to highlight what is known and more importantly what is unknown about the current state of research and treatment in the United States. The session opened with an introduction to lymphedema and then explored the incidence of multiple cancer-related lymphedemas, imaging tools and techniques useful for the diagnosis of lymphatic system abnormalities, and the new findings concerning the genetics of cancer-related lymphedema. It closed with a review of advocacy for patients and healthcare professionals and both conservative and surgical treatment options, followed by a panel discussion and questions. The session provided important information and updates which will be of value for improving the rehabilitation and overall support of patients with cancer-related lymphedema.

Associations Between Catecholaminergic and Serotonergic Genes and Persistent Breast Pain Phenotypes After Breast Cancer Surgery.

Genetic variations in the catecholaminergic and serotonergic pathways may contribute to the development and severity of persistent breast pain. However, investigations of these associations are limited. The purpose of this study was to evaluate for associations between breast pain phenotypes and single nucleotide polymorphisms among 15 genes involved in catecholaminergic and serotonergic neurotransmission. Women rated the presence and intensity of breast pain monthly for 6 months after breast cancer surgery. Distinct latent classes of patients were identified using growth mixture modeling. Logistic regression analyses identified significant differences between genotype or haplotype frequencies and the breast pain classes (ie, no breast pain [n = 96] vs mild breast pain [n = 141], moderate breast pain [n = 46], and severe breast pain [n = 27]). Polymorphisms in 5 genes were associated with membership in the mild pain class: ** beta-2-adrenergic receptor (ADRB2) rs2400707, beta adrenergic receptor kinase 2 (ADRBK2) HapA04, 5-hydroxytryptamine receptor 3A (HTR3A) rs10160548, solute-like carrier (SLC) family 6 member 2-noradrenaline transporter (SLC6A2) rs1566652, and tryptophan hydroxylase 2 (TPH2) rs11179000. Polymorphisms in 3 genes were associated with membership in the moderate pain class: 5-hydroxytryptamine receptor 2A (HTR2A) rs2296972, SLC6A2 rs17841327, and SLC6A3 rs403636. Polymorphisms in 3 genes were associated with membership in the severe pain class: COMT HPS haplotype, SLC family 6 member 2-noradrenaline transporter (SLC6A2) HapD01, and SLC family 6 member 3-noradrenaline transporter (SLC6A3) rs464049. The identification of these associations suggest possible underlying mechanisms that play a role in the development and severity of persistent breast pain. PERSPECTIVE: Findings from this study of women with breast cancer suggest that a number of catecholaminergic and serotonergic mechanisms may play a role in the development and severity of persistent breast pain phenotypes after surgery.

Associations Between Perceived Stress and Chemotherapy-Induced Peripheral Neuropathy and Otoxicity in Adult Cancer Survivors.

CONTEXT: The most common adverse effects from neurotoxic chemotherapy are chemotherapy-induced neuropathy (CIPN), hearing loss, and tinnitus. Although associations between perceived stress and persistent pain, hearing loss, and tinnitus are documented, no studies have examined these associations in cancer survivors who received neurotoxic chemotherapy. OBJECTIVES: In this cross-sectional study, we evaluated for associations between perceived stress and the occurrence of CIPN, hearing loss, and tinnitus, in 623 adult cancer survivors who received platinum and/or taxane compounds. METHODS: Survivors completed self-report measures of hearing loss, tinnitus, and perceived stress (i.e., Impact of Events Scale-Revised [IES-R]). Separate logistic regression analyses were done for each neurotoxicity to evaluate whether each of the IES-R subscale (i.e., intrusion, avoidance, hyperarousal) and total scores made a significant independent contribution to neurotoxicity group membership. RESULTS: Of the 623 survivors in this study, 68.4% had CIPN, 34.5% reported hearing loss, and 31.0% reported tinnitus. Older age, higher body mass index, poorer functional status, being born prematurely, cancer diagnosis, and higher intrusion (P = 0.013), hyperarousal (P = 0.014), and total (P = 0.047) IES-R scores were associated with CIPN. Older age, being male, poorer functional status, a worse comorbidity profile, and a higher IES-R hyperarousal (P = 0.007) score were associated with hearing loss. Being male, having less education, a worse comorbidity profile, and a higher IES-R hyperarousal (P = 0.029) score were associated with tinnitus. CONCLUSION: These findings suggest that increased levels of perceived stress are associated with the most common chemotherapy-induced neurotoxicities.