Cardiotoxicity of breast cancer chemotherapy.

Breast cancer is one of the leading causes of malignancy affecting women in the United States. Although many effective treatments are available, most come with notable side effects that providers and patients must take into consideration. Various classes of chemotherapeutic agents, including anthracyclines and human epidermal growth factor receptor-2 antagonists, are known to be toxic to myocardial tissue. In this review article, we discuss what is reported in the literature regarding the cardiotoxicity of these agents as well as how to monitor and prevent cardiac injury and dysfunction.

The predictive value of self-reported allergies for reoperation after index hip arthroscopy.

The purpose of this study is to compare the rate of reoperation after index hip arthroscopy for symptomatic femoroacetabular impingement in patients with, and without, at least one self-reported allergy. Data were collected prospectively in 1468 patients whose records were retrospectively reviewed. After the application of inclusion and exclusion criteria, two cohorts were formed: (i) a study cohort (n = 261) composed of patients with a self-reported allergy and (ii) a control cohort. (n = 666). The allergy cohort had a significantly larger [P < 0.001] reoperation rate (24.1% [63/261]) compared to the control cohort (9.6% [64/66]). Univariate analysis (UVA) and multivariate analysis (MVA) were then performed to better understand the implications of allergy status on the arthroscopic outcome. On UVA the presence of an allergy increased the odds of reoperation after index hip arthroscopy by 2.99 [OR (95% CI): 2.99 (2.04, 4.39); P < 0.001] and for each additional allergy a patient reported, their odds of subsequent surgery increased by 1.27 per allergy [OR (95% CI): 1.27 (1.15, 1.39); P < 0.001]. However, on the MVA, allergy status was not an independent risk factor for reoperation. These findings suggest that allergy status is associated with a higher reoperation rate, however, allergy status alone cannot prognosticate the risk of subsequent surgery. Therefore, allergy status and its association with future surgery after hip arthroscopy should be considered in the context of multiple patient-specific factors that influence the surgical outcome. An understanding of this association enables patient-centered care and will strengthen the physician-patient relationship.

Failure to Achieve Threshold Scores on Patient-Reported Outcome Measures Within 1 Year Has a Predictive Risk of Subsequent Hip Surgery Within 5 Years of Primary Hip Arthroscopy: A Case-Control Study.

BACKGROUND: Research has identified factors that influence achievement rates of threshold scores on patient-reported outcome measures (PROMs) after hip arthroscopy. However, little data exist on whether failure to achieve a threshold score (minimal clinically important difference [MCID] or substantial clinical benefit [SCB]) in the short term after hip arthroscopy predicts the risk of future hip surgery. PURPOSE/HYPOTHESIS: The purpose of this study was to determine if failure to achieve the MCID or SCB on PROMs within 1 year of hip arthroscopy can be considered a risk factor for repeat surgery within 5 years of primary hip arthroscopy. It was hypothesized that failure to achieve threshold scores would increase the risk of subsequent hip surgery. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A retrospective review of prospectively collected data was completed. Four PROMs were collected preoperatively and within 1 year of hip arthroscopy: modified Harris Hip Score, Hip Outcome Score-Activities of Daily Living, Hip Outcome Score-Sports, and the 33-Item International Hip Outcome Tool. RESULTS: Two cohorts were formed: (1) a study cohort (n = 88) composed of patients who underwent repeat hip surgery within 5 years of hip arthroscopy and (2) a control cohort (n = 288) composed of patients who did not require repeat hip surgery. The study cohort had significantly (P < .001) lower scores on all postoperative PROMs, and a significantly (P < .001) smaller percentage of the study cohort met the MCID and SCB. Multivariable regression analysis demonstrated that not achieving the MCID or SCB on each of the PROMs is an independent risk factor for repeat hip surgery. For every PROM in which a patient failed to achieve the MCID, the odds of subsequent surgery increased by 1.68 (95% CI, 1.42-1.98; P < .001). For every PROM in which a patient failed to achieve the SCB, the odds of subsequent surgery increased by 1.63 (95% CI, 1.35-1.97; P < .001). CONCLUSION: Failure to meet threshold scores on PROMs after hip arthroscopy was an independent risk factor for subsequent hip surgery. This study establishes a novel utility of PROMs and confirms the importance of these metrics in the orthopaedic literature.

Weight loss does not decrease risk of breast cancer-related arm lymphedema.

BACKGROUND: The goal of this study was to determine the relationship between postoperative weight change and breast cancer-related lymphedema (BCRL). METHODS: In this cohort study, 1161 women underwent unilateral breast surgery for breast cancer from 2005 to 2020 and were prospectively screened for BCRL. Arm volume measurements were obtained via an optoelectronic perometer preoperatively, postoperatively, and in the follow-up setting every 6 to 12 months. Mean follow-up from preoperative baseline was 49.1 months. The main outcome was BCRL, defined as a relative volume change of the ipsilateral arm of ≥10% at least 3 months after surgery. RESULTS: A total of 92 patients (7.9%) developed BCRL. Net weight loss versus net weight gain from baseline to last follow-up was not protective against developing BCRL (hazard ratio, 1.38; 95% confidence interval, 0.89-2.13; P = .152). CONCLUSIONS: Although weight loss may be recommended as part of an individualized lifestyle management program for overall health, weight loss alone may not decrease the risk of developing BCRL.

Subclinical Lymphedema After Treatment for Breast Cancer: Risk of Progression and Considerations for Early Intervention.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a devastating complication of breast cancer (BC) treatment. The authors hypothesized that identifying subclinical lymphedema (SCL) presents an opportunity to prevent BCRL development. They aimed to assess rates of SCL progression (relative volume change [RVC], 5-10%) to BCRL (RVC, ≥10%) in women undergoing axillary surgery for BC via axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB). METHODS: Patients treated for BC were prospectively screened at preoperative baseline and throughout the follow-up period using the perometer. The cohort was stratified according to nodal surgery (ALND or SLNB) to analyze rates of progression to BCRL. RESULTS: The study cohort included 1790 patients. Of the 1359 patients who underwent SLNB, 331 (24.4%) experienced SCL, with 38 (11.5%) of these patients progressing to BCRL. Of the 431 patients who underwent ALND, 171 (39.7%) experienced SCL, with 67 (39.2%) of these patients progressing to BCRL. Relative to the patients without SCL, those more likely to experience BCRL were the ALND patients with early SCL (< 3 months postoperatively; hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.58-4.27; p = 0.0002) or late SCL (≥3 months postoperatively; HR, 3.14; 95% CI, 1.95-5.05; p < 0.0001) and the SLNB patients with early SCL (HR, 6.75; 95% CI, 3.8-11.98; p < 0.0001 or late SCL (HR, 3.02; 95% CI, 1.65-5.50; p = 0.0003). CONCLUSION: The study suggests that patients with SCL after axillary nodal surgery for BC are more likely to progress to BCRL than those who do not experience SCL. This presents a tremendous opportunity for early intervention to prevent BCRL and improve the quality of life for women treated for BC.

Integrating Symptoms Into the Diagnostic Criteria for Breast Cancer-Related Lymphedema: Applying Results From a Prospective Surveillance Program.

OBJECTIVE: The objectives of this study were to determine whether patients reporting symptoms are more likely to develop lymphedema and to describe the temporal relationship between symptom onset and lymphedema. METHODS: This was a prospective longitudinal cohort study of 647 women treated for breast cancer and screened for lymphedema using arm volume measurements and subjective questionnaires (n = 647; 2284 questionnaires [median 3.5 per patient, range = 1-24]). Primary study outcome was lymphedema (relative volume change ≥10%). The Kaplan-Meier method was used to estimate cumulative lymphedema incidence. Cox proportional hazards models were used to assess the relationship between symptoms, other risk factors, and lymphedema. RESULTS: A total of 64 patients (9.9%) developed lymphedema. On multivariable analysis, patients reporting increased arm size (hazard ratio = 3.09, 95% CI = 1.62-5.89) were more likely to progress to lymphedema than those who did not report this symptom. Of those who developed lymphedema, 37 (58%) reported an increased arm size a median of 6.1 months before lymphedema onset (range = 68.6 months before to 50.2 months after lymphedema onset). CONCLUSION: Patients at risk of lymphedema who report increased arm size might do so prior to lymphedema onset and are at 3 times the risk of lymphedema as patients not reporting this symptom. Even without objective or observable edema, these patients should be followed vigilantly and considered for early intervention. Symptoms should be incorporated into screening and diagnostic criteria for lymphedema. IMPACT: This study shows that patients at risk for breast cancer-related lymphedema who report increased arm size should be considered at high risk for progression to lymphedema-even without edema on measurement or clinical examination-and should be followed vigilantly, with consideration of early intervention. LAY SUMMARY: If you are at risk of lymphedema and you feel as though your arm size has increased, you might develop lymphedema, and you are at 3 times the risk of lymphedema as patients not reporting this symptom. Even without measurable or observable edema, you should be followed vigilantly and consider early intervention.

Patients who report cording after breast cancer surgery are at higher risk of lymphedema: Results from a large prospective screening cohort.

OBJECTIVES: To identify the association between cording and breast cancer-related lymphedema (BCRL); describe time course, location, symptoms and functional impairments. METHODS: A total of 1181 patients were prospectively screened for BCRL after breast cancer (BC) surgery, including patient-reported outcome measures (4193) and perometric arm volume measurements (BCRL defined as relative or weight-adjusted volume change [RVC or WAC] ≥10% ≥3 months postoperatively). RESULTS: A total of 374/1181 patients (31.7%) reported cording first a median of 4.5 months postoperatively, and were more likely to: have body mass index less than 30 kg/m2 ; be less than 55 years of age; have had mastectomy, axillary lymph node dissection, regional lymph node radiation, neoadjuvant chemotherapy (all P < .001), or RVC/WAC ≥10% (P = .002). Patients who reported cording had 2.4 times the odds of developing BCRL compared to those who did not (odds ratio = 2.40; 95% confidence interval = 1.40-4.11; P = .002), and most frequently reported these symptoms: tenderness (61.2%), aching (60.7%), and firmness/tightness (59.8%). On multivariable analysis, cording was significantly correlated with functional difficulty for 17 actions. CONCLUSIONS: Patients frequently present with cording, potentially months after BC surgery. Risk factors for and symptoms of cording are identified, and treatment is recommended. Patients reporting cording are at higher risk of BCRL, therefore, cording should be incorporated into BCRL risk stratification.

Self-reported allergies correlate with a worse patient-reported outcome after hip arthroscopy: a matched control study.

Patient-reported outcome measures (PROMs) in patients with and without at least one self-reported allergy undergoing hip arthroscopy were compared. Data on 1434 cases were retrospectively reviewed, and 267 patients were identified with at least one self-reported allergy and randomly matched to a control group on a 1:2 ratio. Four PROMs [Modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL), Hip Outcome Score-Sports (HOS-Sport) and 33-item International Hip Outcome Tool (iHOT-33)] were collected preoperatively, and at 5-11, 12-23 and 24-35 months postoperatively. Significant PROM differences were found 5-11 months postoperative on mHHS (P < 0.001), HOS-ADL (P = 0.002), HOS-Sport (P < 0.001) and iHOT-33 (P < 0.001). At 12-23 months postoperative, the allergy cohort had significantly worse scores on mHHS (P = 0.002), HOS-ADL (P = 0.001), HOS-Sport (P < 0.001) and iHOT-33 (P < 0.001). They also had significantly worse measures 24-35 months postoperative on mHHS (P = 0.019), HOS-Sport (P = 0.006) and iHOT-33 (P < 0.001). Multivariable logistic regression showed that each additional allergy reported significantly increased the risk of failing to meet the minimal clinically important difference 5-11 months after surgery on mHHS by 1.15 [OR (95% CI): 1.15 (1.03, 1.30), P = 0.014], on HOS-ADL by 1.16 [OR (95% CI): 1.16 (1.02, 1.31), P = 0.021] and on iHOT-33 by 1.20 [OR (95% CI): 1.20 (1.07, 1.36), P = 0.002]. Results suggest self-reported allergies increase the likelihood of a patient-perceived worse outcome after hip arthroscopy. An understanding of this association by the physician is essential during presurgical planning and in the management of postoperative care.

Incidence of peripheral edema in patients receiving PI3K/mTOR/CDK4/6 inhibitors for metastatic breast cancer.

PURPOSE: This study evaluated development of edema in patients receiving PI3K/mTOR/CDK4/6 targeted therapy for metastatic breast cancer (MBC). METHODS: We reviewed medical records of 160 patients receiving targeted therapy with PI3K/mTOR/CDK4/6 inhibitors to treat MBC (n = 160; 185 treatment occurrences). Clinicopathologic data, treatment details, and edema incidence were recorded. RESULTS: Edema incidence was 43.1% (69/160) overall and 25.6% (41/160) in the upper extremity ipsilateral to the treated breast. In 185 therapy regimens administered, 6.8% of patients on a PI3K inhibitor, 8.8% of patients on an mTOR inhibitor, and 9.2% of patients on a CDK4/6 inhibitor experienced new onset or worsened preexisting upper extremity edema. Further, 9.1% of patients on a PI3K inhibitor, 18.8% of patients on an mTOR inhibitor, and 10.5% of patients on a CDK4/6 inhibitor experienced new onset or worsened preexisting edema elsewhere in the body. Multivariate logistic regression showed that, beyond the established breast cancer-related lymphedema (BCRL) risk factors [axillary lymph node dissection (Odds Ratio (OR) 2.69, p = 0.020), regional lymph node irradiation (OR 6.47, p < 0.001), and body-mass index ≥ 30 kg/m2 (OR 3.46, p = 0.006)], a relative decrease in serum albumin after 3 months of treatment increased risk of developing edema (OR 2.07, p = 0.062). Neither duration nor type of therapy were significant risk factors for edema. CONCLUSION: PI3K/mTOR/CDK4/6 inhibitors may influence the development of edema, which may cause or exacerbate progression of BCRL in patients with MBC. The varied incidence of edema between therapeutic regimens warrants vigilant monitoring of patients treated with these therapies, especially those at high risk of developing BCRL.

Aplip1, the Drosophila homolog of JIP1, regulates myonuclear positioning and muscle stability.

During muscle development, myonuclei undergo a complex set of movements that result in evenly spaced nuclei throughout the muscle cell. In Drosophila, two separate pools of Kinesin and Dynein work in synchrony to drive this process. However, how these two pools are specified is not known. Here, we investigate the role of Aplip1 (the Drosophila homolog of JIP1, JIP1 is also known as MAPK8IP1), a known regulator of both Kinesin and Dynein, in myonuclear positioning. Aplip1 localizes to the myotendinous junction and has genetically separable roles in myonuclear positioning and muscle stability. In Aplip1 mutant embryos, there was an increase in the percentage of embryos that had both missing and collapsed muscles. Via a separate mechanism, we demonstrate that Aplip1 regulates both the final position of and the dynamic movements of myonuclei. Aplip1 genetically interacts with both Raps (also known as Pins) and Kinesin to position myonuclei. Furthermore, Dynein and Kinesin localization are disrupted in Aplip1 mutants suggesting that Aplip1-dependent nuclear positioning requires Dynein and Kinesin. Taken together, these data are consistent with Aplip1 having a function in the regulation of Dynein- and Kinesin-mediated pulling of nuclei from the muscle end.This article has an associated First Person interview with the first author of the paper.