Age-Related Decline in Patient-Reported Outcomes 2 and 5 Years Following Total Hip Arthroplasty.

BACKGROUND: Patient-reported outcome measures (PROMs) help assess therapeutic effectiveness. This study assessed the effect of advanced age on the Hip Disability and Osteoarthritis Outcome Score (HOOS) and Lower Extremity Activity Scale (LEAS) after total hip arthroplasty (THA). METHODS: A prospective cohort of patients underwent primary THA at our institution between May 2007 and December 2011. Exposure was age at the time of surgery and outcomes were HOOS and LEAS scores 2 and 5 years postsurgery. We used a multivariable longitudinal generalized estimating equation to elucidate the effect of age on PROM scores. RESULTS: Our analysis of 3700 THA patients (mean age, 66 years; 56.4% female) demonstrated a decline in scores by age for the LEAS, HOOS Activities of Daily Living, and HOOS Sport and Recreation domains. There was also association between age and HOOS Symptoms and HOOS Quality of Life domains, but not between age and the HOOS Pain domain. Critical ages at which the relationship between age and outcome changed was 63 years for the HOOS Pain, Symptom, Activities of Daily Living, and Quality of Life domains, and 72 years for the HOOS Sport and Recreation domain and the LEAS. CONCLUSION: Patients undergoing THA at older ages reported lower activity and sports and recreation scores than younger patients, but similar pain, symptoms, and quality of life scores. This knowledge can help physicians guide patients' expectations before THA. Our findings also indicate that PROM scores should be age adjusted when used for quality or value comparisons between hospitals or physicians.

Age-Related Functional Decline Following Total Knee Arthroplasty: Risk Adjustment is Mandatory.

BACKGROUND: Patient-reported outcome measures (PROMs) are being used increasingly to determine the success of total knee arthroplasty (TKA). Our goal is to investigate whether advanced age is associated with lower PROM scores. METHODS: We used our hospital's TKA registry to examine the relationship between age and PROMs in all patients 50-90 years of age who underwent unilateral or simultaneous bilateral primary TKA between 2007 and 2011 with a primary diagnosis of osteoarthritis. All 5 domains of the Knee Injury and Arthritis Outcomes Score (KOOS) and the Lower Extremity Activity Scale (LEAS) at baseline, 2 years, and 5 years were collected. The association between age and PROM score was assessed by piecewise linear regression using generalized estimating equations, adjusting for demographics, comorbidity, and baseline score. RESULTS: Significant nonlinear relationships among age, KOOS subdomains, and LEAS were found. The placement of the age spline knot was at 70 years for KOOS Symptom and 68 years for KOOS Pain, KOOS Activities of Daily Living (ADL), and LEAS. The KOOS Symptom domain showed a significant worsening between 2-year and 5-year follow-up (P < .05) as patients got older. CONCLUSION: We found an age-related decline in KOOS Pain, KOOS Symptom, KOOS ADL, and LEAS scores. The best fitting spline knots were at 68 (KOOS Pain, KOOS ADL, and LEAS) and 70 years (KOOS Symptoms), respectively. This demonstrates that there is a critical age at which functional decline begins regardless of the quality of the TKA surgery. Our findings will help surgeons accurately guide patient expectations after TKA based on age. LEVEL OF EVIDENCE: Level II, prognostic study.

Romidepsin (FK228) combined with cisplatin stimulates DNA damage-induced cell death in ovarian cancer.

OBJECTIVE: Romidepsin (FK228) was recently approved by the FDA for the treatment of cutaneous and peripheral T cell lymphoma. We have shown in vitro efficacy of FK228 in ovarian cancer. Here, our goal was to evaluate FK228 combined with cisplatin in ovarian cancer in vitro and in vivo. METHODS: Ovarian cancer cell lines were treated with cisplatin, FK228 or the combination of drugs. Colorimetric assays were used to determine cytotoxicity in vitro. Mice engrafted with 5×10(6) SKOV-3 ovarian cancer cells were treated with cisplatin, FK228 or the combination, and tumor weights and volumes were measured. We assessed molecular markers of proliferation (mib-1), apoptosis (cleaved PARP and cleaved caspase 3) and DNA damage (pH2AX, RAD51 and 53BP1). RESULTS: FK228 enhanced the cytotoxic effects of cisplatin in ovarian cells compared to vehicle-treated controls or each drug alone. The combination of FK228 and cisplatin-induced apoptosis and activated aberrant DNA damage responses demonstrated by increased expression of pH2AX, RAD51 and 53BP1. Mice treated with FK228, cisplatin and both drugs showed reduced tumor weights and volumes. Drug-treated tumors showed decreased mib-1 and increased cleaved-caspase 3 expression levels. The number and intensity of pH2AX stained cells was greatest in tumors exposed to the combination of FK228 and cisplatin. CONCLUSION: FK228 causes DNA damage-induced apoptosis and enhances the anti-tumor effects of cisplatin. The DNA damage mark pH2AX is activated by FK228 and cisplatin and may be a useful pharmacodynamic mark of these effects.