Citations

AbstractBackgroundPrognosis among patients with differentiated thyroid cancer is widely variable. Better understanding of biologic subtypes is necessary to stratify patients and improve outcomes.MethodsIn patients diagnosed with classic histology papillary thyroid cancer treated from 1973 to 2009, BRAF V600E mutation status was determined on surgical tumor specimens by restriction fragment length polymorphism analysis. A tissue microarray (TMA) was constructed from tumor specimens in triplicate and stained by immunohistochemistry for RET, phospho‐MEK, MAPK(dpERK), PPARγ, and phospho‐AKT(pAKT). Stained slides were scored independently and blindly by two investigators and compared to tumor and patient characteristics and outcomes.ResultsA total of 231 patients had archived formalin‐fixed, paraffin‐embedded tumor tissue available and were included on the TMA. Mean age at diagnosis was 44 years (range 6‐82 years); proportion of patients with female sex was (72%); 2015 American Thyroid Association (ATA) risk stratification was low (26%), intermediate (32%), and high (42%). BRAF V600E mutation was found in 74% of specimens, and IHC was scored as positive for RET (61%), MAPK (dpERK) (14%), PPARγ (27%), and pAKT (39%). Positive RET staining was associated with a lower risk of recurrence (HR = 0.46, 95% CI 0.22‐0.96). No other molecular biomarkers were independent predictors of recurrence on univariable analysis. On RPA, patients with RET‐negative and either MAPK(dpERK)‐positive or pAKT‐positive tumors were identified to have a high risk of recurrence (HR = 5.4, 95%CI 2.5‐11.7). This profile remained associated with recurrence in a multivariable model including ATA risk stratification (HR = 2.8, 95% CI 1.3‐6.0).ConclusionCharacterization of molecular pathways involved in cPTC tumorigenesis may add further risk stratification for recurrence beyond the 2015 ATA risk categories alone.

Abstract Background This study evaluated the association between health-related quality of life (HRQOL) and cognition in patients receiving memantine for prevention of cognitive dysfunction during whole-brain radiotherapy (WBRT). Methods Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine, 20 mg per day, within 3 days of initiating radiotherapy, for 24 weeks. The Functional Assessment of Cancer Therapy-Brain module (FACT-Br) and Medical Outcomes Scale-Cognitive Functioning Scale (MOS-C) were completed in coordination with serial standardized tests of cognitive function. Results Of the 508 eligible patients, 442 (87%) consented to participate in the HRQOL portion and contributed to baseline analyses. Evaluable patients at 24 weeks (n = 246) included surviving patients completing FACT-Br, MOS-C, and objective cognitive assessments (n = 146, 59%) and patients alive at time of missed assessment (n = 100, 41%). Baseline cognitive function correlated significantly with FACT-Br and MOS-C self-reports. All domains of objective cognitive function showed declines over time. Neither FACT-Br nor MOS-C differed between the treatment arms. Emotional and functional well-being subscales of the FACT improved over time while the remainder of the FACT-Br domains remained stable. MOS-C scores declined over time. Conclusion Baseline cognitive function correlated significantly with FACT-Br and MOS-C scores. No by-arm differences in HRQOL were observed despite differences in objective cognitive function. Patient attrition and poor testing compliance remain significant problems in studies of cognitive function of brain metastases patients and further effort is needed to improve compliance with testing and sensitivity of patient-reported measures.

202 Background: Fractional CO2 laser therapy is an emerging treatment for GSM. The objective of this study was to determine the feasibility, tolerability and preliminary efficacy of fractional CO2 laser therapy in BC survivors. Methods: This was a single arm feasibility study of BC survivors with dyspareunia and/or vaginal dryness. Participants received three treatments with office-based fractional CO2 laser on at least 30 day intervals and returned for a one-month follow-up. Feasibility was defined as treatment completion without serious adverse events (SAE) in a minimum of 80% of patients. Primary efficacy was evaluated using the mean change (∆) in the score on the Vaginal Assessment Scale (VAS). Secondary efficacy endpoints included mean ∆ in scores on the Female Sexual Function Index (FSFI) and Urogenital Distress Inventory (UDI). Descriptive statistics (means and 95% confidence intervals (CI) for continuous variables and proportions for categorical variables) were used. Results: The study is ongoing with 65 patients enrolled. To date, 37 patients have completed all study treatments and follow-up. Median age for those who have completed treatment was 57 years (range 34-72). Most were ER/PR positive (78%) and Her 2 negative (81%) with stage I (43%) or II (41%) BC. Ninety-five percent were receiving endocrine therapy, most commonly aromatase inhibitors (73%). No SAEs were reported in the 37 patients who have completed study treatments and their outcomes are as follows. Based on the VAS, 78% reported moderate-severe dyspareunia and 89% reported moderate-severe vaginal dryness at baseline. At follow up, 28% reported moderate-severe dyspareunia and 28% reported moderate-severe vaginal dryness. The VAS score improved from baseline to follow up (mean ∆ 4.1; 95% CI [3.1, 5.1]). Similarly, the FSFI score improved (mean ∆ -10.0; 95% CI [-13.2, -6.9]) and the UDI score improved (mean ∆ -5.7; 95% CI [-10.1, -1.3]). Final efficacy analysis will be reported once all patients have completed all time points. Conclusions: Fractional CO2 laser treatment is feasible and tolerable in BC survivors and may reduce symptom burden from GSM. A randomized controlled trial with sham laser is currently in development. Clinical trial information: NCT03307044.

Background: The association between quadriceps strength and functional outcomes after anterior cruciate ligament reconstruction (ACLR) is a focus of current research, while evaluations of hamstring strength are limited, despite the frequent use of hamstring autografts. Purpose/Hypothesis: The purpose of this study was to determine the relationship between changes in quadriceps and hamstring strength symmetry and self-reported outcomes before ACLR and at 12 and 24 weeks after surgery. We hypothesized that improvements in quadriceps and hamstring strength symmetry would be correlated with improvements in self-reported outcome measures within the first 6 months after ACLR. Study Design: Cohort study; Level of evidence, 2. Methods: Thirty patients who underwent ACLR with a hamstring autograft were enrolled. Quadriceps and hamstring strength and Knee injury and Osteoarthritis Outcome Score (KOOS) values were assessed before and at 12 and 24 weeks after ACLR; limb symmetry indexes for strength were calculated at each time point. The Friedman and Wilcoxon signed-rank tests were used to analyze changes in KOOS values over time. Spearman rank-order correlations were used to test the relationship between changes in strength and KOOS values between each time point. Results: Hamstring and quadriceps limb symmetry significantly increased with time ( P ≤ .03). Fair correlations were observed between changes in the hamstring index and changes in the KOOS Symptoms subscore from before surgery to 12 weeks postoperatively ( r = 0.48; P ≤ .05). Changes in the quadriceps index (QI) were moderately correlated with changes in the KOOS Sport/Recreation subscore ( r = 0.60; P = .001), and fair correlations were seen between the QI and the KOOS Quality of Life subscore ( r = 0.39; P ≤ .04) from preoperatively to 12 weeks after surgery. Moderate correlations were seen between the QI and the KOOS Sport/Recreation subscore ( r = 0.57; P = .005) from 12 to 24 weeks after surgery. Conclusion: Improvements in quadriceps and hamstring strength symmetry were modestly associated with improvements in athletes’ perceived function in the first 6 months after ACLR. Specifically, improvements in hamstring symmetry were associated with improvements in knee symptoms within the first 12 weeks postoperatively, while improvements in quadriceps symmetry were associated with improvements in self-reported sport function throughout the first 6 months after ACLR. The restoration of strength symmetry within the first 6 months may be a critical component of rehabilitation aimed at maximizing function after ACLR. Further investigation is warranted to comprehensively evaluate whether the timing of strength gains predicts future function, including those who successfully return to their preinjury activity level after ACLR.

ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell‐released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV‐associated functional activities. Finally, a checklist is provided with summaries of key points.

Abstract Although a woman's healthcare provider has the best opportunity to address hypoactive sexual desire disorder (HSDD), most women are reluctant to discuss their loss of sexual desire. The feeling is often mutual, because limited education and misunderstanding persist, leaving few providers feeling competent to assess and treat this condition. The purpose of this Practice Pearl is to improve the clinician's understanding of and confidence in discussing HSDD, including symptoms, etiology, burden, diagnosis, and treatment.

ObjectivesTo evaluate the ability of claims‐based risk adjustment and incremental components of clinical data to identify 90‐day episode costs among lower extremity joint replacement (LEJR) patients according to the Centers for Medicare & Medicaid Services (CMS) Comprehensive Care for Joint Replacement (CJR) program provisions.Data SourcesMedicare fee‐for‐service (FFS) data for qualifying CJR episodes in the United States, and FFS data linked with clinical data from CJR‐qualifying LEJR episodes performed at High Value Healthcare Collaborative (HVHC) and Mayo Clinic in 2013. HVHC and Mayo Clinic populations are subsets of the total FFS population to assess the additive value of additional pieces of clinical data in correctly assigning patients to cost groups.Study DesignMultivariable logistic models identified high‐cost episodes.Data Collection/Extraction MethodsClinical data from participating health care systems merged with Medicare FFS data.Principal FindingsOur three populations consisted of 363 621 patients in the CMS population, 4881 in the HVHC population, and 918 in the Mayo population. When modeling per CJR specifications, we observed low to moderate model performance (CMS C‐Stat = 0.714; HVHC C‐Stat = 0.628; Mayo C‐Stat = 0.587). Adding CMS‐HCC categories improved identification of patients in the top 20% of episode costs (CMS C‐Stat = 0.758, HVHC C‐Stat = 0.692, Mayo C‐Stat = 0.677). Clinical variables, particularly functional status in the population for which this was available (Mayo C‐Stat = 0.783), improved ability to identify patients within cost groups.ConclusionsPolicy makers could use these findings to improve payment adjustments for bundled LEJR procedures and in consideration of new data elements for reimbursement.