Citations

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.

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.

AbstractObjectivesThis study reports long‐term outcomes percutaneous Melody valve (Medtronic, Minneapolis, Minnesota) valve‐in‐valve therapy in patients with prosthetic valve dysfunction.BackgroundRepeat valve surgery is associated with high morbidity and mortality. Transcatheter mitral valve‐in‐valve is a promising alternative in patients at high‐risk for cardiac surgery.MethodsWe conducted a retrospective cohort analysis of 13 patients who underwent Melody valve‐in‐valve for bioprosthetic dysfunction from July 2011 to October 2013.ResultsMean age was 74.4 years, 46% male, and STS score 13.5 ± 6.8%. All patients had NYHA class 3 or 4 symptoms with improvement to class 1 or 2 in 82% post procedure. Median follow‐up was 4.5 years with longest follow‐up of 5.5 years. Thirty‐day mortality was 15.4% with 1‐year mortality of 25% and no other reported deaths until 4.5 years. 76.9% of patients had mitral gradient of 5 mmHg or less immediately postprocedure. One patient required repeat valve procedure for structural deterioration at 4.4 years. At 1, 3, and 5 year follow‐ups 75% of patients were NYHA class 1 or 2, mean gradients were 4.5 ± 0.6, 6.8 ± 0.5, and 7.5 ± 0.7, respectively. Using 4‐point scale, mitral regurgitation postprocedure was 0.8 ± 0.6. At 1, 3, and 5 years this increased to 1.0 ± 1.1, 1.3 ± 1.3, and 2.5 ± 2.1, respectively.ConclusionsMelody valve‐in‐valve therapy was effective with 1‐year symptomatic improvement. Prosthesis deterioration requiring repeat intervention was observed in one patient. Larger cohorts with multicenter registries are needed to determine the role of this percutaneous valve‐in‐valve therapy as valve technology and procedural techniques improve.

AbstractWe present a case of a 7‐year‐old boy with a history of multiple mitral valve interventions and subsequent Melody valve placement in the mitral position, who presented with acute mitral stenosis due to complete fracture of the Melody stent. He was born early with severe mitral and tricuspid insufficiency due to valvular dysplasia, and ended up with 4 sternotomies before the age of 2 due to mitral valve dysfunction and recurrent prosthetic valve thrombosis. He then developed mixed stenosis and regurgitation at age 6, and to avoid another sternotomy, valve‐in‐valve therapy with off‐label use of a 20‐mm Melody valve was done with hybrid procedure via trans‐apical approach. Eight months later he presented with acutely worsened mitral stenosis (mean gradient 20 mm Hg), due to fracture of the proximal stent. While the safety and efficacy of the Melody valve has been well established especially in the pulmonary position, stent fracture is a known and potentially serious complication. As with any novel valve therapy, close follow‐up and frequent imaging may be warranted to watch for loss of stent integrity, particularly if clinical symptoms of valve dysfunction occur.

BACKGROUND: There are few comparative data on the analgesic options used to manage patients undergoing minimally invasive repair of pectus excavatum (MIRPE). The Society for Pediatric Anesthesia Improvement Network was established to investigate outcomes for procedures where there is significant management variability. For our first study, we established a multicenter observational database to characterize the analgesic strategies used to manage pediatric patients undergoing MIRPE. Outcome data from the participating centers were used to assess the association between analgesic strategy and pain outcomes. METHODS: Fourteen institutions enrolled patients from June 2014 through August 2015. Network members agreed to an observational methodology where each institution managed patients based on their institutional standards and protocols. There was no requirement to standardize care. Patients were categorized based on analgesic strategy: epidural catheter (EC), paravertebral catheter (PVC), wound catheter (WC), no regional (NR) analgesia, and intrathecal morphine techniques. Primary outcomes, pain score and opioid consumption by postoperative day (POD), for each technique were compared while adjusting for confounders using multivariable modeling that included 5 covariates: age, sex, number of bars, Haller index, and use of preoperative pain medication. Pain scores were analyzed using repeated-measures analysis of variance with Bonferroni correction. Opioid consumption was analyzed using a multivariable quantile regression. RESULTS: Data were collected on 348 patients and categorized based on primary analgesic strategy: EC (122), PVC (57), WC (41), NR (120), and intrathecal morphine (8). Compared to EC, daily median pain scores were higher in patients managed with PVC (POD 0), WC (POD 0, 1, 2, 3), and NR (POD 0, 1, 2), respectively ( P < .001–.024 depending on group). Daily opioid requirements were higher in patients managed with PVC (POD 0, 1), WC (POD 0, 1, 2), and NR (POD 0, 1, 2) when compared to patients managed with EC ( P < .001). CONCLUSIONS: Our data indicate variation in pain management strategies for patients undergoing MIRPE within our network. The results indicate that most patients have mild-to-moderate pain postoperatively regardless of analgesic management. Patients managed with EC had lower pain scores and opioid consumption in the early recovery period compared to other treatment strategies.

Background. Kidney transplantation confers substantial survival and quality of life benefits for many patients with end-stage kidney disease compared with dialysis, but complications and side effects of immunosuppression can impair participation in daily life activities. Life participation is a critically important patient-reported outcome for kidney transplant recipients but is infrequently and inconsistently measured in trials. We convened a consensus workshop on establishing an outcome measure for life participation for use in all trials in kidney transplantation. Methods. Twenty-five (43%) kidney transplant recipients/caregivers and 33 (57%) health professionals from 8 countries participated in 6 facilitated breakout group discussions. Transcripts were analyzed thematically. Results. Four themes were identified. Returning to normality conveyed the patients’ goals to fulfill their roles (ie, in their family, work, and community) and reestablish a normal lifestyle after transplant. Recognizing the diverse meaning and activities of “life” explicitly acknowledged life participation as a subjective concept that could refer to different activities (eg, employment, recreation, family duties) for each individual patient. Capturing vulnerability and fluctuations posttransplant (eg, due to complications and side-effects) distinguished between experiences in the first year posttransplant and the long-term impact of transplantation. Having a scientifically rigorous, feasible, and meaningful measure was expected to enable consistent and frequent assessment of life participation in trials in kidney transplantation. Conclusions. A feasible and validated core outcome measure for life participation is needed so that this critically important patient-reported outcome can be consistently and meaningfully assessed in trials in kidney transplantation to inform decision making and care of recipients.

SummaryBackgroundChildren undergoing posterior spinal fusion experience high blood loss often necessitating transfusion. An appropriately activated coagulation system provides hemostasis during surgery, but pathologic dysregulation can cause progressive bleeding and increased transfusions. Despite receiving antifibrinolytics for clot stabilization, many patients still require transfusions.AimsWe sought to examine the association of dilutional coagulopathy with blood loss and blood transfusion in posterior spinal fusion for pediatric scoliosis patients.MethodsA retrospective, single institution study of children undergoing posterior spinal fusion >6 levels with a standardized, prospective anesthetic protocol utilizing antifibrinolytics. Blood loss was evaluated using a hematocrit‐based calculation. To evaluate transfusions, a normalized Blood Product Transfusion calculation was developed. Factors associated with blood loss and blood transfusions were determined by univariate analysis and multivariate regression modeling with multicollinearity and mediation analysis.ResultsPatients received 73.7 mL/kg (standard deviation ±30.8) of fluid poor in coagulation factors. Estimated blood loss was 42.6 mL/kg (standard deviation ±18.0). There was a significant association between estimated blood loss and total fluids delivered (Spearman's rho = 0.51, 95% confidence interval 0.33‐0.65, P < 0.001). Factors significantly associated with normalized Blood Product Transfusion in this cohort included age, weight, scoliosis type, levels fused, total osteotomies, pelvic fixation, total fluid, maximum prothrombin time, and minimum fibrinogen. Regression modeling showed the best combination of variables for modeling normalized Blood Product Transfusion included patient weight, number of levels fused, total fluid administered, and maximum prothrombin time.ConclusionBlood product transfusion remains a frustrating problem in pediatric scoliosis. Identifying and controlling dilutional coagulopathy in these patients may reduce blood loss and the need for blood transfusion.

AbstractObjectiveTo study the effect of percutaneous paravalvular leak closure on hemolysis.BackgroundAlthough transcatheter PVL closure reduces heart failure and mortality in symptomatic patients with paravalvular leaks (PVL), little is known about its effect on hemolysis.MethodsWe retrospectively analyzed patients undergoing transcatheter mitral or aortic PVL closure (January 2005–December 2016) at Mayo Clinic. Patients with anemia or abnormal hemolysis markers (LDH, haptoglobin) were included in the analysis. The primary outcome was defined as hemoglobin increase ≥ 1.5 mg/dL, decrease in LDH above median or improvement in haptoglobin. Univariate and multivariate binary logistic regression modeling were used to determine predictors of successful treatment of hemolysis.ResultsFinal study population included 168 patients (130 [77%] mitral, 38 [23%] aortic PVL). Primary outcome occurred in 70 patients (42%). Hemoglobin increased by 1.74 ± 1.69 mg/dL in patients who reached primary outcome. 57/168 (34%) patients required blood transfusion prior to PVL closure compared to 35/168 (21%) postprocedure. The mean reduction in LDH was 403 U/L. Multivariate regression showed that patients with mechanical valves were more likely to have successful outcome (P = 0.044).ConclusionPercutaneous PVL closure is associated with modest improvement in hemolysis markers, increase in hemoglobin levels and reduction in blood transfusion requirements. This benefit is most significant in patients with mechanical valves.