Citations

Background: Meniscal repair is desirable over resection to prevent post-meniscectomy arthritis, especially in young and active patients. However, long-term data is currently lacking following meniscus repair, particularly in the pediatric population. Purpose: To report long-term follow-up of isolated meniscus tears treated by meniscal repair in a pediatric population, and to compare those results to previous mid-term follow-up data reported. We hypothesized that these patients would have satisfactory function and reoperation rates at long-term follow-up. Methods: Patients less than 18 that had a meniscal repair procedure performed between 1990 and 2005 were included. Concomitant ACL reconstructions were excluded from the present study. At the time of final follow-up, recurrent meniscus tear, reoperation rates, and IKDC and Tegner scores were determined. Wilcoxin signed ranks tests were performed to calculate the differences in clinical outcome for the 3 time points (pre-operative, average 7 years post-op, and average 18 years post-op) and Spearman coefficients were calculated for Tegner and IKDC with different variables. Results: At an average follow-up of 18 years (range 13.2 - 25.9 years), 34 patients with 35 isolated meniscus repairs (4F: 30 M) with an average age of 16 (9.9 - 18.7) were included in this study. Of the 35 knees (34 patients), none had “failed” or re-injured their affected meniscus since mid-term follow-up in 2008. The average IKDC score was 92.1 which was found to be significantly increased when compared to both preoperative IKDC 64.7 (P<.0001) and mid-term IKDC scores, 89.8 (p=.02). However, the average Tegner score (6.5) was significantly lower than both pre-operative 8.28 (p<.0001) and the mid-term Tegner average 8.25 (p<.0001). Patients with a meniscus re-tear and subsequent partial meniscectomy had lower IKDC scores than clinically successful repairs (88.9 vs 94.0), but this did not reach statistical significance (p=.09). There was no correlation for Tegner or IKDC values with 1) rim width, 2) current age, 3) time elapsed since surgery, or 4) time from injury to surgery. There were also no differences in Tegner or IKDC scores when comparing; medial versus lateral, left versus right, tear types, surgical repair technique, or male vs female. Conclusion: This study demonstrates very good clinical long-term outcomes following meniscal repair in a pediatric population.

Abstract Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P &lt; 2.2 × 10−6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10−7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P &lt; 1.47 × 10−3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis. Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419–30. ©2018 AACR.

The study comprised 170 consecutive patients (pts) seen at Mayo Clinic between 1962 and 1970 who underwent mitral valve replacement with Starr-Edwards prosthesis (model 6000 in 35% of pts, model 6120 in 65% of pts) because of significant chronic mitral incompetence (functional Class III-IV). All patients were on oral anticoagulants and were followed until January 1980 with a followup of 10 to 19 years (yrs) (median 15 yrs). We analyzed (1) the cumulative incidence of systemic emboli, their location and whether or not they left residual deficit; and (2) possible risk factors that might have been predictive, including in the analysis: age, sex, functional class, presence or absence of atrial fibrillation, degree of cardiomegaly, type of prosthesis and degree of anticoagulation.At 12 yrs of followup, 48% of pts had at least one episode of emboli (among these pts, 12% had two episodes); the rate of emboli was maximal within 1 yr postoperatively but persisted over the total followup at a rate of about 3% per yr. Of all emboli, 94% occurred in the cerebral circulation and 66% left neurological deficit. Regarding predictive factors, the incidence of emboli was slightly higher in pts with the prosthesis model 6000 (p<0.05) and in pts considered to be poorly anticoagulated (p<0.05).This unique long-term followup study on pts with mitral Starr-Edwards prosthesis reveals that systemic emboli is a persistent and significant problem. Preliminary data indicates that the addition of a platelet inhibitor to the oral anticoagulant may be beneficial.

Background. We sought to study the association between RPS case volume and outcomes. Although a relationship has been demonstrated between case volume and patient outcomes in some cancers, such a relationship has not been established for retroperitoneal sarcomas (RPSs). Study Design. The National Cancer Database (NCDB) was queried for patients undergoing treatment for primary RPS diagnosed between 2004 and 2013. Mean annual patient volume for RPS resection was calculated for all hospitals and divided into low volume (<5 cases/year), medium volume (5–10 cases/year), and high volume (>10 cases/year). Risk-adjusted regression analyses were performed to identify predictors of 30-day surgical mortality, R0 margin status, and overall survival (OS). Results. Our study population consisted of 5,407 patients with a median age of 61 years, of whom 47% were male and 3,803 (70%) underwent surgical resection. Absolute 30-day surgical mortality and R0 margin rate following surgery for low-, medium-, and high-volume institutions were 2.4%, 1.3%, and 0.5% (p=0.027) and 68%, 65%, and 82%, (p<0.001), respectively. Five-year overall survival rates for low, medium, and high-volume institutions were 56%, 57%, and 66%, respectively (p<0.001). Patients treated at low-volume institutions had a significantly higher risk of 30-day mortality (adjusted OR = 4.66, 95% CI 2.26–9.63) and long-term mortality (adjusted HR = 1.56, 95% CI 1.16–2.11) compared to high-volume institutions. Conclusion. We demonstrate the existence of a hospital sarcoma service line volume-oncologic outcome relationship for RPS at the national level and provide benchmark data for cancer care delivery systems and policy makers.

Background and objectives In the 3-year Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4 and 1-year Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trials, tolvaptan slowed the decline of eGFR in patients with autosomal dominant polycystic kidney disease at early and later stages of CKD, respectively. Our objective was to ascertain whether the reduction associated with the administration of tolvaptan is sustained, cumulative, and likely to delay the need for kidney replacement therapy. Design, setting, participants, & measurements One hundred and twenty-eight patients with autosomal dominant polycystic kidney disease participated in clinical trials of tolvaptan at the Mayo Clinic. All had the opportunity to enroll into open-label extension studies. Twenty participated in short-term studies or received placebo only. The remaining 108 were analyzed for safety. Ninety seven patients treated with tolvaptan for ≥1 year (mean±SD, 4.6±2.8; range, 1.1–11.2) were analyzed for efficacy using three approaches: ( 1 ) comparison of eGFR slopes and outcome (33% reduction from baseline eGFR) to controls matched by sex, age, and baseline eGFR; ( 2 ) Stability of eGFR slopes with duration of follow-up; and ( 3 ) comparison of observed and predicted eGFRs at last follow-up. Results Patients treated with tolvaptan had lower eGFR slopes from baseline (mean±SD, −2.20±2.18 ml/min per 1.73 m 2 per year) and from month 1 (mean±SD, −1.97±2.44 ml/min per 1.73 m 2 per year) compared with controls (mean±SD, −3.50±2.09 ml/min per 1.73 m 2 per year; P <0.001), and lower risk of a 33% reduction in eGFR (risk ratio, 0.63; 95% confidence interval, 0.38 to 0.98 from baseline; risk ratio, 0.53; 95% confidence interval, 0.31 to 0.85 from month 1). Annualized eGFR slopes of patients treated with tolvaptan did not change during follow-up and differences between observed and predicted eGFRs at last follow-up increased with duration of treatment. Conclusions Follow-up for up to 11.2 years (average 4.6 years) showed a sustained reduction in the annual rate of eGFR decline in patients treated with tolvaptan compared with controls and an increasing separation of eGFR values over time between the two groups.

Background Hepatic steatosis is strongly associated with cardiovascular disease in the general population. Whether recurrent or de novo, it can occur in the allograft, but the impact on survival and long-term clinical outcomes remains unclear. In this study, we aim to determine both the frequency and impact of allograft steatosis on long-term posttransplant outcomes. Methods A retrospective review of 588 adult liver transplant (LT) recipients (1999-2006) was performed. Cox regression analysis (time-dependent) was used to evaluate differences in time to steatosis post-LT, patient survival, and cardiovascular outcomes. Results Mean age 51.9 ± 10.6 years, 64.6% males, underlying nonalcoholic steatohepatitis (NASH) (9.4%), previous tobacco (52%), pre-LT diabetes mellitus (30.3%), pre-LT hypertension (23.2%), and known cardiovascular disease (9.7%). Overall, 254 recipients developed allograft steatosis (at 10 years: 77.6% NASH recipients, 44.7% Non-NASH recipients). Risk factors for allograft steatosis were female sex (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.09-2.00; P = 0.014), hepatitis C virus diagnosis (HR, 2.49; 95% CI, 1.77-3.94; P < 0.001), and time-dependent BMI (per unit: HR, 1.08; 95% CI, 1.05-1.10; P < 0.001). Allograft steatosis was not associated with post-LT survival (P = 0.25) nor cardiovascular events (HR, 1.08; 95% CI, 0.73-1.59; P = 0.70). Underlying NASH associated with cardiovascular events (HR, 2.04; 95% CI, 1.37-3.04; P < 0.001). Conclusions Allograft steatosis is common but not associated with survival or cardiovascular events in this study. Larger prospective studies are needed to better define the natural history of allograft steatosis.

Objectives The ideal frequency of cervical cancer screening in women with solid organ transplants (SOTs) remains to be determined. We aimed to assess the longitudinal rates of cytologic and histologic cervical abnormalities in women after SOT. Methods We retrospectively reviewed health records of women aged 18 to 60 years who received their first kidney, liver, pancreas, or combination transplant at Mayo Clinic (Rochester, Minnesota) from 1995 through 2011. Patient demographics, cervical cytology and histology, and high-risk human papillomavirus (hrHPV) testing data were abstracted. All women included in the study had documentation of at least 1 cervical cytologic assessment after SOT. Cumulative incidence of abnormal cytology or histology was estimated using the Kaplan-Meier method. Results In total, 459 women (mean age at SOT, 43.9 years) were included in the study. Pre-SOT cytology was benign in 226 (97.4%) of 232 patients with available results. During follow-up, 9 women had cervical intraepithelial neoplasia grade 3 or higher (CIN3+) histology. The cumulative incidence of CIN3+ was 0.2% (95% confidence interval [CI], 0%–0.6%) at 1 year after SOT, 0.7% (95% CI, 0%–1.5%) at 2 years, 1.9% (95% CI, 0.5%–3.3%) at 5 years, and 3.1% (95% CI, 0.4%–5.7%) at 10 years. At the time of the first post-SOT cervical cytology, a greater proportion of women who were hrHPV positive had abnormal findings compared with hrHPV-negative women (10/15 [66.7%] vs 1/71 [1.4%]; p < .001). Conclusions The cumulative incidence of CIN3+ in the first 5 years after SOT approximates the level of risk for which annual cytologic assessment has been recommended.