Citations

INTRODUCTION: Female patients being evaluated for liver transplantation (LT) routinely undergo a gynecologic exam including cervical cancer screening. The prevalence of cervical cytologic abnormalities in this high risk population is unknown. Our study determines prevalence of cervical cytologic abnormalities, HPV positive status, and risk factors for abnormal cervical screening for this population. METHODS: With Institutional review board approval, we reviewed 375 charts of women undergoing evaluation for LT from 2008‒2013 at Mayo Clinic Florida. We recorded demographics, Pap smear results, High risk HPV positive results, and co-morbid conditions. Univariate analysis was done to determine risk factors. We compared the result of the LT group to the general female population getting cervical cancer screening during the same time period. RESULTS: 37 of 375 (9.86%) LT patients had abnormal Pap smear, compared to 1784 of 26118 (6.83%) of the general population patients (p < 0.01). Among LT patients with cervical cytologic abnormalities, 40.5% were ASCUS, HPV positive (64.8% for non-LT patients), 29.7% were LSIL (28.1% for non-LT patients), 5.4% were HSIL (6.7% for non-LT patients) and 24.3% were cytology negative with HPV positive (0.2% for non-LT patients, p < 0.05). Younger age and presence of hypertension were associated with higher risk of having an abnormal cervical cytology or positive HPV status among LT patients. CONCLUSION: Patients undergoing evaluation for LT have increased prevalence of abnormal cervical cytology, or a positive High risk HPV test. Gynecologic surveillance for this high risk population is recommended.

Study Design: A multicentered retrospective case series. Objective: To determine the incidence and circumstances surrounding the development of a symptomatic postoperative epidural hematoma in the cervical spine. Methods: Patients who underwent cervical spine surgery between January 1, 2005, and December 31, 2011, at 23 institutions were reviewed, and all patients who developed an epidural hematoma were identified. Results: A total of 16 582 cervical spine surgeries were identified, and 15 patients developed a postoperative epidural hematoma, for a total incidence of 0.090%. Substantial variation between institutions was noted, with 11 sites reporting no epidural hematomas, and 1 site reporting an incidence of 0.76%. All patients initially presented with a neurologic deficit. Nine patients had complete resolution of the neurologic deficit after hematoma evacuation; however 2 of the 3 patients (66%) who had a delay in the diagnosis of the epidural hematoma had residual neurologic deficits compared to only 4 of the 12 patients (33%) who had no delay in the diagnosis or treatment ( P = .53). Additionally, the patients who experienced a postoperative epidural hematoma did not experience any significant improvement in health-related quality-of-life metrics as a result of the index procedure at final follow-up evaluation. Conclusion: This is the largest series to date to analyze the incidence of an epidural hematoma following cervical spine surgery, and this study suggest that an epidural hematoma occurs in approximately 1 out of 1000 cervical spine surgeries. Prompt diagnosis and treatment may improve the chance of making a complete neurologic recovery, but patients who develop this complication do not show improvements in the health-related quality-of-life measurements.

Background and ObjectivesCurrent randomized controlled trials are investigating the outcomes of non‐surgical treatment for patients with ductal carcinoma in situ (DCIS). We sought to evaluate pre‐operative factors associated with no residual disease at definitive resection following a core needle biopsy (CNB) diagnosis of DCIS.MethodsEight hundred and thirty‐four operations for DCIS were performed at our institution between January 2004 and October 2014. We evaluated patient and biopsy tumor characteristics to determine pre‐operative factors associated with no residual disease at surgical resection using uni‐ and multivariable analyses.ResultsSixty‐nine patients (8%) had no residual disease on final pathology. On multivariable analysis, low‐ or intermediate‐grade lesions, <1 cm in size on mammography, and lesions where ≥90% of calcifications were removed correlated with finding no residual disease on final pathology, c‐statistic 0.84. Of the 14 patients with all three low‐risk factors, 36% had no residual disease on final pathology.ConclusionsAlthough our multivariable analysis performed well, its clinical utility would be limited as we were unable to identify a subset of patients with DCIS in whom the probability of finding no residual disease is low enough to consider routine use of non‐surgical management.

3 Background: There is a clear need to develop a clinically relevant molecular subtyping approach for prostate cancer. We hypothesized that prostate cancer can be subtyped based on luminal versus basal lineage. Methods: We applied the PAM50 classifier, which is used clinically to identify luminal and basal cancers in breast cancer, to subtype a total of 3,782 prostate cancer samples using a high-density microarray platform run in a CLIA-certified laboratory. We examined the associations of these subtypes and clinical outcomes. Results: We demonstrate that PAM50 segregates prostate cancer into three reproducible subtypes in both retrospective cohorts and on prospective validation: luminal A (33.3%-34.3%), luminal B (28.5%-32.6%), and basal (34.1%-37.1%). Luminal B prostate cancers exhibited the worst clinical prognoses, followed by basal and luminal A subtypes (10-year biochemical recurrence-free survival: 29/39/41%; distant metastasis-free survival: 53/73/73%; prostate cancer-specific survival: 78/86/89%; overall survival: 69/80/82% respectively) on both univariable and multivariable analyses accounting for standard clinicopathologic prognostic factors. Known luminal lineage markers, such as NKX3.1 and KRT18, and the basal lineage CD49f signature, were enriched in luminal- and basal-like cancers respectively, demonstrating the connection between these subtypes and established prostate cancer biology. While both luminal-like subtypes were associated with increased AR expression and signaling, only luminal B prostate cancers were significantly associated with post-operative response to androgen deprivation therapy (ADT) in a subset analysis matching patients based on clinicopathologic variables (interaction p = 0.006, luminal B 10-year metastasis: 33% (treated) vs. 55% (untreated), non-luminal B: 37% (treated) vs. 21% (untreated)). Conclusions: These findings contribute novel insight into the biology of prostate cancer, and provide translatable clinical tools for personalizing post-operative ADT for patients with prostate cancer. Similar to breast cancer, these findings suggest that luminal/basal subtyping may be useful in treatment selection in prostate cancer.

ABSTRACTDecay of the HIV reservoir is slowed over time in part by expansion of the pool of HIV-infected cells. This expansion reflects homeostatic proliferation of infected cells by interleukin-7 (IL-7) or antigenic stimulation, as well as new rounds of infection of susceptible target cells. As novel therapies are being developed to accelerate the decay of the latent HIV reservoir, it will be important to identify interventions that prevent expansion and/or repopulation of the latent HIV reservoir. Our previous studies showed that HIV protease cleaves the host protein procaspase 8 to generate Casp8p41, which can bind and activate Bak to induce apoptosis of infected cells. In circumstances where expression of the anti-apoptotic protein BCL2 is high, Casp8p41 instead binds BCL2, and cell death does not occur. This effect can be overcome by treating cells with the clinically approved BCL2 antagonist venetoclax, which prevents Casp8p41 from binding BCL2, thereby allowing Casp8p41 to bind Bak and kill the infected cell. Here we assess whether the events that maintain the HIV reservoir are also antagonized by venetoclax. Using the J-Lat 10.6 model of persistent infection, we demonstrate that proliferation and HIV expression are countered by the use of venetoclax, which causes preferential killing of the HIV-expressing cells. Similarly, during new rounds of infection of primary CD4 T cells, venetoclax causes selective killing of HIV-infected cells, resulting in decreased numbers of HIV DNA-containing cells.IMPORTANCECure of HIV infection requires an intervention that reduces the HIV reservoir size. A variety of approaches are being tested for their ability to impact HIV reservoir size. Even if successful, however, these approaches will need to be combined with additional complementary approaches that prevent replenishment or repopulation of the HIV reservoir. Our previous studies have shown that the FDA-approved BCL2 antagonist venetoclax has a beneficial effect on the HIV reservoir size following HIV reactivation. Here we demonstrate that venetoclax also has a beneficial effect on HIV reservoir size in a model of homeostatic proliferation of HIV as well as in acute spreading infection of HIV in primary CD4 T cells. These results suggest that venetoclax, either alone or in combination with other approaches to reducing HIV reservoir size, is a compound worthy of further study for its effects on HIV reservoir size.

Background: Oblique injuries are known to be a common cause of time out of play for professional baseball players, and prior work has suggested that injury rates may be on the rise in Major League Baseball (MLB). Purpose: To better understand the current incidence of oblique injuries, determine their impact based on time out of play, and to identify common injury patterns that may guide future injury prevention programs. Study Design: Descriptive epidemiological study. Methods: Using the MLB Health and Injury Tracking System, all oblique injuries that resulted in time out of play in MLB and Minor League Baseball (MiLB) during the 2011 to 2015 seasons were identified. Player demographics such as age, position/role, and handedness were included. Injury-specific factors analyzed included the following: date of injury, timing during season, days missed, mechanism, side, treatment, and reinjury status. Results: A total of 996 oblique injuries occurred in 259 (26%) MLB and 737 (74%) MiLB players. Although the injury rate was steady in MiLB, the MLB injury rate declined ( P = .037). A total of 22,064 days were missed at a mean rate of 4413 days per season and 22.2 days per injury. The majority of these occurred during batting (n = 455, 46%) or pitching (n = 348, 35%), with pitchers losing 5 days more per injury than batters ( P < .001). The leading side was injured in 77% of cases and took 5 days longer to recover from than trailing side injuries ( P = .009). Seventy-nine (7.9%) players received either a corticosteroid or platelet-rich plasma injection, and the mean recovery time was 11 days longer compared with those who did not receive an injection ( P < .001). Conclusion: Although the rate of abdominal oblique injuries is on the decline in MLB, this is not the case for MiLB, and these injuries continue to represent a significant source of time out of play in professional baseball. The vast majority of injuries occur on the lead side, and these injuries result in the greatest amount time out of play. The benefit of injections for the treatment of oblique injuries remains unknown.

Abstract Background: The utility of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is controversial. We aimed to identify factors associated with elevated AFP and define the patients for whom AFP is effective for surveillance. Methods: Data from the NCI Early Detection Research Network phase II HCC biomarker study (233 early-stage HCC and 412 cirrhotic patients) were analyzed. We analyzed 110 early-stage HCC and 362 cirrhotic hepatitis C virus (HCV) patients for external validation. Sensitivity, specificity, and area under the ROC curve (AUC) for HCC were calculated. Results: HCV etiology, non-White race, and serum alanine transaminase (ALT) predicted elevated AFP in cirrhotics. Non-White race and ALT predicted elevated AFP in HCC patients. Higher AUC of AFP for HCC was noted in patients with HBV (0.85) and alcohol (0.84), whereas it was lower in patients with hepatitis C virus (HCV; 0.80) and nonviral/alcohol etiology (0.76). The AUC was higher in HCV patients with serum ALT ≤40 U/L than patients with serum ALT &gt;40 U/L (0.91 vs. 0.75, P &lt; 0.01). At 90% specificity, the sensitivity of AFP increased from 44% to 74% in Whites with HCV and from 50% to 85% in non-Whites with HCV. There was a trend toward higher AUC in HCV patients with serum ALT ≤40 U/L than those with serum ALT &gt;40 U/L (0.79 vs. 0.69, P = 0.10) in the validation cohort. Conclusions: The satisfactory performance of AFP in HCV patients with normal ALT should be further validated. Impact: The AFP may serve as a valuable surveillance test in HCV patients with normal ALT. Cancer Epidemiol Biomarkers Prev; 26(7); 1085–92. ©2017 AACR.