Effect of Intensive vs Standard Blood Pressure Treatment Upon Erectile Function in Hypertensive Men: Findings From the Systolic Blood Pressure Intervention Trial.

INTRODUCTION: The effect of intensive blood pressure control upon erectile function in men with hypertension, but without diabetes, is largely unknown. AIM: To examine the effects of intensive systolic blood pressure (SBP) lowering on erectile function in a multiethnic clinical trial of men with hypertension. METHODS: We performed subgroup analyses from the Systolic Blood Pressure Intervention Trial ([SPRINT]; ClinicalTrials.gov: NCT120602, in a sample of 1255 men aged 50 years or older with hypertension and increased cardiovascular disease risk. Participants were randomly assigned to an intensive treatment group (SBP goal of <120 mmHg) or a standard treatment group (SBP goal of <140 mmHg). MAIN OUTCOME MEASURE: The main outcome measure was change in erectile function from baseline, using the 5-item International Index of Erectile Function (IIEF-5) total score, and erectile dysfunction ([ED]; defined as IIEF-5 score ≤21) after a median follow-up of 3 years. RESULTS: At baseline, roughly two-thirds (66.1%) of the sample had self-reported ED. At 48 months after randomization, we determined that the effects of more intensive blood pressure lowering were significantly moderated by race-ethnicity (p for interaction = 0.0016), prompting separate analyses stratified by race-ethnicity. In non-Hispanic whites, participants in the intensive treatment group reported slightly, but significantly better change in the IIEF-5 score than those in the standard treatment group (mean difference = 0.67; 95% CI = 0.03, 1.32; P = 0.041). In non-Hispanic blacks, participants in the intensive group reported slightly worse change in the IIEF-5 score than those in the standard group (mean difference = -1.17; 95% CI = -1.92, -0.41; P = 0.0025). However, in non-Hispanic whites and non-Hispanic blacks, further adjustment for the baseline IIEF-5 score resulted in nonsignificant differences (P > 0.05) according to the treatment group. In Hispanic/other participants, there were no significant differences in change in the IIEF-5 score between the two treatment groups (P = 0.40). In a subgroup of 280 participants who did not report ED at baseline, the incidence of ED did not differ in the two treatment groups (P = 0.53) and was without interaction by race-ethnicity. CLINICAL IMPLICATIONS: The effect of intensive treatment of blood pressure on erectile function was very small overall and likely not of great clinical magnitude. STRENGTH & LIMITATIONS: Although this study included a validated measure of erectile function, testosterone, other androgen, and estrogen levels were not assessed. CONCLUSION: In a sample of male patients at high risk for cardiovascular events but without diabetes, targeting a SBP of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in statistically significant effects on erectile function that differed in accordance with race-ethnicity, although the clinical importance of the differences may be of small magnitude. Foy CG, Newman JC, Russell GB, et al. Effect of Intensive vs Standard Blood Pressure Treatment Upon Erectile Function in Hypertensive Men: Findings From the Systolic Blood Pressure Intervention Trial. J Sex Med 2020;17:238-248.

Temporal trends in fluid management with incremental hemodialysis
.

BACKGROUND: Incremental hemodialysis (HD) is seldom prescribed in the United States. This study describes longitudinal changes in volume management in patients with incident end-stage kidney disease (ESKD) initiated on bi-weekly (twice a week) HD, later converted to thrice-weekly HD. MATERIALS AND METHODS: 23 patients (mean age 65.6 years, 48% male, and 30% black) were included. Repeated measurement analysis of regression was used to test for differences in interdialytic weight gain (IDWG) and ultrafiltration rate (UFR) over three dialysis periods: the first 3 months of bi-weekly HD, the last 3 months of bi-weekly HD, and the first 3 months of thrice-weekly HD. RESULTS: The mean transition time to thrice-weekly HD was 332.9 days. Compared to the first 3 months of HD, the IDWG and UFR increased by 0.6 kg and 2.2 mL/kg/h in the last 3 months of bi-weekly HD (p = 0.02 and 0.009, respectively) and by 0.7 kg and 2.1 mL/kg/h in the first 3 months of thrice-weekly HD (p = 0.002). The average proportion of patients with IDWG > 5.7% of the dry weight was 0% in the first 3 months of bi-weekly HD, 12% in the last 3 months of bi-weekly HD, and 4% in the first 3 months of thrice-weekly HD; while the average proportion of patients with UFR > 10 mL/kg/h was 16%, 39%, and 25%, respectively. CONCLUSION: Fluid management in incident-ESKD patients receiving bi-weekly HD deteriorates prior to conversion to thrice-weekly HD. Further studies are needed to optimize the prescription of incremental HD.

Molecular determinants of susceptibility to oncolytic vesicular stomatitis virus in pancreatic adenocarcinoma.

BACKGROUND: M protein mutant vesicular stomatitis virus (M51R-VSV) has oncolytic properties against many cancers. However, some cancer cells are resistant to M51R-VSV. Herein, we evaluate the molecular determinants of vesicular stomatitis virus (VSV) resistance in pancreatic adenocarcinoma cells. METHODS: Cell viability and the effect of ß-interferon (IFN) were analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Gene expression was evaluated via microarray analysis. Cell infectability was measured by flow cytometry. Xenografts were established in athymic nude mice and treated with intratumoral M51R-VSV. RESULTS: Four of five pancreatic cancer cell lines were sensitive to M51R-VSV, whereas Panc 03.27 cells remained resistant (81 ± 3% viability 72 h after single-cycle infection). Comparing sensitive MiaPaCa2 cells with resistant Panc 03.27 cells, significant differences in gene expression were found relating to IFN signaling (P = 2 × 10(-5)), viral entry (P = 3 × 10(-4)), and endocytosis (P = 7 × 10(-4)). MiaPaCa2 cells permitted high levels of VSV infection, whereas Panc 03.27 cells were capable of resisting VSV cell entry even at high multiplicities of infection. Extrinsic ß-IFN overcame apparent defects in IFN-mediated pathways in MiaPaCa2 cells conferring VSV resistance. In contrast, ß-IFN decreased cell viability in Panc 3.27 cells, suggesting intact antiviral mechanisms. VSV-treated xenografts exhibited reduced tumor growth relative to controls in both MiaPaCa2 (1423 ± 345% versus 164 ± 136%; P < 0.001) and Panc 3.27 (979 ± 153% versus 50 ± 56%; P = 0.002) tumors. Significant lymphocytic infiltration was seen in M51R-VSV-treated Panc 03.27 xenografts. CONCLUSIONS: Inhibition of VSV endocytosis and intact IFN-mediated defenses are responsible for M51R-VSV resistance in pancreatic adenocarcinoma cells. M51R-VSV treatment appears to induce antitumor cellular immunity in vivo, which may expand its clinical efficacy.

Patterns of failure after treatment of atypical meningioma with gamma knife radiosurgery.

Atypical meningiomas have poor local control with emerging literature indicating the use of radiosurgery in treatment. The purpose of this study was to evaluate clinical outcomes including local control and failure pattern after Gamma Knife radiosurgery (GKRS) and factors that may affect these outcomes. Between 1999 and 2008, 24 patients were treated with GKRS as either primary or salvage treatment for pathologically proven atypical meningiomas. Treatment failures were determined by serial magnetic resonance imaging. A median marginal dose of 14 Gy was used (range 10.5-18 Gy). Overall local control rates at 1, 2, and 5 years were 75, 51, and 44%, respectively. With median follow-up time of 42.5 months, 14 of 24 patients experienced a treatment failure at time of last follow-up. Eight recurrences were in-field, four were marginal failures, and two were distant failures. Wilcoxon analysis revealed that the conformality index (CI) was a significant predictor of local recurrence (P = 0.04). CI did not predict for distant recurrences (P = 0.16). On multivariate analysis evaluating factors predicting progression free survival, dose >14 Gy was found to be statistically significant (P = 0.01). There appears to be a dose response using GKRS beyond 14 Gy but given the suboptimal local control rates in this study, higher doses may still be needed to obtain better local control.

Low-dose adjuvant interferon for stage III malignant melanoma.

The role of interferon as adjuvant therapy in stage III melanoma has recently been questioned. Prospective randomized studies have shown conflicting results regarding the efficacy of adjuvant treatment. The purpose of this study was to examine the use of low-dose adjuvant interferon alpha2-b (IFN) in stage III melanoma patients treated at a single institution. This study was a retrospective analysis of 60 stage III melanoma cases from Wake Forest University treated between 1983 and 1998. Cases were identified via the tumor registry. All patients underwent standard lymphadenectomy after diagnosis. After recovery from surgery patients were offered low-dose IFN (3 million units subcutaneous TIW for 1 month and then 6 million units subcutaneous TIW for 11 months) as adjuvant therapy for stage III melanoma. The patients were followed up jointly by medical and surgical oncology. There were 39 male and 21 female patients with mean age of 60.0 (range 37-89) years. The average number of positive nodes was 3.6 (median = 1) for the treated group and 1.8 (median = 1) for those untreated (P = 0.71). The average tumor thickness was similar between groups: 4.71 versus 4.88 mm for the IFN and observation groups respectively. The IFN group (N = 25) that received low-dose treatment had a median survival of 7.9 years with a 5-year survival rate of 69 per cent. The 35 cases that did not receive interferon had a median survival of 6.5 years and a 5-year survival rate of 52 per cent. These survival rates were not significantly different (P = 0.91). The median disease-free survival for patients who did not receive IFN treatment was 2.4 years and 1.4 years for the treated group (P = 0.19). The data show that there was similar survival for those who did and did not receive the low-dose IFN treatment. Although only large prospective trials can conclusively exclude a small survival time this experience suggests that there is no significant survival advantage to low-dose adjuvant IFN therapy for stage III melanoma patients. Hopefully upcoming cooperative group trials will clarify the potential value of adjuvant IFN in this setting. However, although the toxicity of this regimen was mild we suggest that low-dose adjuvant IFN for stage III melanoma should not be utilized outside the setting of a clinical trial.

Risk of catheter-related bloodstream infection in elderly patients on hemodialysis.

BACKGROUND AND OBJECTIVES: Elderly patients require tunneled central vein dialysis catheters more often than younger patients. Little is known about the risk of catheter-related bloodstream infection in this population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study identified 464 patients on hemodialysis with tunneled central vein dialysis catheters between 2005 and 2007 and excluded patients who accrued <21 catheter-days during this period. Outpatient and inpatient catheter-related bloodstream infection data were collected. A Cox proportional hazards regression analysis adjusting for sex, ancestry, comorbidites, dialysis vintage, dialysis unit, immunosuppression, initial catheter site, and first antimicrobial catheter lock solution was performed for risk of catheter-related bloodstream infection between nonelderly (18-74 years) and elderly (≥ 75 years) patients. RESULTS: In total, 374 nonelderly and 90 elderly patients with mean (SD) ages of 54.8 (12.3) and 81.3 (4.9) years and dialysis vintages of 1.8 (3.3) and 1.5 (2.9) years (P=0.47), respectively, were identified. Mean at-risk catheter-days were 272 (243) in nonelderly and 318 (240) in elderly patients. Between age groups, there were no significant differences in initial catheter site, type of catheter lock solution, or microbiology results. A total of 208 catheter-related bloodstream infection events occurred (190 events in nonelderly and 18 events in elderly patients), with a catheter-related bloodstream infection incidence per 1000 catheter-days of 1.97 (4.6) in nonelderly and 0.55 (1.6) in elderly patients (P<0.001). Relative to nonelderly patients, the hazard ratio for catheter-related bloodstream infection in the elderly was 0.33 (95% confidence interval, 0.20 to 0.55; P<0.001) after multivariate analysis. CONCLUSION: Elderly patients on hemodialysis using tunneled central vein dialysis catheters are at lower risk of catheter-related bloodstream infection than their younger counterparts. For some elderly patients, tunneled central vein dialysis catheters may represent a suitable dialysis access option in the setting of nonmaturing arteriovenous fistulae or poorly functioning synthetic grafts.

Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis from small bowel adenocarcinoma.

INTRODUCTION: Peritoneal carcinomatosis (PC) is associated with a dismal prognosis. Small bowel adenocarcinoma is a rare etiology for PC. Due to the rarity, poor prognosis, and lack of standard treatment, we chose to review our experience with this disease process treated with cytoreductive surgery (CS) and intraperitoneal hyperthermic chemotherapy (IPHC). METHODS: From a prospective database of IPHC patients, six patients diagnosed with PC from adenocarcinoma of the small bowel were identified. Between 1995 and 2004 these patients underwent CS and IPHC with Mitomycin C. A retrospective review was performed on these patients with mortality as the primary outcome measure. RESULTS: Three of the six patients in this series are still alive, with a mean follow-up of 19.7 months after treatment with CS and IPHC. Three patients died of disease progression 29, 30, and 45 months after IPHC. Median survival after diagnosis of small bowel adenocarcinoma was 54 months, while median survival after CS and IPHC for PC was 30.1 months. CONCLUSIONS: Small bowel adenocarcinoma with PC remains an unusual therapeutic challenge. Treatment with CS and IPHC is an attractive option for patients in this setting.