Association between hospital volume and receipt of treatment and survival in patients with glioblastoma

The relation between hospital volume and outcomes for patients with glioblastoma is unknown. We undertook this study to determine the effect of hospital volume on treatment received and its effect on survival in patients with glioblastoma. We included patients from the National Cancer Database diagnosed with a glioblastoma from 2006 to 2013. Hospital volume was calculated by examining the treating facilities average number of cases per year and grouping them into tertiles: (low?<?9.25, medium 9.26–23.88, and high?≥?23.39). Treatment was defined as receiving any type of therapeutic surgery, radiation or chemotherapy. Using regression models we examined the relation between hospital volume to treatment received and survival with adjustment for clinical, socioeconomic and institutional factors. The study included 68,726 patients of which 91.8% received treatment. Among patients diagnosed at low volume facilities, 90.1% received treatment versus 94.2% in high volume facilities (p?<?0.0001). Compared to low volume centers, the odds ratio of receiving any treatment was 1.01 (CI 95% CI: 0.95–1.09) and 1.43 (95% CI: 1.31–1.55) for medium volume and high volume facilities, respectively. On multivariate analysis for survival among those who received treatment, the hazard of mortality was decreased at high volume (HR 0.92, 95% CI 0.89–0.94) facilities compared to low volume facilities. Patients diagnosed with glioblastoma at a high volume facility (≥23.39 cases per year) have an increased likelihood of receiving treatment. Furthermore, glioblastoma patients may significantly improve their survival by choosing to receive care at a high-volume hospital.     

Analysis of Reported Adverse Events with Uterine Artery Embolization for Leiomyomas

Study Objective

To analyze and investigate reports associated with uterine artery embolization used for treatment of myomas using this database.

Concentration-dependent dual effect of thrombin on impaired growth/apoptosis or mitogenesis in tumor cells

Because thrombin-treated tumor cell-induced metastasis increases tumor nodule volume(12) greater than nodule number, we studied the effect of thrombin on tumor cell growth in vitro and in vivo (murine B16F10 melanoma, human HCT8 colon carcinoma, DU145 prostate carcinoma). Tumor cell growth was measured after 3 to 7 days in 1% fetal calf serum (FCS) + RPMI 1640. We found that, whereas relatively low concentrations of thrombin, 0.1 to 0.5 U/mL (1-5 nmol/L) enhance tumor cell growth in vitro approximately 2- to 3-fold, higher concentrations, 0.5 to 1 U/mL (5-10 nmol/L) impaired cell growth approximately 2- to 4-fold. Impaired cell growth was associated with cell cycle arrest at G(2)M and increased pre-G(o) DNA, as well as apoptosis, measured by tumor cell binding to Annexin V and propidium iodide. Apoptosis was reversed with the general caspase inhibitor, FK-011. The enhancing and inhibiting effects were specific for thrombin (reversed with inactive diisopropyl-fluorophosphate [DFP]-thrombin) and mediated via the protease-activated receptor 1 (PAR-1). PAR-1 activation was demonstrated by (1) use of a cell line, B16F10, devoid of the 3 other thrombin receptors, PAR-3, PAR-4, and GPIb; and (2) greater sensitivity of PAR-1 transfected B16F10 and HCT8 cells to impaired cell growth/apoptosis, 3- and 14-fold, respectively. Thus, thrombin has a bimodal effect on PAR-1 in tumor cells: enhanced growth at low concentration, impaired growth/apoptosis at higher concentration.     

Targeted treatment and new agents in peripheral T-cell lymphoma

Mature T-cell and NK-cell lymphomas are increasingly being recognized as unique biological entities distinguishable from other forms of lymphomas. Treatment paradigms developed for B-cell lymphomas are considered inadequate for application to these diseases, as indicated by the poor outcome of these patients with the overall 5-year survival remaining below 30% for most histologies. There is a tremendous need for newer treatment options both in the upfront and relapsed setting for T-cell lymphomas. In recent years, there has been a plethora of new targeted agents that have shown promising activity in T-cell lymphomas. The most notable is the novel antifolate pralatrexate that has been approved for the treatment of relapsed and refractory T-cell lymphoma. Other agents include histone deacetylase inhibitors (vorinostat, romidepsin, belinostat), proteosome inhibitors (bortezomib), immunomodulatory agents (lenalidomide), nucleoside analogs (gemcitabine, nalarabine) and targeted antibodies. An improved understanding of the molecular pathogenesis of T-cell lymphomas will help define the role of these agents in the treatment paradigms of T-cell lymphomas both as single agents and as rationally designed combinations and will lead to curative treatments for these difficult diseases.     

Reversible Blindness as Presenting Manifestation of Severe Diabetic Ketoacidosis

The presenting symptoms of diabetic ketoacidosis (DKA) include abdominal pain, polyuria and nausea. Diabetes has well known chronic ocular complications like glaucoma, cataracts and retinopathy. We report a case of reversible blindness as a presenting manifestation of DKA that has been reported in literature only 3 times previously. Our objective is to highlight a rare manifestation of a common disease. A 59-year-old male presented with painless vision loss for 3 days and was found to have DKA. The blindness was completely reversed with insulin and bicarbonate treatment. The dramatic presentation and reversibility of blindness was found to be intimately tied with the pH of the patient's serum. Our report gives mechanistic insight for this interesting condition. Clinicians should be aware of reversible blindness as a complication of DKA. Timely correction of the severe acidosis and other metabolic disturbances of DKA may be instrumental in preventing permanent vision loss.     

Significant association of high-risk human papillomavirus (HPV) but not of p53 polymorphisms with oral squamous cell carcinomas in Malaysia

Purpose  

The purpose of this study was to evaluate the role of HPV and p53 polymorphisms in oral squamous cell carcinomas (OSCC) affecting Malaysian population.