Decipher correlation patterns post prostatectomy: initial experience from 2 342 prospective patients.

BACKGROUND: Currently, there are multiple commercially available RNA-based biomarkers that are Medicare approved and suggested for use by the National Comprehensive Cancer Network guidelines. There is uncertainty as to which patients benefit from genomic testing and for whom these tests should be ordered. Here, we examined the correlation patterns of Decipher assay to understand the relationship between the Decipher and patient tumor characteristics. METHODS: De-identified Decipher test results (including Decipher risk scores and clinicopathologic data) from 2 342 consecutive radical prostatectomy (RP) patients tested between January and September 2015 were analyzed. For clinical testing, tumor specimen from the highest Gleason grade was sampled using a 1.5 mm tissue punch. Decipher scores were calculated based on a previously locked model. Correlations between Decipher score and clinicopathologic variables were computed using Spearman's rank correlation. Mixed-effect linear models were used to study the association of practice type and Decipher score. The significance level was 0.05 for all tests. RESULTS: Decipher score had a positive correlation with pathologic Gleason score (PGS; r=0.37, 95% confidence interval (CI) 0.34-0.41), pathologic T-stage (r=0.31, 95% CI 0.28-0.35), CAPRA-S (r=0.32, 95% CI 0.28-0.37) and patient age (r=0.09, 95% CI 0.05-0.13). Decipher reclassified 52%, 76% and 40% of patients in CAPRA-S low-, intermediate- and high-risk groups, respectively. We detected a 28% incidence of high-risk disease through the Decipher score in pT2 patients and 7% low risk in pT3b/pT4, PGS 8-10 patients. There was no significant difference in the Decipher score between patients from community centers and those from academic centers (P=0.82). CONCLUSIONS: Although Decipher correlated with baseline tumor characteristics for over 2 000 patients, there was significant reclassification of tumor aggressiveness as compared to clinical parameters alone. Utilization of the Decipher genomic classifier can have major implications in assessment of postoperative risk that may impact physician-patient decision making and ultimately patient management.

Efficacy of post-operative radiation in a prostatectomy cohort adjusted for clinical and genomic risk.

BACKGROUND: To date, there have been no published trials examining the impact of salvage radiation therapy (SRT) in the post-operative setting for prostate cancer (PCa). We conducted a retrospective, comparative study of post-operative radiation following radical prostatectomy (RP) for men with pT3 disease or positive margins (adverse pathological features, APF). METHODS: 422 PCa men treated at four institutions with RP and having APF were analyzed with a primary end point of metastasis. Adjuvant radiation treatment (ART, n=111), minimal residual disease (MRD) SRT (n=70) and SRT (n=83) were defined by PSA levels of <0.2, 0.2-0.49 and ⩾0.5 ng ml(-1), respectively, before radiation therapy (RT) initiation. Remaining 157 men who did not receive additional therapy before metastasis formed the no RT arm. Clinical-genomic risk was assessed by Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) and Decipher. Cox regression was used to evaluate the impact of treatment on outcome. RESULTS: During the study follow-up, 37 men developed metastasis with a median follow-up of 8 years. Both CAPRA-S and Decipher had independent predictive value on multivariable analysis for metastasis (P<0.05). Adjusting for clinical-genomic risk, SRT and no RT had hazard ratios of 4.31 (95% confidence interval, 1.20-15.47) and 5.42 (95% confidence interval, 1.59-18.44) for metastasis compared with ART, respectively. No significant difference was observed between MRD-SRT and ART (P=0.28). Men with low-to-intermediate CAPRA-S and low Decipher value have a low rate of metastatic events regardless of treatment selection. In contrast, men with high CAPRA-S and Decipher benefit from ART, however the cumulative incidence of metastasis remains high. CONCLUSIONS: The decision as to the timing and need for additional local therapy following RP is nuanced and requires providers and patients to balance risks of morbidity with improved oncological outcomes. Post-RP treatment can be safely avoided for men who are low risk by clinical-genomic risk, whereas those at high risk should favor enrollment in clinical trials.

Influence of diabetes and diabetes type on anatomic and visual outcomes following central rein vein occlusion.

PURPOSE: To determine the influence of diabetes and diabetes type on ocular outcomes following central retinal vein occlusion (CRVO). METHODS: Retrospective chart review of all patients evaluated over a 4-year period in a tertiary diabetes eye care center. Ophthalmic findings were recorded including visual acuity and the presence of retinal neovascularization at presentation, after 3-6 months, and at last follow-up. RESULTS: The records of 19,648 patients (13,571 diabetic; 6077 nondiabetic) were reviewed. The prevalence of CRVO in diabetic patients (N=72) and nondiabetic patients (N=27) were 0.5 and 0.4%, respectively. Disc neovascularization (21.3 vs 0.0%, P=0.05) and panretinal photocoagulation (PRP) (48.7 vs 21.4%, P=0.01) were more common in diabetic patients compared with nondiabetic patients. Compared with type 2 diabetic patients, retinal neovascularization (28.6 vs 3.7%, P=0.004) and subsequent PRP (78.6 vs 41.9%, P=0.01) were more likely in type 1 patients. Optic nerve head collateral vessels (CVs) were observed less than half as often (21.4 vs 56.5%, P=0.04) in patients with type 1 diabetes. Presence of optic nerve head CVs at baseline was associated with less likelihood of PRP (14.3 vs 46.1%, P=0.03). CONCLUSIONS: In this cohort, the rates of CRVO in diabetic and nondiabetic patients were similar to previously published population-based studies. Following CRVO, diabetic patients had higher rates of disc neovascularization and were more likely to require subsequent PRP than nondiabetic patients. As compared with CRVO patients with type 2 diabetes, patients with type 1 diabetes and CRVO had worse anatomic outcomes with substantially increased risks of retinal neovascularization and PRP; however, final visual acuity outcomes were similar.

Peripheral insulin and brain structure in early Alzheimer disease.

OBJECTIVE: Accumulating evidence suggests insulin and insulin signaling may be involved in the pathophysiology of Alzheimer disease (AD). The relationship between insulin-mediated glucoregulation and brain structure has not been assessed in individuals with AD. METHODS: Nondemented (Clinical Dementia Rating [CDR] 0, n = 31) and early stage AD (CDR 0.5 and 1, n = 31) participants aged 65 years and older had brain MRI to determine whole brain and hippocampal volume and 3-hour IV glucose tolerance tests to determine glucose and insulin area under the curve (AUC). Linear regression models were used to assess the relationship of insulin and glucose with brain volume, cognition, and dementia severity. RESULTS: In early AD, insulin and glucose AUCs were related to whole brain (insulin beta = 0.66, p < 0.001; glucose beta = 0.45, p < 0.01) and hippocampal volume (insulin beta = 0.42, p < 0.05; glucose beta = 0.46, p < 0.05). These relationships were independent of age, sex, body mass index, body fat, cardiorespiratory fitness, physical activity, cholesterol, and triglycerides. Insulin AUC, but not glucose, was associated with cognitive performance in early AD (beta = 0.40, p = 0.04). Insulin AUC was associated with dementia severity (Pearson r = -0.40, p = 0.03). Glucose and insulin were not related to brain volume or cognitive performance in nondemented individuals. CONCLUSIONS: Increased peripheral insulin is associated with reduced Alzheimer disease (AD)-related brain atrophy, cognitive dysfunction, and dementia severity, suggesting that insulin signaling may play a role in the pathophysiology of AD.

[Branchial paraganglioma. A case of carotid paraganglioma and review of the literature]. / Les paragangliomes branchiaux. A propos d'un cas de paragangliome carotidien et revue de la littérature.

We report the case of a 58-year-old man hospitalized for generalized seizures. A grade II glioma of the left frontotemporal region was diagnosed on brain CT scan and stereotaxic biopsy results. Radiotherapy was successful in treating this glioma. A glomus tumor of the left carotid was discovered by duplex Doppler examination of the carotid and confirmed on arteriography. Resection was performed to the adventitia. Branchial glomus tumors are rare, often benign tumors. The carotid is a common localization. Surgery is often indicated due to the risk of local invasion. Surgical procedure varies according to the size and localization of the tumor. This case demonstrates that glomus tumor of the carotid can coexist with a frontotemporal glioma.

Budd-Chiari syndrome associated with antiphospholipid antibodies in a child: report of a case and review of the literature.

Budd-Chiari syndrome, hypertension, and thrombocytopenia developed in a 6-year-old girl as manifestations of primary antiphospholipid antibody syndrome (APS). She improved with systemic corticosteroid and anticoagulation therapy. Anticardiolipin antibodies were found in the patient, her mother and 3 siblings, suggesting the importance of genetic factors. The clinical features of an APS in children is reviewed.

Pentigetide nasal solution: a multicenter study evaluating efficacy and safety in patients with seasonal allergic rhinitis.

The safety and efficacy of pentigetide (Pentyde) nasal solution, administered as 1 mg into each nostril four times daily, was compared with placebo for controlling symptoms associated with seasonal allergic rhinitis. This was a randomized, multicenter, double-blind, parallel-group trial involving 431 patients divided equally between pentigetide and placebo treatment. The study was conducted during the 1986 spring allergy season and consisted of 1 week of baseline followed by 2 weeks of treatment. Physicians evaluated the frequency and severity of nasal symptoms at study entry (day 1) and the final visit (day 22). Physicians and patients assessed the global condition of the patient at the end of the study and patients also recorded the severity of symptoms in a daily diary. Pentigetide-treated patients showed a statistically significant greater reduction in the frequency (P = .004) and severity (P = .05) of total nasal symptom score (sneezing, nasal congestion, and rhinorrhea) and in the individual nasal symptom scores compared with placebo-treated patients. Diary results showed consistently lower total nasal symptom scores on each treatment day for pentigetide-treated patients (P = .02). Both the physicians and patients globally rated more pentigetide-treated patients improved than placebo-treated patients. The incidence and types of adverse experiences were similar between treatment groups and there were no reports of sedation or fatigue in the pentigetide group. No clinically significant changes occurred for laboratory tests, physical examination parameters or vital sign measurements. Pentigetide nasal solution was safe and effective for the treatment of seasonal allergic rhinitis.

Desensitization to trimethoprim sulfamethoxazole in patients with acquired immune deficiency syndrome and Pneumocystis carinii pneumonia.

In three of eight patients with the acquired immune deficiency syndrome the Pneumocystis carinii pneumonia treated with intravenous trimethoprim sulfamethoxazole, drug-related reactions occurred 9, 10, and 13 days after therapy. The symptom complex consisted of a maculopapular eruption, fever, eosinophilia, and leukopenia. Oral desensitization with graded doses of trimethoprim sulfamethoxazole was successfully achieved in two of the three patients.

Doubling time and annual doubling rate of human prostatic cancer.

The doubling time (DT) of human prostatic cancer is calculated for the first time; its various parameters and the relative importance of each are reviewed. A crude volume-doubling time (DTcv), a theoretical doubling of the number of cells (DTt), and an annual doubling rate (ADR), are defined and calculated for each of 12 patients who had undergone needling of the prostate for diagnostic purposes and in whom tumor cells were implanted in the track of the biopsy needle and had grown into a subcutaneous perineal nodule. The harmonic average DTcv was six days and DTt eight days, and the average ADR was 45 doublings per year. From the study of the calculated DTs and ADRs, it became obvious that the 12 patients fell into three distinct groups: Group I = slow tumor growth rate, an average ADR of 9 doublings per year, and a harmonic average DTt of forty days; Group II = medium tumor growth rate, an average ADR of 35 doublings/year, and a harmonic average DTt of ten days; and Group III = rapid tumor growth rate, an average ADR of 100 doublings/year, and a harmonic average DTt of four days.

Factorial rating system for comparative efficacy of antiasthmatic medication: a multicentric study report.

Faced with 1-year daily medication diaries from over 300 patients, each documenting the use of from one to five medications a day, we found it was necessary to devise a system which would reduce this data into a form which would allow a meaningful interpretation of changes of medications in a single patient or group of patients. Since the medications were principally steroids, beta agonists, or xanthines, representative agents were chosen as the standard for each class and the other medications were rated against them. A conversion factor was then determined to allow comparison between classes. Each medication taken by a patient could now be expressed as a single number and the sum of all the medications would be the individual's Asthma Medication Index. The AMI allowed (i) evaluation of a single patient over time, (ii) comparison of different patients at any single point or over a period of time, and (iii) evaluation of entire groups of patients over time as was the case in our evaluation of Zaditen. Application of the system allowed the differentiation of two therapeutic agents versus placebo during a 1-year study, revealing excellent correlation with the physician's global assessment of the patient's improvement. With proper modification of the basic drug groups and intergroup factor relationship, the Index can be adapted to any disease state where a change in concomitant medication is an indicator of therapeutic effect.

Circulating autoantibodies to hidden mitochondrial antigenic determinants in mammals.

Autoantibodies to equine cytochrome c and to porcine malic dehydrogenase are shown in equine and porcine serum, respectively, by immunodiffusion. A confluence of arcs between human plasma and rabbit, horse and pig serum against these antigens suggests the presence of antibodies in human plasma to cytochrome c and malic dehydrogenase. The use of tris buffer containing a low concentration of Dodecyl sodium sulfate for cytochrome c and of glycerol for malic dehydrogenase maintains their solubility and enhances their participation in antibody-antigen immunoprecipitation possibly by unravelling the peptide chains and exposing reactive antigenic determinants hidden within the interstices of the cytochrome c and malic dehydrogenase molecules.

A comparison of the bronchodilator and other responses of children to oral treatment with terbutaline tablet and solution: a bioequivalence study.

Terbutaline tablets and oral solution were tested in 16 subjects between the ages of seven and 15 in a double-blind acute cross-over study. Doses of terbutaline were 2.5, 3.75 or 5.0 mg depending upon the weight of each subject. Both formulations produced significant increases in pulmonary function between 15 minutes and five hours after drug administration as measured by FVC and FEV1. The mean maximal increase in FEV1 was 0.60 liters for the tablet and 0.70 liters for the solution. The mean maximal increase in FVC was 0.53 liters for the tablet and 0.67 for the solution. There were significant increases in heart rate following both tablet and solution. The mean increases were statistically significant between two and five hours after drug administration, ranging from two to nine beats/minute for the tablet and eight to 13 beats/minute for the solution. Terbutaline produced no clinically or statistically significant mean changes in systolic or diastolic blood pressure. The responses to tablet and solution did not differ significantly from each other in any parameter. Terbutaline tablet and oral solution were, therefore, bioequivalent.