Citations

Abstract Background: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. Methods: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR). Results: We observed no significant association between genetic variants and prostate cancer survival. Conclusions: Common genetic variants with large impact on prostate cancer survival were not observed in this study. Impact: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes. Cancer Epidemiol Biomarkers Prev; 24(11); 1796–800. ©2015 AACR.

ABSTRACTNeither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established forCandidaspp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable.Candidaspecies wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007Candida albicans, 186C. dubliniensis, 3,188C. glabratacomplex, 119C. guilliermondii, 493C. krusei, 205C. lusitaniae, 3,136C. parapsilosiscomplex, and 1,016C. tropicalisisolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing ≥97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 μg/ml forC. albicans, 0.12, 0.25, and 0.03 μg/ml forC. glabratacomplex, 4, 2, and 4 μg/ml forC. parapsilosiscomplex, 0.5, 0.25, and 0.06 μg/ml forC. tropicalis, 0.25, 1, and 0.25 μg/ml forC. krusei, 0.25, 1, and 0.12 μg/ml forC. lusitaniae, 4, 2, and 2 μg/ml forC. guilliermondii, and 0.25, 0.25, and 0.12 μg/ml forC. dubliniensis. Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81Candidaisolates with identifiedfksmutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities ofCandidaspp. to caspofungin by reference methodologies is not recommended.

Diabetic ketoacidosis is a life-threatening acute metabolic complication of uncontrolled diabetes. Severe cases of DKA (pH ≤ 7.00, bicarbonate level ≤ 10.0, anion gap > 12, positive ketones, and altered mental status) are commonly encountered in patients with type 1 diabetes and are thought to carry an ominous prognosis. There is not enough information on the clinical course of severely acidotic type 2 diabetes (pH ≤ 6.9) patients with DKA, possibly because this condition is rarely seen in developed countries. In this series, we present 18 patients with type 2 diabetes, DKA, and a pH ≤ 6.9 that presented to a tertiary university hospital over the past 11 years. The objective was to describe their clinical characteristics, the triggering cause, and emphasis on treatment, evolution, and outcomes. The majority of the patients were female (61%). Mean age was 40.66 years (23–59). The patients had been first diagnosed with type 2 diabetes on average 5.27 ± 3.12 years before admission. Glutamic acid decarboxylase (GAD65) antibodies were negative in all patients. The origin of DKA could be attributed to two main causes: treatment omission in 8 (44.4%) patients and infections in 7 (38.8%) patients. The most common symptoms described were general malaise, dyspnea, altered mental status, and abdominal pain. Mean serum glucose on admission was 613.8 ± 114.5 mg/dL. Mean venous pH was 6.84 ± 0.03 with an anion gap of 30.3 ± 2.9 and a venous HCO3level of 3.62 ± 1.35 mmol/L. All patients had acute renal failure on admission, with a mean serum creatinine of 1.57 ± 0.35 mg/dL compared to 0.55 ± 0.21 mg/dL at discharge. All patients received regular insulin infusion, aggressive fluid repletion, and 12 patients (66%) received bicarbonate infusion. Mean total insulin infusion dose was 181.7 ± 90.4 U (on average 0.14 ± 0.05 U/Kg/h). Mean time on infusion was 24.4 ± 12.6 hours. We recorded no mortality in this case series. Mean in-hospital stay was 5.0 ± 4.1 days. In conclusion, very severe DKA in type 2 diabetes is not uncommon in our population, shares many features with non-very-severe cases of DKA (bicarbonate therapy did not make a difference in mortality), and can be managed following standard published or institutional guidelines.

ObjectivesTo determine whether clinical features of bipolar disorder, such as history of psychosis, and cardiovascular disease (CVD) risk factors contribute to a higher risk of CVD among patients with bipolar disorder.MethodsThis cross‐sectional study included a sample of 988 patients with bipolar I or bipolar II disorder or schizoaffective bipolar type confirmed by the Structured Clinical Interview for DSM‐IV‐TR disorders (SCID). Medical comorbidity burden was quantified utilizing the Cumulative Illness Severity Rating Scale (CIRS). This 13‐item organ‐based scale includes cardiac disease severity quantification. Confirmed by medical record review, patients who scored 1 (current mild or past significant problem) or higher in the cardiac item were compared by logistic regression to patients who scored 0 (no impairment), adjusting for CVD risk factors that were selected using a backwards stepwise approach or were obtained from the literature.ResultsIn a multivariate model, age [odds ratio (OR) = 3.03, 95% confidence interval (CI): 1.66–5.54, p < 0.0001], hypertension (OR = 2.43, 95% CI: 1.69–3.55, p < 0.0001), and history of psychosis (OR = 1.48, 95% CI: 1.03–2.13, p = 0.03) were associated with CVD. When CVD risk factors from the literature were added to the analysis, age (OR = 3.19, 95% CI: 1.67–6.10, p = 0.0005) and hypertension (OR = 2.46, 95% CI: 1.61–3.76, p < 0.01) remained significant, with psychosis being at the trend level (OR = 1.43, 95% CI: 0.96–2.13, p = 0.08).ConclusionsThe phenotype of psychotic bipolar disorder may reflect higher illness severity with associated cardiac comorbidity. Further studies are encouraged to clarify the effect of the disease burden (i.e., depression), lifestyle, and treatment interventions (i.e., atypical antipsychotics) on this risk association.

ObjectivesTo evaluate the differences in estimated glomerular filtration rate decline by urinary diversion type (incontinent diversion vs continent diversion) and preoperative estimated glomerular filtration rate among patients undergoing radical cystectomy and urinary diversion.MethodsWe evaluated 1383 patients treated with radical cystectomy between 1980–2006 who had a preoperative estimated glomerular filtration rate of 45‐89 mL/min/1.73 m2. Estimated glomerular filtration rate was estimated using Chronic Kidney Disease Epidemiology Collaboration equations, and patients were stratified by preoperative estimated glomerular filtration rate into chronic kidney disease 2 (estimated glomerular filtration rate 60–89 mL/min/1.73 m2) and chronic kidney disease 3a (estimated glomerular filtration rate 45–59 mL/min/1.73 m2). Multiple definitions of estimated glomerular filtration rate decline were evaluated: (i) 10‐point decline in estimated glomerular filtration rate; (ii) 20% decline in estimated glomerular filtration rate; and (iii) 10% decline in estimated glomerular filtration rate. Time to estimated glomerular filtration rate decline was compared using the Kaplan–Meier method stratified by diversion type. Cox regression models were used to evaluate the association of diversion type with estimated glomerular filtration rate decline risk.ResultsIn total, 74% (1021/1383) of patients underwent incontinent diversion and 26% (362/1383) underwent continent diversion. Preoperative chronic kidney disease 2 and chronic kidney disease 3a were noted among 59% and 41% of patients who underwent incontinent diversion, versus 74% and 26% with continent diversion. Median follow up after RC was 11.2 years. The rate of estimated glomerular filtration rate decline in patients with incontinent diversion versus continent diversion was similar when stratified by preoperative chronic kidney disease 2 and preoperative chronic kidney disease 3a, regardless of estimated glomerular filtration rate decline definition. On multivariable analysis, continent diversion was not associated with estimated glomerular filtration rate decline for patients with preoperative chronic kidney disease 3a.ConclusionsThe risk of estimated glomerular filtration rate decline over 10 years was not significantly different after incontinent diversion versus continent diversion among patients with preoperative chronic kidney disease 2 or chronic kidney disease 3a. Continent diversion does not appear to confer an independently increased risk of estimated glomerular filtration rate decline in patients with preoperative chronic kidney disease 3a.

Objective There is a paucity of data on the impact of complete revascularisation (CR) following percutaneous coronary intervention (PCI) among patients with diabetes with multivessel coronary disease. In this study, we assess the impact of CR, using a relatively simple anatomical definition, on long-term outcomes (median follow-up 7.9 years) in patients with diabetes, and compare with patients without diabetes. Methods 5350 patients with multivessel disease (coronary stenoses ≥70% in ≥2 major epicardial arteries) who underwent PCI between January 1997 and June 2011 were included. Patients were divided into 4 groups according to diabetes and CR status (absence of residual coronary stenosis in major, predominantly proximal, epicardial segments according to Coronary Artery Surgery Study (CASS) classification). Results Patients with diabetes and patients with incomplete revascularisation (IR) had more adverse clinical and angiographic characteristics. IR was frequent in patients with diabetes, and was marginally more common than in patients without diabetes (47% vs 44%, p<0.001). Patients with diabetes and patients without diabetes had higher mortality rates after IR than after CR (HR 1.56 (95% CI (1.39 to 1.85), p<0.001 for patients with diabetes and 1.70 (95% CI (1.50 to 1.92), p<0.001) in patients without diabetes). However, the absolute risk was higher for patients with diabetes (5-year mortality: IR 35.8%, CR 21.2%) than in patients without diabetes (5-year mortality: IR 22.2%, CR 14.1%). In a multivariable model, IR and diabetes mellitus were independent predictors of total mortality. This effect was present in the bare metal stent and drug-eluting stent eras and in patients with stable disease and acute coronary syndromes. Conclusions CR is associated with lower long-term mortality in patients with diabetes and patients without diabetes. However the difference was significantly greater in patients with diabetes compared with patients without diabetes.

AbstractCT and MR have permitted radiology to play a greater, but not definitive, role in detecting the pathologic components of tuberous sclerosis. SEN may be identified in only 80% of patients. Tubers are more ubiquitous and readily identified by MR in children and adults when the brain is myelinated. Since tubers are predominately peripheral hypomyelinated lesions, the detection of small lesions may be delayed until an infant is over 16–18 months of age when the myelin will have extended to the junction between the cortical white and gray matter. SEGA typically evolve later during the first and second decades of life. Successful genetic counseling implies a need to detect tuberous sclerosis at a stage during infancy when imaging may fail to confirm the diagnosis, so tuberous sclerosis remains a clinical diagnosis.