Prostate tumors are among the most heterogeneous of cancers, both histologically and clinically. Microarray expression analysis was used to determine whether global biological differences underlie common pathological features of prostate cancer and to identify genes that might anticipate the clinical behavior of this disease. While no expression correlates of age, serum prostate specific antigen (PSA), and measures of local invasion were found, a set of genes was identified that strongly correlated with the state of tumor differentiation as measured by Gleason score. Moreover, a model using gene expression data alone accurately predicted patient outcome following prostatectomy. These results support the notion that the clinical behavior of prostate cancer is linked to underlying gene expression differences that are detectable at the time of diagnosis.
Objective To derive and validate an objective clinical prediction rule for the presence of uncomplicated ureteral stones in patients eligible for computed tomography (CT). We hypothesized that patients with a high probability of ureteral stones would have a low probability of acutely important alternative findings.Design Retrospective observational derivation cohort; prospective observational validation cohort.Setting Urban tertiary care emergency department and suburban freestanding community emergency department.Participants Adults undergoing non-contrast CT for suspected uncomplicated kidney stone. The derivation cohort comprised a random selection of patients undergoing CT between April 2005 and November 2010 (1040 patients); the validation cohort included consecutive prospectively enrolled patients from May 2011 to January 2013 (491 patients). Main outcome measuresIn the derivation phase a priori factors potentially related to symptomatic ureteral stone were derived from the medical record blinded to the dictated CT report, which was separately categorized by diagnosis. Multivariate logistic regression was used to determine the top five factors associated with ureteral stone and these were assigned integer points to create a scoring system that was stratified into low, moderate, and high probability of ureteral stone. In the prospective phase this score was observationally derived blinded to CT results and compared with the prevalence of ureteral stone and important alternative causes of symptoms. ResultsThe derivation sample included 1040 records, with five factors found to be most predictive of ureteral stone: male sex, short duration of pain, non-black race, presence of nausea or vomiting, and microscopic hematuria, yielding a score of 0-13 (the STONE score). Prospective validation was performed on 491 participants. In the derivation and validation cohorts ureteral stone was present in, respectively, 8.3% and 9.2% of the low probability (score 0-5) group, 51.6% and 51.3% of the moderate probability (score 6-9) group, and 89.6% and 88.6% of the high probability (score 10-13) group. In the high score group, acutely important alternative findings were present in 0.3% of the derivation cohort and 1.6% of the validation cohort. ConclusionsThe STONE score reliably predicts the presence of uncomplicated ureteral stone and lower likelihood of acutely important alternative findings. Incorporation in future investigations may help to limit exposure to radiation and over-utilization of imaging.Trial registrationwww.clinicaltrials.gov NCT01352676.
Higher rates of glucose usage generally correlate with poor prognosis in several types of malignant tumours. Experimental studies (both in vitro and in vivo) have shown that 2-deoxy-D-glucose (2-DG), a glucose analog and glycolytic inhibitor, enhances radiation-induced damage selectively in tumor cells while protecting normal cells, thereby suggesting that 2-DG can be used as a differential radiomodifier to improve the efficacy of radiotherapy. Clinical trials undertaken to study the feasibility, safety, and validity of this suggested approach will be described. Based on 2-DG-induced radiosensitization observed in primary organ cultures of cerebral glioma tissues, clinical trials were designed taking into consideration the radiobiology of gliomas and pharmacokinetics of 2-DG. Phase I/II clinical trials have unequivocally demonstrated that a combination of 2-DG (200-300 mg 2-DG per kg body weight orally administered after overnight fasting, 20 min before irradiation) with large weekly fractions (5 Gy/fraction) of low-LET radiotherapy is well tolerated without any acute toxicity or late radiation damage to the normal brain tissue. Nonserious transient side effects similar to hypoglycemia induced disturbances like restlessness, nausea, and vomiting were observed at the 2-DG doses used. Data from these trials involving more than 100 patients have clearly indicated a moderate increase in the survival, with a significant improvement in the quality of life with clinicopathological evidence of protection of normal brain tissue. A phase III multicentric trial to evaluate the efficacy of the combined treatment is in progress. Directions for future studies are discussed.
Oral administration of 2-DG combined with large fractions of radiation (5 Gy/fraction/week) is safe and could be tolerated in glioblastoma patients without any acute toxicity and late radiation damage to the normal brain. Further clinical studies to evaluate the efficacy of the combined treatment are warranted.
Study objective-We determine whether renal point-of-care limited ultrasonography (PLUS) used in conjunction with the Sex, Timing, Origin, Nausea, Erythrocytes (STONE) clinical prediction score can aid identification of emergency department (ED) patients with uncomplicated ureteral stone or need for urologic intervention.Methods-This was a prospective observational study of adult ED patients undergoing computed tomography (CT) scan for suspected ureteral stone. The previously validated STONE score classifies patients into risk categories of low (≈10%), moderate (≈50%), or high (≈90%) for symptomatic stone. Renal PLUS assessed for presence of hydronephrosis before CT scanning. The primary outcomes of symptomatic ureteral stone or acutely important alternative finding were abstracted from CT reports. The secondary outcome, urologic intervention, was assessed by 90-day follow-up interview and record review.Results-Of 835 enrolled patients, ureteral stone was identified in 53%, whereas 6.5% had an acutely important alternative finding on CT. Renal PLUS modestly increased sensitivity for symptomatic stone among low and moderate STONE score categories. Moderate or greater hydronephrosis improved specificity from 67% (62% to 72%) to 98% (93% to 99%) and 42% (37% to 47%) to 92% (86% to 95%) in low-and moderate-risk patients, with likelihood ratios of 22 (95% CI, 4.2-111) and 4.9 (95% CI, 2.9-8.3), respectively. Test characteristics among high-risk patients were unchanged by renal PLUS. For urologic intervention, any hydronephrosis was 66% sensitive (57% to 74%), whereas moderate or greater hydronephrosis was 86% specific overall * Corresponding Author. brockdaniels@gmail.com. Author contributions: BD and CLM conceived the study. CPG, DS, and CLM and obtained research funding. SL and CLM supervised the conduct of the trial and data collection. SL participated in recruitment of patients. AM, SL, RJ, and CLM managed the data, including quality control. CPG and AM provided statistical advice. CPG, AM, and DS provided advisement on study design and methodology. BD, AM, RJ, and CLM analyzed the data. BD drafted the article and all authors contributed substantially to its revision. BD takes responsibility for the paper as a whole.Presented as an abstract at the Society for Academic Emergency Medicine annual meeting, May 2014, Dallas, TX.Clinical trial registration number: NCT01352676 HHS Public Access
Renal artery pseudoaneurysm is an uncommon complication following laparoscopic partial nephrectomy. These patients often present in delayed fashion. Selective angiographic embolization is the initial treatment of choice.
F-18 FDOPA scan is superior to both F-18 FLT and F-18 FDG for visualization of primary and recurrent low grade gliomas. F-18-FLT should not be considered for evaluation of recurrent low grade gliomas.
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