V/Q SPECT and computed tomographic pulmonary angiography.

Planar ventilation and perfusion (V/Q) scintigraphy has been largely displaced by computed tomography pulmonary angiography (CTPA) in recent years for the diagnosis of pulmonary embolism (PE). This change can be attributed to multiple studies that demonstrate CTPA has a reasonable sensitivity and good prognostic value in negative cases, associated with the ability to deliver few indeterminate results and provide an alternate diagnosis in a significant number of patients. However, the technique has significant limitations. The Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) study has shown a sensitivity of 83%, which is not optimal. However, CT technology has greatly progressed since this time, and therefore it is likely that this number has improved. The PIOPED II study has also shown that there may be a problem in positive or negative predictive value when the imaging results are discordant with the clinical probability. Additional concerns include allergies, contrast nephropathy associated with the use of intravenous contrast in patients with impaired creatinine clearance, suboptimal results in pregnant women, and high radiation exposure. In recent years, V/Q single-photon emission computed tomography has emerged as a mature technique for the diagnosis of PE and has been shown to be clearly superior to planar V/Q. The technique has excellent sensitivity for PE and is not associated with most of the limitations of CTPA, although it has its own set of limitations in patients with very severe chronic obstructive pulmonary disease or with a severely abnormal chest x-ray. V/Q single-photon emission computed tomography can be used as the initial modality for PE diagnosis in a wide variety of situations although CTPA remains invaluable in specific scenarios.

Prospective evaluation of the negative predictive value of V/Q SPECT using 99mTc-Technegas.

OBJECTIVE: To verify the negative predictive value of pulmonary ventilation/perfusion scintigraphy with single photon emission computed tomography (V/Q SPECT) in ruling out pulmonary thromboembolism. METHODS: V/Q SPECT using 99mTc-Technegas was performed on 584 patients to rule out pulmonary thromboembolism between October 2004 and July 2005. Pulmonary thromboembolism was defined as any clear-cut vascular mismatch, regardless of size. Indeterminate scans were defined as cases having matching vascular type defects with a corresponding X-ray abnormality, or cases with equivocal mismatches. Other patterns were considered negative for pulmonary thromboembolism. Outcome data was gathered >3 months after the scan. Absence of pulmonary thromboembolism was defined as any patient still alive at least 3 months after the scan, with no anticoagulation treatment and no proof of pulmonary thromboembolism by other techniques, either at the time of the scan or during follow-up, or death by other causes. RESULTS: One hundred and eight patients (19%) had a positive pulmonary thromboembolism reading, 18 (3%) an indeterminate study, and 458 (78%) patients had a negative reading for pulmonary thromboembolism. There were 189 patients with an abnormal chest X-ray. The mean follow-up time was 165 days. Of the 458 patients classified as negative for pulmonary thromboembolism, patients receiving chronic anticoagulation for other causes were excluded from follow-up (n=53), which left 405 patients for final analysis. There were no pulmonary thromboembolism-related deaths in the negative group. Six patients were identified as false negatives. The negative predictive value is estimated at 98.5%. CONCLUSION: SPECT pulmonary scintigraphy using 99mTc-Technegas demonstrates a high negative predictive value and a low indeterminate rate.

Optimization of whole-body positron emission tomography imaging by using delayed 2-deoxy-2-[F-18]fluoro-D: -glucose Injection following I.V. Insulin in diabetic patients.

PURPOSE: High blood glucose levels may decrease the sensitivity of 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG)-positron emission tomography (PET). The goal of this study was to assess whether intravenous (i.v.) insulin followed by FDG injection 60 minutes later could decrease the blood glucose level of hyperglycemic patients without altering muscular, liver, or lung FDG uptake. METHODS: We evaluated 53 diabetic patients with a fasting glycemia higher than 7.0 mmol/l. The control group consisted of 53 nondiabetic patients with a normal fasting glycemia. Sixty minutes before FDG injection, all diabetic patients received up to two intravenous bolus of insulin. Regions of interest were drawn over the lungs, heart, liver, skeletal muscles, and over the most active lung nodule, if present, to calculate a standardized uptake value (SUV) normalized to the lean body weight. RESULTS: After one or two boluses of insulin (mean 3.4 units), 39 diabetic patients decreased their blood glucose level from 9.4 +/- 1.8 to 6.1 +/- 1.3 mmol/l. In 14 patients, two doses of insulin (mean 4.5 +/- 2.3 units) were not sufficient, but managed to decrease the blood glucose level from 10.6 +/- 2.1 to 9.1 +/- 2.1 mmol/l. There was no significant difference for the SUV calculated on the lung, liver, heart, and skeletal muscles. No differences were noted in lung tumor uptake in patients who received insulin compared to the control group. CONCLUSIONS: With a sufficient waiting period between the insulin and FDG injections, an i.v. bolus of insulin makes it possible to effectively decrease glycemia of diabetic patients without increasing muscular FDG uptake.

Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec.

BACKGROUND: Since 2002, an epidemic of Clostridium difficile-associated-diarrhea (CDAD) associated with a high case-fatality rate has involved >30 hospitals in the province of Quebec, Canada. In 2003, a total of 55% of patients with CDAD at our hospital had received fluoroquinolones in the preceding 2 months. It has been suggested that massive use of proton pump inhibitors might have facilitated this epidemic. METHODS: To delineate the risk of CDAD associated with specific classes of antibiotics and whether this is modulated by concomitant use of proton pump inhibitors and other drugs altering gastric acidity or gastrointestinal motility, we conducted a retrospective cohort study of patients hospitalized in a teaching hospital in Sherbrooke, Canada, during the period of January 2003 through June 2004. We obtained data on 7421 episodes of care corresponding to 5619 individuals. Patients were observed until they either developed CDAD or died or for 60 days after discharge from the hospital. Adjusted hazard ratios (AHRs) were calculated using Cox regression. RESULTS: CDAD occurred in 293 patients. Fluoroquinolones were the antibiotics most strongly associated with CDAD (AHR, 3.44; 95% confidence interval [CI], 2.65-4.47). Almost one-fourth of all inpatients received quinolones, for which the population-attributable fraction of CDAD was 35.9%. All 3 generations of cephalosporins, macrolides, clindamycin, and intravenous beta-lactam/beta-lactamase inhibitors were intermediate-risk antibiotics, with similar AHRs (1.56-1.89). Proton pump inhibitors (AHR, 1.00, 95% CI, 0.79-1.28) were not associated with CDAD. CONCLUSIONS: Administration of fluoroquinolones emerged as the most important risk factor for CDAD in Quebec during an epidemic caused by a hypervirulent strain of C. difficile.

Severe and resistant hypoglycemia associated with concomitant gatifloxacin and glyburide therapy.

Severe and resistant hypoglycemia occurred in two patients with diabetes mellitus who were receiving concomitant gatifloxacin and glyburide. An 84-year-old woman treated with glyburide for type 2 diabetes mellitus experienced, for the first time, a severe episode of hypoglycemia after 2 days of gatifloxacin 400 mg/day for nonproductive cough. Her blood glucose level on hospital admission was 28 mg/dl. Gatifloxacin and glyburide were discontinued, and the patient was treated with intravenous dextrose infused over 36 hours. Glyburide was restarted before her discharge, with no recurrence of hypoglycemia. A 79-year-old man with type 2 diabetes mellitus treated with glyburide was prescribed gatifloxacin 400 mg/day for pneumonia. After 1 day of therapy, the patient was admitted to the emergency department in a coma. His blood glucose level was 18 mg/dl. Despite discontinuation of gatifloxacin and oral hypoglycemic therapy, hypoglycemia was reversed only after administration of multiple boluses of intravenous dextrose, followed by intravenous dextrose infused over 48 hours. On hospital day 7, gliclazide and levofloxacin were started; the patient experienced no recurrence of hypoglycemia and was discharged on day 10. Several cases of severe and resistant hypoglycemia associated with gatifloxacin therapy have been reported in the recent literature. Although the exact mechanism is not fully understood, it may be linked to a gatifloxacin-induced closing of the adenosine 5'-triphosphate-sensitive potassium channels in the pancreatic beta cells, leading to insulin secretion. The onset of hypoglycemia in relation to the start of gatifloxacin suggests that the drug precipitated this adverse event. Patients receiving oral hypoglycemic agents are at greater risk of experiencing gatifloxacin-induced hypoglycemia than patients not receiving these agents. Clinicians should be aware of this potentially life-threatening adverse event and monitor blood glucose levels in all patients receiving concomitant oral hypoglycemic agents and gatifloxacin.

The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma.

BACKGROUND: The survival of patients with diffuse large-B-cell lymphoma after chemotherapy is influenced by molecular features of the tumors. We used the gene-expression profiles of these lymphomas to develop a molecular predictor of survival. METHODS: Biopsy samples of diffuse large-B-cell lymphoma from 240 patients were examined for gene expression with the use of DNA microarrays and analyzed for genomic abnormalities. Subgroups with distinctive gene-expression profiles were defined on the basis of hierarchical clustering. A molecular predictor of risk was constructed with the use of genes with expression patterns that were associated with survival in a preliminary group of 160 patients and was then tested in a validation group of 80 patients. The accuracy of this predictor was compared with that of the international prognostic index. RESULTS: Three gene-expression subgroups--germinal-center B-cell-like, activated B-cell-like, and type 3 diffuse large-B-cell lymphoma--were identified. Two common oncogenic events in diffuse large-B-cell lymphoma, bcl-2 translocation and c-rel amplification, were detected only in the germinal-center B-cell-like subgroup. Patients in this subgroup had the highest five-year survival rate. To identify other molecular determinants of outcome, we searched for individual genes with expression patterns that correlated with survival in the preliminary group of patients. Most of these genes fell within four gene-expression signatures characteristic of germinal-center B cells, proliferating cells, reactive stromal and immune cells in the lymph node, or major-histocompatibility-complex class II complex. We used 17 genes to construct a predictor of overall survival after chemotherapy. This gene-based predictor and the international prognostic index were independent prognostic indicators. CONCLUSIONS: DNA microarrays can be used to formulate a molecular predictor of survival after chemotherapy for diffuse large-B-cell lymphoma.