FDG PET is a robust tool for the diagnosis of spondylodiscitis: a meta-analysis of diagnostic data.

PURPOSE: Spondylodiscitis is a rare infectious entity that requires multimodal diagnostic procedures. We evaluated the diagnostic performance of 18F-FDG PET on suspected spondylodiscitis based on published literature. PATIENTS AND METHODS: We searched the PubMed and EMBASE for pertinent studies up to July 2013. We implemented a patient-based meta-analysis of diagnostic data for FDG PET (the index test) against clinical, laboratory, and/or radiologic evidence of disease (the reference standard). A bivariate analysis was implemented to account for variability beyond the threshold effect. The individual patient data analysis was used to assess confounding factors that moderate diagnostic performance. RESULTS: Twelve studies provided the diagnostic data on FDG PET and spondylodiscitis, comprising 224 patients. The combined sensitivity across studies was 0.97 [95% confidence interval (CI), 0.83-1.00], the specificity was 0.88 (95% CI, 0.74-0.95), and the area under the curve was 0.98 (95% CI, 0.96-0.99). For prior probabilities greater than 0.50, the corresponding positive predictive value was 0.96 (0.93-0.98), and the negative predictive value was 0.85 (0.82-0.88). In the individual patient data analysis, metallic implants, dual PET/CT scanners and the addition of other imaging modalities to confirm disease were significant outcome moderators; only PET/CT remained significant in the adjusted analysis. PET/CT scanners improved the diagnostic performance, as opposed to the clinical data (age, sex, lesion site), which did not alter outcome. CONCLUSIONS: FDG PET is a robust diagnostic test when spondylodiscitis is suspected and is excellent for exclusion of infectious spondylodiscitis given its low likelihood ratio negative (<0.1). Importantly, this diagnostic test is unaffected by other confounders, including the presence of implants, when PET/CT is used.

Interleukin-6 polymorphisms and hematologic malignancy: a re-appraisal of evidence from genetic association studies.

CONTEXT: Interleukin-6 (IL-6) is implicated in the pathophysiology of hematologic neoplasia. OBJECTIVE: To review the role of IL-6 single nucleotide polymorphisms (SNPs) in hematologic neoplasia. METHODS: PubMed and EMBASE search of genetic association studies. Effects were summarized using the model-free generalized odds ratio (ORG), and the mode of inheritance was estimated for significant associations. RESULTS: Seventeen articles provided data on 20 distinct SNPs. The IL-6 receptor rs8192284 was associated with an increased risk of hematologic malignancy (combined ORG 1.42, 95%CI 1.03-1.96), including multiple myeloma (ORG 1.39, 95%CI 0.99-1.95). The IL-6 promoter rs1800795 conferred protection against young adult Hodgkin's disease (ORG 0.68, 95%CI 0.48-0.95). Significant single-study effects for four other SNPs-disease associations were estimated. The IL-6 promoter rs1800795 and rs1800797 were not associated with overall susceptibility to non-Hodgkin's lymphomas. CONCLUSIONS: There is accumulating evidence that the IL-6 promoter, receptor and signal transducer SNPs can modify disease susceptibility.

Effect of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in lymphoma: a meta-analysis of published clinical trials and a decision tree addressing prolonged prophylaxis and maintenance.

Lamivudine prophylaxis is an effective strategy in HbSAg-positive patients receiving cancer chemotherapy. Recent data indicate that a lamividune-prophylaxis strategy results in a decrease of hepatitis B virus (HBV) reactivation rates, though its effect on HBV-mortality remains equivocal. This report evaluates the benefits from this strategy among lymphoma patients and develops a management approach for patients with prolonged immunosuppression. A Medline search was conducted to retrieve published trials on HBsAg-positive lymphoma patients receiving prophylactic lamivudine during chemotherapy. Basic inclusion criterion was to report HBV-reactivation rates with and without lamivudine prophylaxis. A meta-analysis of the risk of HBV-reactivation and HBV-related mortality was conducted, and the pooled effect was calculated as risk ratio (RR). We found that lamivudine prophylaxis is associated with a significant reduction in hepatitis B virus reactivation (RR 0.21, 95%CI 0.13-0.35) and a trend in reducing HBV-related mortality (RR 0.68, 95%CI 0.19-2.49). In order to study the long-term effects of anti-HBV prophylaxis when prolonged immunosuppression is needed, we used our findings to model a decision tree. Overall survival was the main outcome used in the analysis. Rituximab maintenance in B-cell lymphomas was used as a paradigm of prolonged immunosuppression. We found that extended anti-HBV prophylaxis can improve survival rates by 2.4% in HBsAg-positive patients. If 1,000 HBsAg-positive lymphoma patients receive prophylaxis, one will die from hepatitis B virus reactivation versus 25/1,000 if no prophylaxis is administered. This effect is probably mediated through a reduction of hepatitis B virus reactivation and HBV-related mortality. The ideal antiviral agent needs to be determined.

Prognostic importance of increased plasma amino-terminal pro-brain natriuretic peptide levels in a large noncardiac, general intensive care unit population.

The present study aimed to determine whether amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) predicts intensive care unit (ICU) mortality in a cohort of general, noncardiac, critically ill patients. To this end, a total of 233 consecutive mechanically ventilated patients (109 men) having a median age of 60 years and a wide range in admitting diagnoses, including medical (n = 118), surgical (n = 83), and multiple trauma (n = 32) cases were prospectively studied. Median Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment scores on ICU admission were 16 and 9, respectively. The study end point was ICU outcome. Blood samples were drawn on admission in the ICU and on postadmission days 1 and 2 to determine NT-pro-BNP levels. In a subgroup (n = 77), admission proinflammatory and anti-inflammatory cytokine levels, including TNF-alpha, IL-6, and IL-10, were also measured. Nonsurvivors (n = 98) had significantly higher NT-pro-BNP levels than survivors (n = 135) on admission in the ICU (2,074 vs. 283 pg/mL; P < 0.001), on day 1 (2,197 vs. 221 pg/mL; P < 0.001), and on day 2 (2,726 vs. 139 pg/mL; P < 0.001). Median values for TNF-alpha, IL-6, and IL-10 were 3.70, 131.57, and 111.88 pg/mL, respectively. Receiver operating characteristic analysis showed that the area under the receiver operating characteristic curve in predicting ICU mortality was 0.70 for APACHE II and 0.77 for admission NT-pro-BNP (P = 0.08). The cutoff in admission NT-pro-BNP that best predicted outcome was 941 pg/mL. Multiple logistic regression analysis revealed that APACHE II score (odds ratio, 1.06; P = 0.007) and the best cutoff point in admission NT-pro-BNP (odds ratio, 7.74; P < 0.001) independently predicted ICU mortality, even if cytokines were entered in the analysis. In conclusion, plasma NT-pro-BNP is frequently raised in noncardiac, mixed, critically ill patients, and nonsurvivors have consistently higher levels than survivors. Elevated admission NT-pro-BNP represents an independent predictor for poor ICU outcome in the presence of clinical severity scores.