The Contribution of 18F FDG PET-CT for the Investigation of Fever of Unknown Origin and Inflammation of Unknown Origin.

BACKGROUND: Fever of unknown origin and inflammation of unknown origin are highly challenging diagnostic conditions. The current practice for evaluating patients is to conduct a positron emission tomography-computed tomography (PET-CT) scan as either a first- or a second-line modality. We aimed to assess the contributory effect of PET-CT to the diagnosis and compare it with the contributory effect of CT alone. METHODS: We performed a systematic review and meta-analysis. We included all cohorts that examined the contribution of PET-CT to the investigation of classical fever of unknown origin and inflammation of unknown origin. The primary outcome was the contribution of PET-CT to the final diagnosis. Secondary outcomes were sensitivity and specificity of PET-CT and CT scans, and contribution of a CT scan. We pooled the results of all studies and calculated the pooled contributory effect of PET-CT. RESULT: Thirty-six studies (3516 patients) were included in the systematic review. The pooled contribution of PET-CT was 75.4%. The compiled sensitivity and specificity values for all studies were 85.9% and 59.5%, respectively. Five studies (405 patients) compared between the PET-CT component and the total body CT component. The pooled contribution of a CT scan was 68%. The summed sensitivity and specificity values of a CT scan for all studies were 63.1% and 84.4%, respectively. CONCLUSIONS: PET-CT has a contributory effect of 75% for the diagnosis of fever of unknown origin and inflammation of unknown origin. PET-CT had superior sensitivity and inferior specificity vs the CT scan.

Venous thromboembolism prophylaxis in inflammatory bowel disease inpatients - Systematic review and meta-analysis.

INTRODUCTION: Inflammatory bowel disease (IBD) patients are three-times more likely to develop venous thromboembolism (VTE), and guidelines recommend prophylaxis during all hospitalizations. In this systematic review we sought to assess for the benefits and risks of VTE prophylaxis in hospitalized IBD patients. METHODS: We performed a systematic review and meta-analysis. We searched MEDLINE and others up to 2/2022, for studies on IBD inpatients treated with prophylactic anti-coagulation during hospitalization, compared to no prophylaxis. Primary efficacy and safety outcomes were any VTE and major bleeding, respectively. Results were pooled using random-effects models, calculating odds-ratios (OR) and 95% confidence-intervals (CI). The ROBINS-I tool was used to assess bias. RESULTS: We extracted data from 18 observational studies, and two randomized-trial subgroups. The studies were highly variable regarding the included populations, interventions, and outcome definitions. Meta-analysis of all studies showed a non-significant effect of prophylaxis on VTEs (OR 0.97[95%CI 0.49-1.95]). An analysis of eight lower-risk-of-bias studies showed a significant reduction in VTEs (OR 0.27[95%CI 0.13-0.55), number needed to treat(NNT) 34.8[95%CI 26.8-49.8]. A significant protective effect persisted in several subgroups. Major-bleeding was reported in three studies and showed a significant increase with prophylaxis (OR 2.02[95%CI 1.11-3.67], number needed to harm(NNH) 113.6[95%CI 40.7-very-large-number]). CONCLUSIONS: In studies with lower-risk-of-bias, a significant reduction in VTEs was shown in patients treated with VTE prophylaxis (NNT=35), which should be carefully considered against an increased major-bleeding risk (NNH=114). However current data is limited and randomized trials dedicated to IBD inpatients would aid in understating whether universal prophylaxis should be recommended.

Efficacy and safety of rivaroxaban versus apixaban for venous thromboembolism: A systematic review and meta-analysis of observational studies.

BACKGROUND: Direct-acting oral anticoagulants (DOACs) including rivaroxaban and apixaban are preferred over vitamin K antagonists for the treatment of venous thromboembolism (VTE). We conducted a systematic review and a meta-analysis to compare the efficacy and safety of rivaroxaban versus apixaban in the treatment of VTE. METHODS: We conducted an electronic search for studies that directly compared treatment with rivaroxaban and apixaban in adult patients with VTE. The relative risks (RRs) and 95% confidence intervals (CIs) were estimated and pooled using a fixed-effect model unless significant heterogeneity was present (I2 > 40%), then random-effects model was used. The primary efficacy and safety outcomes were recurrent VTE (rVTE) and major bleeding events, respectively. RESULTS: Nine observational studies were included in our meta-analysis, assessing 24,156 patients for apixaban and 38,847 for rivaroxaban. Pooling of data for our primary efficacy outcome showed a trend towards lower risk of rVTE with apixaban compared to rivaroxaban (RR 0.77, 95% CI 0.57-1.04, I2 = 53%). Analysis of our primary safety outcome showed a significantly lower risk of major bleeding with apixaban compared to rivaroxaban (RR 0.68, 95% CI 0.61-0.76, I2 = 0%). Apixaban was associated with significantly decreased risk of net clinical harm, clinically relevant non major bleeding (CRNMB) and any bleeding, compared to rivaroxaban (RR 0.75, 95% CI 0.61-0.92, I2 = 50%; RR 0.58, 95% CI 0.50-0.67, I2 = 7%; RR 0.64, 95% CI 0.59-0.70, I2 = 0%, respectively). CONCLUSIONS: Apixaban is associated with a significantly lower risk of major bleeding compared to rivaroxaban for treatment of VTE. Given the limitations of the existing evidence, further interventional studies comparing the two drugs are needed.

A Systematic Review Assessing the Underrepresentation of Cancer Patients in COVID-19 Trials.

BACKGROUND: The new severe acute respiratory syndrome coronavirus 2 has emerged as a global pandemic that threatens thousands around the world. Observational cohort studies have demonstrated that cancer patients have inferior outcomes due to underlying malignancy, treatment-related immunosuppression, or increased comorbidities. We aimed to examine the representation of cancer patients (hematological malignancies and solid tumors) in COVID-19 therapeutic and prophylactic interventional trials. METHODS: In this review, all randomized controlled trials (RCTs) published between December 2019 and August 2021 were included. We included only trials evaluating medications that were recommended by NIH guidelines: steroids, tocilizumab, remdesivir, and REGN-COV2. RESULTS: The search yielded 541 potentially relevant RCTs, 22 of which were considered suitable. All trials included patients with solid cancer and hematological malignancies in the formal reported inclusion criteria. However, only two trials reported the accurate number of cancer patients included. Ten trials excluded neutropenic patients and seven trials excluded thrombocytopenic patients. Eleven trials excluded patients that were treated with any immunosuppression treatment. None of the two trials that included cancer patients reported separate outcomes for this population. CONCLUSION: Our systematic review shows that cancer patients are underrepresented in COVID-19 interventional therapeutic trials, and evidence regarding outcomes are lacking.

Evaluating outcomes of adult patients with acute lymphoblastic leukemia and lymphoblastic lymphoma treated on the GMALL 07/2003 protocol.

Chemotherapy-based approaches still constitute an essential feature in the treatment paradigm of adult acute lymphoblastic leukemia (ALL). The German Multicenter Study Group (GMALL) is a well-established protocol for ALL. In this study, we assessed our recent experience with the GMALL 07/2003 protocol reviewing all adult ALL patients who were treated with GMALL in three major centers in Israel during 2007-2020. The analysis comprised 127 patients with a median age of 41 years (range 17-83). Sixty-two were B-ALL (49%), 20 (16%) patients were Philadelphia chromosome positive ALL, and 45 (35%) were T-ALL. The 2-year and 5-year overall survival rates were 71% and 57%, respectively. The 2-year relapse rate was 30% with 2-year and 5-year leukemia-free survival rates of 59% and 50%, respectively. Adolescents and young adults experienced significantly longer overall survival (84 months versus 51 months; p=0.047) as well as leukemia-free survival compared with older patients (66 months versus 54 months, p=0.003; hazard ratio=0.39, 95% confidence interval, 0.19-0.79; p=0.009). T-ALL patients had longer survival compared to B-ALL patients while survival was comparable among Philadelphia chromosome positive patients and Philadelphia chromosome negative patients. An increased number of cytogenetic clones at diagnosis were tightly associated with adverse prognosis (15-month survival for ≥2 clones versus 81 months for normal karyotype; p=0.003). Positive measurable residual disease studies following consolidation were predictive for increased risk of relapse (64% versus 22%; p=0.003) and shorter leukemia-free survival (11 months versus 42 months; p=0.0003). While GMALL is an effective adult regimen, a substantial patient segment still experiences relapse.