Eculizumab in Shiga toxin-producing Escherichia coli hemolytic uremic syndrome: a systematic review.

BACKGROUND: Infection-associated hemolytic uremic syndrome (IA-HUS), most often due to infection with Shiga toxin-producing bacteria, mainly affects young children. It can be acutely life-threatening, as well as cause long-term kidney and neurological morbidity. Specific treatment with proven efficacy is lacking. Since activation of the alternative complement pathway occurs in HUS, the monoclonal C5 antibody eculizumab is often used off-label once complications, e.g., seizures, occur. Eculizumab is prohibitively expensive and carries risk of infection. Its utility in IA-HUS has not been systematically studied. This systematic review aims to present, summarize, and evaluate all currently available data regarding the effect of eculizumab administration on medium- to long-term outcomes (i.e., outcomes after the acute phase, with a permanent character) in IA-HUS. METHODS: PubMed, Embase, and Web of Science were systematically searched for studies reporting the impact of eculizumab on medium- to long-term outcomes in IA-HUS. The final search occurred on March 2, 2022. Studies providing original data regarding medium- to long-term outcomes in at least 5 patients with IA-HUS, treated with at least one dose of eculizumab during the acute illness, were included. No other restrictions were imposed regarding patient population. Studies were excluded if data overlapped substantially with other studies, or if outcomes of IA-HUS patients were not reported separately. Study quality was assessed using the ROBINS-I tool for risk of bias in non-randomized studies of interventions. Data were analyzed descriptively. RESULTS: A total of 2944 studies were identified. Of these, 14 studies including 386 eculizumab-treated patients met inclusion criteria. All studies were observational. Shiga toxin-producing E. coli (STEC) was identified as the infectious agent in 381 of 386 patients (98.7%), effectively limiting the interpretation of the data to STEC-HUS patients. Pooling of data across studies was not possible. No study reported a statistically significant positive effect of eculizumab on any medium- to long-term outcome. Most studies were, however, subject to critical risk of bias due to confounding, as more severely ill patients received eculizumab. Three studies attempted to control for confounding through patient matching, although residual bias persisted due to matching limitations. DISCUSSION: Current observational evidence does not permit any conclusion regarding the impact of eculizumab in IA-HUS given critical risk of bias. Results of randomized clinical trials are eagerly awaited, as new therapeutic strategies are urgently needed to prevent long-term morbidity in these severely ill patients. SYSTEMATIC REVIEW REGISTRATION NUMBER: OSF Registries, MSZY4, Registration DOI https://doi.org/10.17605/OSF.IO/MSZY4 .

Diagnostic Accuracy of PET Tracers for the Differentiation of Tumor Progression from Treatment-Related Changes in High-Grade Glioma: A Systematic Review and Metaanalysis.

Posttreatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent Response Assessment in Neuro-Oncology recommendations, PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and metaanalysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: PubMed, Web of Science, and Embase were searched systematically. Study selection, data extraction, and quality assessment were performed independently by 2 authors. Metaanalysis was performed using a bivariate random-effects model when at least 5 studies were included. Results: The systematic review included 39 studies (11 tracers). 18F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95% confidence interval, 72%-92%) and 84% (95% confidence interval, 69%-93%), respectively. O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) (7 studies, 172 lesions) demonstrated a sensitivity of 90% (95% confidence interval, 81%-95%) and specificity of 85% (95% confidence interval, 71%-93%). For S-11C-methyl)-l-methionine (11C-MET) (8 studies, 151 lesions), sensitivity was 93% (95% confidence interval, 80%-98%) and specificity was 82% (95% confidence interval, 68%-91%). The numbers of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93%-100% and 0%-100%, respectively, for 18F-FLT; 85%-100% and 72%-100%, respectively, for 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine (18F-FDOPA); and 100% and 70%-88%, respectively, for 11C-choline. Conclusion:18F-FET and 11C-MET, both amino-acid tracers, showed a comparably higher sensitivity than 18F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited; thus, 18F-FET and 11C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas.