Bevacizumab-Associated Thrombotic Microangiopathy Treated with Eculizumab: A Case Report.

BACKGROUND Bevacizumab is an approved targeted therapy for metastatic cancer treatment. It can have adverse effects on multiple organs. Despite its low incidence, thrombotic microangiopathy (TMA) is the most severe complication. TMA has been associated with complement dysregulation, and treatment with eculizumab can be effective, despite the paucity of literature on eculizumab therapy for bevacizumab-associated TMA. To date, 10 cases have been reported, with less than half of them including a kidney biopsy. We present a new case of bevacizumab-associated TMA successfully treated with eculizumab, along with kidney biopsy records and an overview of mechanisms underlying TMA development in bevacizumab-treated patients. CASE REPORT A female patient diagnosed with metastatic breast cancer who was treated with bevacizumab in conjunction with chemotherapy was admitted to the hospital for acute kidney injury requiring hemodialysis, microangiopathic hemolytic anemia, and thrombocytopenia. TMA was diagnosed and was later confirmed by a kidney biopsy. Primary causes for TMA, such as ADAMTS13 deficiency and shiga toxin associated hemolytic-uremic syndrome, were ruled out, and the patient's condition was ultimately found to be triggered by exposure to bevacizumab. After discontinuing bevacizumab and receiving 4 weekly doses of eculizumab, kidney function and hematological parameters improved. CONCLUSIONS Bevacizumab-associated TMA can be reversed or attenuated in some patients with the use of eculizumab (inhibiting complement system overactivation), possibly reducing time to recovery, with fewer long-term sequelae. This additional case encourages future clinical trials to evaluate the safety and efficacy of eculizumab in cases of TMA associated with bevacizumab.

Fatty acid synthesis in Xylella fastidiosa: correlations between genome studies, 13C NMR data, and molecular models.

Xylella fastidiosa was the first plant pathogen to have its complete genome sequence elucidated. Routine database analyses suggested that two enzymes essential for fatty acid synthesis were missing, one of these is the holo-acyl-carrier-protein synthase. However, here we demonstrate, using (13)C NMR spectroscopy, that X. fastidiosa is indeed able to synthesize fatty acids from acetate via an apparently conventional metabolic pathway. We further identify a gene product HetI, an alternative phosphopantetheinyl transferase, which we propose to fill the missing link. Homology modeling of HetI shows conservation of the Coenzyme A binding site suggesting it to be an active enzyme and reveals several interesting structural features when compared with the surfactin synthase-activating enzyme, on which the model was built. These include a simplified topology due to N- and C-terminal deletions and the observation of a novel serine ladder.