Bruce Feinberg

Eculizumab fails to inhibit generation of C5a in vivo

To the editor:nnEculizumab is a monoclonal antibody (mAb) reputed to block C5 by preventing enzymatic generation of active components C5a and C5b.[1][1] C5a is a proinflammatory mediator whereas C5b combines with C6, C7, C8, and C9 to form the membrane attack complex C5b-9, which contributes to

Impact of initiating antiemetic prophylaxis with palonosetron versus ondansetron on risk of uncontrolled chemotherapy-induced nausea and vomiting in patients with lung cancer receiving multi-day chemotherapy

PurposeThe purpose of this study is to examine the risk of uncontrolled chemotherapy-induced nausea/vomiting (CINV) among lung cancer patients receiving multi-day chemotherapy and ondansetron- or palonosetron-initiated prophylactic antiemetic regimens in a community oncology setting.MethodsThe Georgia Cancer Specialists electronic medical records database was used to retrospectively identify lung cancer patients who received multi-day cisplatin or carboplatin regimens with ondansetron or palonosetron on dayxa01 between April 1, 2006 and July 31, 2009. Uncontrolled CINV events were identified through ICD-9-CM codes (nausea/vomiting), CPT codes (dehydration), rescue medications, nausea/vomiting hospitalizations, and/or antiemetic therapy after last chemotherapy administration of the cycle. Risk for uncontrolled CINV, up to 7xa0days after last chemotherapy administration, was analyzed at cycle level using logistic regression with regressors of gender, age, number of chemotherapy administration days, Charlson comorbidity index, cancer type, multicancer diagnoses, and chemotherapy regimen.ResultsA total of 209 palonosetron and 153 ondansetron patients (702 and 515 cycles, respectively) met the inclusion criteria. Palonosetron patients were significantly older (mean 67.9 versus 63.9xa0years; Pu2009<u20090.0001), with no significant difference in gender, baseline comorbidity score, or multicancer diagnosis. Palonosetron cycles had 63% lower risk for uncontrolled CINV events versus ondansetron cycles [odds ratio (OR) 0.37; 95% confidence interval (CI) 0.25–0.54; Pu2009<u20090.0001]. Sub-analysis by chemotherapy supported overall analysis (cisplatin OR 0.09; 95% CI 0.04–0.25; Pu2009<u20090.0001; carboplatin OR 0.46; 95% CI 0.30–0.70; Pu2009=u20090.0003).ConclusionIn this retrospective analysis of lung cancer patients, multi-day chemotherapy cycles administered with palonosetron on dayxa01 were associated with a significantly lower risk for uncontrolled CINV events versus ondansetron-initiated chemotherapy cycles.

Maternal and feto-placental phenotypes of early-onset severe preeclampsia.

Abstract Objective: To characterize maternal and feto-placental phenotypes of severe preeclampsia that trigger early-onset delivery. Methods: A retrospective cohort review of pregnant women receiving care from 2000 to 2010. Subjects with early-onset severe preeclampsia delivering between 20 and 32 weeks were identified excluding multiple gestations or major anomalies. We defined indications for delivery as maternal (i.e. severe headache or abnormal laboratory parameters), feto-placental (i.e. non-reassuring tracing) or mixed (i.e. both maternal and feto-placental factors). To characterize the groups, demographic, clinical, laboratory, ultrasound and pathology data were abstracted. Statistical analysis was conducted. Results: We identified 164 subjects meeting inclusion criteria. Indications for delivery were maternal (57.3%), feto-placental (29.9%) or mixed (12.8%). Compared to neonates delivered for maternal indications, birthweight was significantly lower among neonates delivered for feto-placental or mixed indications (pu2009<u20090.001). While placental findings were largely similar between groups, abnormal cord insertion was more common in subjects delivered for feto-placental factors (pu2009=u20090.02). Women delivered for maternal indications had more significant lab abnormalities than women delivered for feto-placental or mixed indications. Conclusion: In attempting to classify early-onset severe preeclampsia by delivery indication, we found patterns to suggest that feto-placental and maternal phenotypes of disease may have distinct pathophysiologic underpinnings.

Response: Maternal and cord C5a in response to eculizumab

We appreciate the interest of Volokhina al[1][1] in our recent letter to the editor in Blood .[2][2] Their data on measurement of C5a in human plasma in response to eculizumab adds to the scant literature on this topic. They raise 2 criticisms that we did not address in our original letter: (1)

Are We Getting Closer to Explaining Preeclampsia

Preeclampsia continues to contribute to major maternal and neonatal morbidity and mortality worldwide. In this article, we review the pathophysiological mechanisms, screening strategies, and novel therapeutic options for preeclampsia.