ABSTRACT
Background: Due to its apparent efficacy and safety, dupilumab, a monoclonal antibody that blocks Interleukin 4 (IL-4) and Interleukin 13 (IL-13), has been approved for treating T-helper 2 (Th2) disorders. However, adverse effects like local injection site reactions, conjunctivitis, headaches, and nasopharyngitis have been reported. Sex differences are known to influence both adaptive and innate immune responses and, thus, may have a bearing on the occurrence of these adverse effects. Nevertheless, the literature lacks a comprehensive exploration of this influence, a gap this study aims to bridge. Materials and Methods: A comprehensive data mining of VigiBase, the World Health Organization (WHO) global pharmacovigilance database which contains case safety reports of adverse drug reactions (ADRs) was performed to test for sex -specific safety response to dual IL4/IL13 blockade by dupilumab. The information component (IC), a measure of the disproportionality of ADR occurrence, was evaluated and compared between males and females to identify potential sexual dimorphism. Results: Of the 94,065 ADRs recorded in the WHO global pharmacovigilance database, 2,001 (57.4%) were reported among female dupilumab users, and 1,768 (50.7%) were among males. Immune/autoimmune T-helper 1 (Th1)-, innate- and T-helper 17 (Th17)-driven diseases and degenerative ones were consistently reported with a stronger association with Dupilumab in males than females. Some adverse events were more robustly associated with Dupilumab in females. Conclusion: Dupilumab has an excellent safety profile, even though some ADRs may occur. The risk is higher among male patients, further studies, including ad hoc studies, are needed to establish causality.
ABSTRACT
INTRODUCTION: The incidence of incisional hernias (IH) after midline laparotomy varies from 11% to 20%. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is potentially prone to hernias because a Xiphoid to pubis laparotomy incision performed on patients who have undergone previous abdominal surgeries with the addition of chemotherapy and its related adverse effects. METHODS: We performed a retrospective analysis on a prospectively maintained single institution database from March 2015 to July 2020. The inclusion criteria were patients who underwent CRS-HIPEC and had at least 6 months postoperative follow-up with post-operative cross-sectional imaging study. RESULTS: Two hundred and one patients were included in the study. All patients underwent CRS-HIPEC with resection of previous scar and umbilectomy. Fifty-four patients were diagnosed with IH (26.9%). The major risk factors for IH in multivariate analysis were higher American society of Anesthesiologists score (ASA) (OR 3.9, P = 0.012), increasing age (OR 1.06, P = 0.004) and increasing BMI (OR 1.1, P = 0.006). Most of the hernia sites were median (n = 43, 79.6%). Eleven (20.4%) patients had lateral hernias due to stoma incisions or drain sites. Most of the median hernias were at the level of the resected umbilicus 58.9% (n = 23). Five (9.3%) of the patients with IH necessitated an urgent surgical repair. CONCLUSION: We have demonstrated that more than a quarter of the patients after CRS-HIPEC suffer from IH and up to 10% of them may require surgical intervention. More research is needed to find the appropriate intraoperative interventions to minimize this sequela.
