A systematic review of allometric scaling exponents for IgG mAbs.

Increasing complexity of mAbs in development creates challenges in predicting human pharmacokinetic (PK) parameters from preclinical data. The aim of this analysis was to identify optimal allometric scaling exponents.Data were extracted from literature to create a central database (currently the largest available published database) of two-compartment model parameters for mAbs (n = 59) in cynomolgus monkey (CM) and human.Global allometric exponents were calculated and drug-dependent factors were investigated as potential variables in determining the optimal scaling factor.The global exponents for scaling CM mAb PK data were 0.74 (CL), 0.80 (CL with Fc-modified mAbs excluded), 0.44 (CL with Fc-modified mAbs only), 0.71 (Q), 1.12 (V1), and 0.99 (V2). These values are in line with previously published literature values.

Venous injuries in pediatric trauma: Systematic review of injuries and management.

BACKGROUND: Diagnosis of vascular injury in pediatric trauma is challenging as clinical signs may be masked by physiologic compensation. We aimed to (1) investigate the prevalence of noniatrogenic pediatric venous injuries, (2) discuss options in management of traumatic venous injury, and (3) investigate mortality from venous injury in pediatric trauma. Our objective was to provide the practicing clinician with a summary of the published literature and to develop an evidence-based guide to the diagnosis and management of traumatic venous injuries in children. METHODS: A systematic review of published literature (PubMed) describing noniatrogenic traumatic venous injury in the pediatric population (<17 years) was performed according to PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses] guidelines. Data were retrieved systematically under the following headings: Study Design, Population Demographics (dates of recruitment, mean age, mechanism of injury), Diagnostic Approach, Vessel Injured, Management (operative technique), and Mortality. RESULTS: Thirteen articles were included in this systematic review. In total, 508 noniatrogenic traumatic venous injuries were reported in children between the year 1957 and present day. Mechanisms of injury included blunt trauma from seat belt-related injury and fall from height or penetrating trauma from gunshot and foreign object. Injury to the inferior vena cava was most frequently reported, followed by femoral vein and internal jugular injuries. Primary repair was the most frequently reported technique for surgical repair (38%), followed by ligation (25%) and end-to-end anastomosis (15%). Mortality in pediatric trauma patients who had venous injury was reported as 0% to 67% in published series, highest in the series in which the most frequently reported injury was of the inferior vena cava. CONCLUSION: Traumatic venous injury in the pediatric population is uncommon but may be associated with significant morbidity and mortality. Intra-abdominal venous injuries are associated with high mortality from exsanguination. Early diagnosis and intervention are therefore essential in such cases. LEVEL OF EVIDENCE: Systematic review, level IV.