Postoperative Casting of Below-Knee Amputation Reduces StumpComplications.

BACKGROUND: Against the technological advances in limb salvage, below-the-knee amputation (BKA) remains a common procedure. Although most elective BKA is classified as clean operation, the reported stump complication rate is much higher than predicted. Postoperative casting (PC) may reduce the number of these complications. The aim of this study was to compare the efficacy of elastic bandage with knee immobilizer (EBKI) and PC in BKA stump complications. METHODS: Retrospective cohort comparison design identified patients who underwent BKA between 2000 and 2023 for non-correctable critical limb ischemia (CLI), or excessive tissue loss secondary to CLI, infection, severe neuropathy, or the combination of these and stratified them into 2 cohorts based on their postoperative stump dressing: EBKI and PC. BKAs that were done for trauma or neoplastic processes were excluded. The primary outcome measures: wound healing in 6 weeks and length of stay (LOS). SECONDARY OUTCOME MEASURES: stump injury, infection, dehiscence, necrosis, number of higher-level amputations, knee contracture, and post-BKA mobility with Special Interest Group of Amputee Medicine score. RESULTS: One hundred sixteen patients with 122 limbs (52 EBKI and 70 PC) were found who met inclusion criteria and analyzed. The groups were comparable in demographics and comorbidities and preoperative variables, including mobility. The primary wound healing at 6 weeks was higher (P = 0.007); wound dehiscence (P = 0.01) and LOS (P = 0.006) was lower in the PC group compared to EBKI group. The PC group achieved higher Special Interest Group of Amputee Medicine mobility score and lower number of contractures developed compared to the EBKI group. CONCLUSIONS: Applying and maintaining PC to the BKA stump during the first month of healing reduced the incidence of stump complications, shortened the LOS, and improved postrehabilitation mobility results. We found no effect of PC on postoperative infections, stump necrosis, and higher-level amputations.

Demonstration of Equivalence of Generic Glatiramer Acetate and Copaxone®.

The objective of the current work was to demonstrate the equivalence of Mylan's glatiramer acetate (GA) to that of the reference product Copaxone® (COP) using the four criteria for active pharmaceutical ingredient sameness as established by the US Food and Drug Administration (FDA). The reaction scheme used to produce Mylan's glatiramer acetate (MGA) was compared with that of COP, determined from publicly available literature. Comparative analyses of MGA and COP were performed for physicochemical properties such as amino acid composition and molecular weight distributions. Spectroscopic fingerprints were obtained using circular dichroism spectroscopy. Structural signatures for polymerization and depolymerization including total diethylamine (DEA) content, relative proportions of DEA-adducted amino acids, and N-and C-terminal amino acid sequences were probed with an array of highly sensitive analytical methods. Biological activity of the products was assessed using validated murine Experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis. MGA is produced using the same fundamental reaction scheme as COP and was shown to have equivalent physicochemical properties and composition. Analyses of multiple structural signatures demonstrated equivalence of MGA and COP with regard to polymerization, depolymerization, and propagational shift. Examination of the impact on prevention and treatment of EAE demonstrated equivalence of MGA and COP with respect to both activity and toxicity, and thereby provided confirmatory evidence of sameness. A rigorous, multi-pronged comparison of MGA and COP produced using an equivalent fundamental reaction scheme demonstrated equivalent physicochemical properties, structural signatures for polymerization and depolymerization, and biological activity as evidenced by comparable effects in EAE. These studies demonstrate the equivalence of MGA and COP, establishing active ingredient sameness by the US Food and Drug Administration (FDA) criteria for GA, and provide compelling evidence that the FDA-approved generic MGA can be substituted for COP for the treatment of patients with relapsing-remitting MS.

Postnatal Exocrine Pancreas Growth by Cellular Hypertrophy Correlates with a Shorter Lifespan in Mammals.

Developmental processes in different mammals are thought to share fundamental cellular mechanisms. We report a dramatic increase in cell size during postnatal pancreas development in rodents, accounting for much of the increase in organ size after birth. Hypertrophy of pancreatic acinar cells involves both higher ploidy and increased biosynthesis per genome copy; is maximal adjacent to islets, suggesting endocrine to exocrine communication; and is partly driven by weaning-related processes. In contrast to the situation in rodents, pancreas cell size in humans remains stable postnatally, indicating organ growth by pure hyperplasia. Pancreatic acinar cell volume varies 9-fold among 24 mammalian species analyzed, and shows a striking inverse correlation with organismal lifespan. We hypothesize that cellular hypertrophy is a strategy for rapid postnatal tissue growth, entailing life-long detrimental effects.

Polymorphism in generic drug product development.

The affect of polymorphism in the development of generic drug products is discussed. The desired polymorphic form is used based upon the ability to manufacture a bioequivalent product. The critical issues are control of the polymorphic form of the drug substance and the dissolution behavior of the drug product.