Context: The association of inpatient glucose measurements with amputations in patients admitted with acute diabetic foot has not been described. Objective: To evaluate the relationship of hyperglycemia, hypoglycemia, and glucose variability during hospitalization with amputations in patients hospitalized with acute diabetic foot. Design: Retrospective cohort study. Setting: Academic tertiary hospital. Patients: We reviewed demographic, clinical, laboratory, and point-of-care glucose data in patients hospitalized with acute diabetic foot in the Diabetic Foot Unit during 2015 through 2017. Main Outcome Measures: The primary outcomes were any or major amputations during hospitalization. Secondary outcomes included length of hospitalization and in-hospital mortality. Results: During the study period, 418 patients were hospitalized in the Diabetic Foot Unit and 45,496 glucose measurements were taken. Patients experiencing any hyperglycemia and any or severe hypoglycemia were more likely to undergo any or major amputations during hospitalization. High glycemic variability was associated with major amputations. Peripheral vascular disease (PVD), high Wagner score, and hypoglycemia were independent predictors of amputations. Older age, PVD, previous amputation, elevated white blood cell level, high Wagner score, and hypoglycemia were independent predictors of major amputations. Conclusions: In-patient hypoglycemia emerged as an independent risk factor for any and major amputations. Although it is unclear whether hypoglycemia directly contributes to adverse outcomes or is simply a biomarker of disease severity, efforts to minimize in-hospital hypoglycemic events are warranted.

Injuries to ligaments are common, painful and debilitating, causing joint instability and impaired protective proprioception sensation around the joint. Healing of torn ligaments usually fails to take place, and surgical replacement or reconstruction is required. Previously, we showed that in vivo application of the recombinant human amelogenin protein (rHAM⁺) resulted in enhanced healing of the tooth‐supporting tissues. The aim of this study was to evaluate whether amelogenin might also enhance repair of skeletal ligaments. The rat knee medial collateral ligament (MCL) was chosen to prove the concept. Full thickness tear was created and various concentrations of rHAM⁺, dissolved in propylene glycol alginate (PGA) carrier, were applied to the transected MCL. 12 weeks after transection, the mechanical properties, structure and composition of transected ligaments treated with 0.5 μg/μl rHAM⁺ were similar to the normal un‐transected ligaments, and were much stronger, stiffer and organized than control ligaments, treated with PGA only. Furthermore, the proprioceptive free nerve endings, in the 0.5 μg/μl rHAM⁺ treated group, were parallel to the collagen fibres similar to their arrangement in normal ligament, while in the control ligaments the free nerve endings were entrapped in the scar tissue at different directions, not parallel to the axis of the force. Four days after transection, treatment with 0.5 μg/μl rHAM⁺ increased the amount of cells expressing mesenchymal stem cell markers at the injured site. In conclusion application of rHAM⁺ dose dependently induced mechanical, structural and sensory healing of torn skeletal ligament. Initially the process involved recruitment and proliferation of cells expressing mesenchymal stem cell markers.

Aims: Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model.Methods: A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM⁺) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM⁺ using immunohistochemistry and immunofluorescence.Results: A total of 12 weeks after treatment, 0.5 μg/μl rHAM⁺ brought about significant repair of the subchondral bone and cartilage. Increased expression of proteoglycan and type II collagen and decreased expression of type I collagen were revealed at the surface of the defect, and an elevated level of type X collagen at the newly developed tide mark region. Conversely, the control group showed osteoarthritic alterations. Recruitment of cells expressing the mesenchymal stem cell (MSC) markers CD105 and STRO-1, from adjacent bone marrow toward the OCI, was noted four days after treatment.Conclusion: We found that 0.5 μg/μl rHAM⁺ induced in vivo healing of injured articular cartilage and subchondral bone in a rat model, preventing the destructive post-traumatic osteoarthritic changes seen in control OCIs, through paracrine recruitment of cells a few days after treatment.Cite this article: Bone Joint Res 2023;12(10):615–623.