Surgical site infection is one of the most severe complications of surgical treatments. However, the optimal procedure to prevent such infections remains uninvestigated. Ultraviolet radiation C (UVC) with a short wavelength has a high bactericidal effect; however, it is cytotoxic. Nonetheless, given that UVC with a wavelength of 222 nm reaches only the stratum corneum, it does not affect the skin cells. This study aimed to investigate the safety of 222-nm UVC irradiation and to examine its skin sterilization effect in healthy volunteers. This trial was conducted on 20 healthy volunteers. The back of the subject was irradiated with 222-nm UVC at 50–500 mJ/cm², and the induced erythema (redness of skin) was evaluated. Subsequently, the back was irradiated with a maximum amount of UVC not causing erythema, and the skin swabs before and after the irradiation were cultured. The number of colonies formed after 24 hours was measured. In addition, cyclobutene pyrimidine dimer (CPD) as an indicator of DNA damage was measured using skin tissues of the nonirradiated and irradiated regions. All subjects experienced no erythema at all doses. The back of the subject was irradiated at 500 mJ/cm², and the number of bacterial colonies in the skin swab culture was significantly decreased by 222-nm UVC irradiation. The CPD amount produced in the irradiated region was slightly but significantly higher than that of the non-irradiated region. A 222-nm UVC at 500 mJ/cm² was a safe irradiation dose and possessed bactericidal effects. In the future, 222-nm UVC irradiation is expected to contribute to the prevention of perioperative infection.

Although immobility is a common cause of muscle atrophy, the mechanism underlying this causality is unclear. We here show that Krüppel-like factor 15 (KLF15) and IL-6 are upregulated in skeletal muscle of limb-immobilized mice and that mice with KLF15 deficiency in skeletal muscle or with systemic IL-6 deficiency are protected from immobility-induced muscle atrophy. A newly developed Ca²⁺ bioimaging revealed that the cytosolic Ca²⁺ concentration ([Ca²⁺]_i) of skeletal muscle is reduced to below the basal level by immobilization, which is associated with the downregulation of Piezo1. Acute disruption of Piezo1 in skeletal muscle induced Klf15 and Il6 expression as well as muscle atrophy, which was prevented by antibodies against IL-6. A role for the Piezo1/KLF15/IL-6 axis in immobility-induced muscle atrophy was validated in human samples. Our results thus uncover a paradigm for Ca²⁺ signaling in that a decrease in [Ca²⁺]_i from the basal level triggers a defined biological event.

Background: Understanding the causative factors of fracture nonunion leads to both prevention and improvements in treatment. The purpose of this study was to understand the clinical characteristics and causative factors of nonunion in a case series. Methods: One hundred two consecutive patients with fracture nonunions of the extremities who were surgically treated in our hospital over the last decade were analyzed. Data were collected by reviewing medical charts. Radiographs were reviewed to classify the nonunion by radiographic appearance. Causative factors of nonunions were identified for each patient. Factors relating to inadequate mechanical stability or reduction and those relating to a decline in biological activity were investigated. Mechanical factors included inappropriate dynamization, inappropriate reduction, inappropriate surgical management, insufficient fixation, and conservative treatment. Surgical technical errors were identified through careful review by three experienced trauma surgeons. Biological activity factors included comminution and bone loss, open fracture, excessive surgical exposure, infection, previous radiation therapy, alcohol abuse, diabetes mellitus, smoking, genetic disorders, and metabolic disease or endocrine pathology. We also classified the causative factors as patient-dependent or patient-independent factors. Results: Of the 102 nonunions, 47 were oligotrophic, 22 were hypertrophic, 17 were atrophic, 12 were defect types, and 4 were comminuted. Twenty-four cases had factors of inadequate mechanical stability or reduction, 23 cases had biological factors, and 55 cases had both types of factors. Four cases had patient-dependent factors, 40 cases had patient-independent factors, and 58 cases had both types of factors. Conclusions: Our results demonstrated that there were a considerable number of nonunions with causative factors which can be improved, such as inadequate fracture management.

The discovery of microRNA (miRNA) has revealed a novel type of regulatory control for gene expression. Increasing evidence suggests that miRNA regulates chondrocyte, osteoblast, and osteoclast differentiation and function, indicating miRNA as key regulators of bone formation, resorption, remodeling, and repair. We hypothesized that the functions of certain miRNAs and changes to their expression pattern may play crucial roles during the process of fracture healing. Standard healing fractures and unhealing fractures produced by periosteal cauterization at the fracture site were created in femurs of seventy rats, with half assigned to the standard healing fracture group and half assigned to the nonunion group. At post-fracture days 3, 7, 10, 14, 21, and 28, total RNA including miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was performed with miRNA samples from each group on post-fracture day 14. For further analysis, we selected highly up-regulated five miRNAs in the standard healing fracture group from the microarray data. Real-time PCR was performed with miRNA samples at each time point above mentioned to compare the expression levels of the selected miRNAs between standard healing fractures and unhealing fractures and investigate their time-course changes. Microarray and real-time polymerase chain reaction (PCR) analyses on day 14 revealed that five miRNAs, miR-140-3p, miR-140-5p, miR-181a-5p, miR-181d-5p, and miR-451a, were significantly highly expressed in standard healing fractures compared with unhealing fractures. Real-time PCR analysis further revealed that in standard healing fractures, the expression of all five of these miRNAs peaked on day 14 and declined thereafter. Our results suggest that the five miRNAs identified using microarray and real-time PCR analyses may play important roles during fracture healing. These findings provide valuable information to further understand the molecular mechanism of fracture healing and may lead to the development of miRNA-based tissue engineering strategies to promote fracture healing.

Purpose: Fracture-related infections are difficult to treat because of the formation of biofilms around implants. Systemic antibiotics are notoriously ineffective against biofilms due to their insufficient penetration of tissues with poor vascularity. The goal of treating fracture-related infections is to achieve bone union while retaining the implant. Our proposal of continuous local antibiotic perfusion is a sustained local delivery system of sufficient antibiotics to bone and soft tissue infection sites, including to bone marrow via needles as intra-medullary antibiotics perfusion and to soft-tissue via double-lumen subcutaneous tubes as intra-soft tissue perfusion. Methods: In this study, we examined the outcomes of 40 patients treated for fracture-related infections using continuous local antibiotic perfusion between 2015 and 2021 at Steel Memorial Hirohata Hospital, Himeji, Japan. Result: The antibiotic used for continuous local antibiotic perfusion was gentamicin in all cases. Implant removal was required in five patients. Two patients required toe amputation and knee arthrodesis, while the remaining 38 patients achieved fracture union. Only one case of transient acute renal injury as a systemic side effect was observed, but it soon resolved. The blood concentration of gentamicin could be adjusted to less than the trough level. Conclusions: Continuous local antibiotic perfusion is a novel local drug delivery system that has the potential of delivering sufficient concentrations of antibiotics with few systemic side effects; it is a useful option for the treatment of fracture-related infections.