Biomimetic Engineering of a Scavenger-Free Nitric Oxide-Generating/Delivering System to Enhance Radiation Therapy.

Nitric oxide (NO) is a potent tumor-cell radiosensitizer but it can be readily scavenged by hemoglobin (Hb) in vivo. A biomimetic incubator that can generate and deliver NO in a scavenger (Hb)-free environment to enhance its radiosensitizing effect to maximize its efficacy in radiotherapy is proposed. This NO incubator comprises a poly(lactic-co-glycolic acid) (PLGA) hollow microsphere (HM) that contains an NO donor (NONOate) and a surfactant molecule (sodium caprate, SC) in its aqueous core. In acidic tumorous environments, the PLGA shell of the HM allows the penetration of protons from the outside, activating the hydrolytic cleavage of NONOate, spontaneously generating NO bubbles, which are immediately trapped/stabilized by SC. The SC-stabilized NO bubbles in the HM are then squeezed through the spaces of its PLGA matrices by the elevated internal pressure. Upon leaving the HM, the entrapped NO molecules may passively diffuse through their SC-stabilized/protected layer gradually to the tumor site, having a long-lasting radiosensitizing effect and inhibiting tumor growth. The entire process of NO generation and delivery is conducted in a scavenger (Hb)-free environment, mimicking the development of young ovoviviparous fish inside their mothers' bodies in the absence of predators before birth.

Superior Survivorship of Cementless vs Cemented Diaphyseal Fixed Modular Rotating-Hinged Knee Megaprosthesis at 7 Years' Follow-Up.

BACKGROUND: Total knee arthroplasty in the presence of a huge bone and soft-tissue defect is always a challenge. A rotating-hinged (RH) megaprosthesis is indicated for extensive soft-tissue loss with a huge bone defect such as a primary or metastatic neoplasm of the bone, repeat periprosthetic joint infection, or extensive trauma of the knee. However, the reported survivorship of RH megaprostheses is unsatisfactory. The aim of this study was to evaluate the survivorship of megaprostheses and the factors that contribute to implant survival. METHODS: A total of 103 RH knee megaprostheses were implanted in 85 patients between January 2001 and June 2013. Each prosthesis was a modular custom-made (CM) cemented or cementless fixed total knee system (United USTAR system). Clinical results and prosthesis survivorship were evaluated between the 2 groups. RESULTS: The overall survivorship of this CM knee megaprosthesis was 91% at 2 years, 83% at 5 years, and 68% at 10 years. The cumulative component survivorship was 87% in the cemented group and 96% in the cementless group at 2 years compared with 75% in the cemented group and 94% in the cementless group at 5 years. The failure mechanism included loosening in 5 and breakage in 6 patients in the cemented stem group. The survivorship of the cementless fixed component was significantly superior to that of the cemented fixed component. CONCLUSION: Our data suggest that modular RHCM knee megaprosthesis provides an acceptable clinical result. A diaphyseal long stem with cementless fixation was more reliable and durable than its cemented counterpart.

Incidence and Risk Factors for Extremity Osteoradionecrosis after Limb-Sparing Surgery and Adjuvant Radiotherapy.

Osteoradionecrosis (ORN) is a major complication after radiotherapy. Most studies on ORN have focused on patients with mandibular lesions, with few studies including patients with extremity soft tissue sarcoma (STS). We included 198 patients with extremity STS who underwent limb-sparing surgery and adjuvant radiotherapy between 2004 and 2017. The incidence rate of extremity ORN was 3.5% (7/198), with most lesions (6/7) located in the lower extremities. The mean follow-up time was 62 months. Clinical presentations included chronic ulcers, soft tissue necrosis, sinus discharge, bone nonunion, and pathological fractures. Compared with the non-ORN group, the ORN group had a significantly higher total radiation dose (68 Gy vs. 64 Gy, p = 0.048) and greater use of intraoperative periosteal stripping (p = 0.008). Repeat surgeries and subsequent soft tissue reconstruction or limb amputation were performed as treatments. The risk and management of ORN in patients with extremity STS was ignored previously. Because the disease is complex and affects both clinicians and patients, careful surveillance should be undertaken.

Nontuberculous mycobacteria peri-prosthetic joint infection: An outcome analysis for two stage revision arthroplasty.

PURPOSE: Nontuberculous mycobacteria periprosthetic joint infection (NTMPJI) is a rare complication of hip or knee joint arthroplasty. The experience for outcomes of NTMPJI treatment is still limited. The objective of this study was to investigate the outcome of hip or knee nontuberculous mycobacteria periprosthetic joint infection following treatment with two-stage exchange arthroplasty. MATERIAL AND METHODS: From 1995 to 2020, 12 patients with NTMPJI were treated with two-stage exchange arthroplasty at our institution. We collected and analyzed variables including demographic data, comorbidity, microbiological data, treatment outcome and antibiotic formula in bone cement. RESULTS: Mycobacterium abcessus (n = 6) and Mycobacterium chelonae (n = 2) constitute the majority of the cases. Five patients had early-onset PJIs and the other seven patients were late onset. The success rate of two-stage exchange arthroplasty was 66.7% (8 of 12). Three patients experienced infection relapse, and one patient had soft tissue compromise complication. Post-operative antibiotic therapy may not improve the success rate (4 of 6 cases, 66.7%). Based on in vitro study, the most commonly used effective antibiotic in bone cement spacer for nontuberculous mycobacteria was amikacin. CONCLUSIONS: nontuberculous mycobacteria is a rare cause of PJIs and should be suspected especially in relatively immunocompromised patients. Resection arthroplasty with staged reimplantation is the preferred approach. Prolonged post-operative antibiotic therapy before reimplantation may not improve the success rate. Delayed revision surgery may not be needed and can be performed once C-reactive protein level is normal after a drug holiday.

Dysregulated expression of antioxidant enzymes in polyethylene particle-induced periprosthetic inflammation and osteolysis.

Small wear particles (0.1-10 µm) in total joint replacement are generally considered as the major causative agent leading to periprosthetic inflammation and osteolysis. However, little is known about the roles of larger wear particles (10-100 µm) in periprosthetic inflammation and osteolysis. Additionally, although ample studies demonstrated that increased oxidative stress is critically involved in particle-induced inflammation and osteolysis, detailed changes in antioxidant enzymes expression in the disease development remain largely unclear. Herein, we used a rat knee prosthesis model to assess effects of polyethylene (PE) particles (20-60 µm) on the levels of oxidative stress markers such as malondialdehyde (MDA) and total antioxidant capacity (TAC) in blood plasma, and on the expression profiles of antioxidant enzymes in knee joint tissues. In combination with a forced-exercise intervention for all surgical rats, we found that the rat groups treated with both artificial joint and PE particles exhibited higher MDA levels and lower TAC levels, together with lower levels of physical activity and higher levels of inflammatory markers, than the sham group and the groups receiving artificial joint or PE particles alone at weeks 20-24 post-operatively. Dose-response relationships between the exposure to PE particles and the induction of oxidative stress and inflammation were also observed in the artificial joint/PE groups. Under such conditions, we unexpectedly found that most of antioxidant enzymes displayed pronounced up-regulation, with concomitant induction of inflammatory and osteoclast-inducing factors (including IL-1ß, NF-κB and RANKL), in the artificial joint/PE groups as compared to the sham, artificial joint only, or PE only group. Only a few antioxidant enzymes including SOD2 and GPx2 showed down-regulation. Collectively, our findings demonstrate that implantation of artificial joint along with large PE particles synergistically trigger the induction of oxidative stress; however, down-regulation of many antioxidant enzymes may not necessarily occur during the disease development.

Metal ion concentrations and semen quality in patients undergoing hip arthroplasty: A prospective comparison between metal-on-metal and metal-on-polyethylene implants.

PURPOSE: The widespread usage of metal-on-metal (MoM) articulations in total hip arthroplasty (THA) has been tempered by concerns of increased metal ion production. The purpose of the study is to evaluate the influence of metal ion exposure on semen quality in young male patients undergoing THA. METHODS: Male patients who were scheduled for unilateral THA and aged between 20 and 45 years were prospectively enrolled. Patients were sorted into MoM and metal-on-polyethylene (MoP) groups with equal case number. Semen and blood metal ion levels were measured and sperm analysis was performed before, 6 months after, and 1 year after surgery. RESULTS: Compared to preoperative baseline, patients (n = 50) in both groups had increased cobalt (Co) and chromium (Cr) concentrations in blood and seminal fluid after surgery. Between-group comparisons at 6 months and 1 year after surgery showed that patients in the MoM group both had a greater Co concentration in blood and semen and a greater Cr concentration in blood and semen. Patients receiving MoM prosthesis had a reduced percentage of morphologically normal sperm, and decreases from the preoperative level (44.7%) were significant at 6 months (36.8%, p = 0.03) and 1 year (33.8%, p = 0.004). CONCLUSIONS: Our data shows a significantly greater concentration of metal ion in blood and semen in patients with MoM prosthesis with a reduced percentage of morphologically normal sperm. Despite small effects on sperm quality, some concerns remain. Further studies are necessary to determine sources of metal ion and to investigate effects on male fertility.