Antibacterial, conductive, and osteocompatible polyorganophosphazene microscaffolds for the repair of infectious calvarial defect.

Many osteoconductive and osteoinductive scaffolds have been developed for promoting bone regeneration; however, failures would occur in osteogenesis when the defect area is significantly infected while the biomaterials have no antibacterial performances. Herein, a kind of multipurpose PATGP@PDA + Ag microspheres was prepared via emulsion method by using a conductive aniline tetramer (AT) substituted polyphosphazene (PATGP), followed by polydopamine (PDA) modification and silver nanoparticles (AgNPs) loading. The PATGP@PDA + Ag microspheres demonstrated a strong antibacterial activity against Staphylococcus aureus both in vitro and in vivo, while showing no cytotoxicity at an optimized AgNPs loading amount. Due to the electron-donor structure of the AT moieties, the PATGP@PDA + Ag microspheres displayed antioxidant capacities to scavenge reactive oxygen species (ROS). Due to their phosphorus-rich feature, the PATGP@PDA + Ag microspheres favored the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). As controls, nonconductive microspheres (PAGP@PDA, PAGP@PDA + Ag) were prepared similarly by using poly[(ethylalanine)(ethylglycyl)]phosphazene (PAGP). By co-implanting these microspheres with S. aureus into rat calvarial defects, among them, it was determined that the PATGP@PDA + Ag microspheres achieved the most abundant neo-bone formation, benefiting from their antibacterial, antioxidant and osteogenic activities. These results revealed that AgNPs loaded scaffolds made of conductive polyphosphazenes were promising for the regeneration of infected bone defects.

Soft Tissue, Bone, and Joint Infections in People Who Inject Drugs.

Infections are a common complication among people who inject drugs (PWID). Skin and soft tissue infections (SSTI) as well as bone and joint infections comprise a significant source of morbidity and mortality among this population. The appropriate recognition and management of these infections are critical for providers, as is familiarity with harm-reduction strategies. This review provides an overview of the presentation and management of SSTI and bone and joint infections among PWID, as well as key prevention measures that providers can take.

An innovative strategy to treat large metaphyseal segmental femoral bone defect using customized design and 3D printed micro-porous prosthesis: a prospective clinical study.

Five patients with segmental irregular-shaped bone defect of the femur were recruited in this study from 2017.12 to 2018.11. All patients were treated by customized design and 3D printed micro-porous prosthesis. And the procedure was divided into stages: radical debridement and temporary fixation (the first stage); the membrane formation and virtual surgery (intervening period for 6-8 weeks); definite reconstruction the defects (the second stage). Routine clinical follow-up and radiographic evaluation were done to assess bone incorporation and complications of internal fixation. The weight-bearing time and the joint function of the patients were recorded. The patients were followed up for an average of 16.4 months. The average length of bone defect and the distal residual bone was 12 cm and 6.5 cm. The average time of partial weight-bearing and full weight-bearing was 12.7 days and 2.6 months. X-ray demonstrated good osseous integration of the implant/bone interface. No complications occurred such as implant loosening, subsidence, loss of correction and infection. At the last follow-up, Harris score of hip joint was excellent in 2 cases, good in 2 cases, fair in 1 case; HSS score of knee joint was good in 4 cases, middle in 1 case. From our study, we concluded that meticulous customized design 3D printed micro-porous prosthesis combined with intramedullary nail may be a promising and an alternative strategy to treat metaphyseal segmental irregular-shaped femoral bone defect, especially for cases with massive juxta-articular bone loss.

Treponematosis in a pre-Columbian hunter-gatherer male from Antofagasta (1830 ± 20 BP, Northern Coast of Chile).

OBJECTIVE: This paper reports a new case of treponemal disease in a pre-Columbian hunter-gatherer inhabiting the desert coast of South America. MATERIALS: A well-preserved adult male skeleton from the "Vertedero Municipal" archaeological cemetery, located near the city of Antofagasta (Northern Chile). METHODS: The skeleton was radiocarbon dated, and isotopic analyses were performed to assess diet and mobility. Lytic and proliferative lesions identified were evaluated macroscopically and radiologically. RESULTS: A radiocarbon date of 1830 ± 20 BP and isotopic values indicating a marine diet and coastal residence were obtained. The cranium shows reactive changes as focal superficial cavitation, radial scarring and nodular cavitation, while the ribs, sternum, clavicles, and scapulae exhibit multiple lytic and proliferative lesions. The right femur has a node while both tibiae show mild anterior cortical thickening with a narrowed medullary cavity. CONCLUSIONS: Cranial lesions are pathognomonic for treponemal disease while postcranial changes are typical, and highly consistent with this pathology. SIGNIFICANCE: The type, morphology, and pattern of lesions make this case a good candidate for venereal syphilis. The case is relevant to the origin of venereal syphilis due to the lifestyle, temporal and ecological context of the individual. LIMITATIONS: Diagnosis of venereal syphilis is based on skeletal lesions; thus, it must be confirmed by molecular analysis. SUGGESTIONS FOR FURTHER RESEARCH: A comprehensive review of cases of pre-Columbian treponemal disease in South America as well as molecular studies are needed to confirm the presence of venereal syphilis in the New World before European contact.

Bone transport versus acute shortening for the management of infected tibial bone defects: a meta-analysis.

BACKGROUND: The treatment for infected tibial bone defects can be a great challenge for the orthopaedic surgeon. This meta-analysis was conducted to compare the safety and efficacy between bone transport (BT) and the acute shortening technique (AST) in the treatment of infected tibial bone defects. METHODS: A literature survey was conducted by searching the PubMed, Web of Science, Cochrane Library, and Embase databases together with the China National Knowledge Infrastructure (CNKI) and the Wanfang database for articles published up to 9 August 2019. The modified Newcastle-Ottawa scale (NOS) was adapted to evaluate the bias and risks in each eligible study. The data of the external fixation index (EFI), bone grafting, bone and functional results, complications, bone union time and characteristics of participants were extracted. RevMan v.5.3 was used to perform relevant statistical analyses. Standard mean difference (SMD) was used for continuous variables and relative risk (RR) for the binary variables. All of the variables included its 95% confidence interval (CI). RESULTS: Five studies, including a total of 199 patients, were included in the study. Statistical significance was observed in the EFI (SMD = 0.63, 95% CI: 0.25, 1.01, P = 0.001) and bone grafting (RR = 0.26, 95%CI: 0.15, 0.46, P < 0.00001); however, no significance was observed in bone union time (SMD = - 0.02, 95% CI: - 0.39, 0.35, P = 0.92), bone results (RR = 0.97, 95% CI: 0.91, 1.04, P = 0.41), functional results (RR = 0.96, 95% CI: 0.86, 1.08, P = 0.50) and complications (RR = 0.76, 95% CI: 0.41, 1.39, P = 0.37). CONCLUSIONS: AST is preferred from the aspect of minimising the treatment period, whereas BT is superior to AST for reducing bone grafting. Due to the limited number of trials, the meaning of this conclusion should be taken with caution for infected tibial bone defects.

Polylactic-co-glycolic acid microspheres added to fixative cements and its role on bone infected architecture.

Joint prostheses are an essential element to improve quality of life. However, prostheses may fail due to several factors, including the most frequent cause, Staphylococcus aureus infection. The identification of new fixing bone cements with less reactivity on bone tissue and an adequate response to infection remains a primary challenge. The aim of this study is to evaluate the response of bone tissue in rabbits after introduction of a hydroxyapatite-coated titanium rod with a commercial fixative cement (Palacos®) compared to a modified experimental cement (EC) containing polylactic-co-glycolic acid (PLGA) microspheres in the presence or absence of contaminating germs. This study used 20 New Zealand rabbits which were divided into four groups (n = 5) depending on the presence or absence of S. aureus and the use of commercial (Palacos®) or EC. A histological method, based on bone architecture damage, was proposed to evaluate from 1 to 9 the histological results and the response of the infected tissue. The macrophage response was also evaluated using monoclonal antibody RAM-11. The study showed better bone conservation with the use of EC with PLGA microspheres against the Palacos® commercial cement, including the noncontaminated and contaminated groups. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2517-2526, 2019.

Implantable antimicrobial biomaterials for local drug delivery in bone infection models.

Increased use of implantable biomedical devices demonstrates their potential in treating a wide variety of ailments and disorders in bone trauma and orthopaedic, reconstructive, and craniofacial applications. However, the number of cases involving implant failure or malfunction due to bacterial infection have also increased in recent years. Implanted devices can facilitate the growth of bacteria as these micro-organisms have the potential to adhere to the implant and grow and develop to form biofilms. In an effort to better understand and mitigate these occurrences, biomaterials containing antimicrobial agents that can be released or presented within the local microenvironment have become an important area of research. In this review, we discuss critical factors that regulate antimicrobial therapy to sites of bone infection, such as key biomolecular considerations and platforms for delivery, as well as current in vivo models and current advances in the field. STATEMENT OF SIGNIFICANCE: This review outlines the important factors that are taken into consideration for the development of biomaterials for local delivery of therapeutics to the site of bone infections. An overview of important criteria for development of this model (such as type of bone defect, antimicrobial therapeutic, and delivery vehicle) are provided, along with current research that utilizes these considerations. Additionally, this review highlights recent clinical trials that have utilized antimicrobial therapeutics for treatment of osteomyelitis.

Construction of injectable, pH sensitive, antibacterial, mineralized amino acid yolk-shell microspheres for potential minimally invasive treatment of bone infection.

INTRODUCTION: Treatment of infection within bone is difficult, and conventional surgical treatment brings intense pain to the patients physically and mentally. There is an urgent need to develop injectable nano- and/or micro-medicine for minimally invasive treatment of osteomyelitis. METHODS: In this paper, amino acid (L-lysine [Lys]) was mineralized into yolk-shell structured CaCO3 microspheres (MSs). The morphologies of the obtained MSs were investigated by scanning electron microscopy and transmission electron microscopy. The composition of CaCO3 MSs was identified by using Fourier transform infrared spectroscopy. The as-prepared CaCO3 MSs were examined with power X-ray diffraction analysis to obtain the crystallographic structure of the MSs. RESULTS: The as prepared Lys encapsulated CaCO3 MSs (Lys@CaCO3 MSs) were used as micro-drug to improve acidic environment of osteomyelitis caused by bacterial infection and promote osteoblast proliferation under oxidative stress. These pH responsive Lys@CaCO3 MSs have a drug loading efficiency of 89.8 wt % and drug loading content (DLC) of 22.3 wt %. CONCLUSION: Our results demonstrated that Lys@CaCO3 MSs can effectively kill Staphylococcus aureus and promote proliferation and differentiation of osteoblasts under stimulation of H2O2 at pH = 5.5.

SUCCESSFUL TREATMENT OF DIGITAL OSTEITIS BY INTRAVENOUS REGIONAL PERFUSION OF CEFTIOFUR IN AN AFRICAN ELEPHANT (LOXODONTA AFRICANA).

A 41-yr-old African elephant ( Loxodonta africana ) presented with a swollen third digit of the left forelimb and a 2-cm hole in the pad. Corrective trimming, topical treatments, and an oral antibiotic resulted in apparent resolution; however, it reoccurred after 4 mo. Radiographs suggested bone lysis in the third phalanx, with the primary differential diagnosis being septic osteitis. Flushing with metronidazole solution and intravenous regional perfusion (IVRP) of the foot were commenced. A tourniquet was applied just above the carpus, an interdigital vein was identified by ultrasound, and into this vein 2 g (20 ml) of ceftiofur sodium solution, followed by 60 ml of heparinized saline, was administered. The foot was kept raised for 25 min and then the tourniquet was removed. IVRP was repeated every other day for 70 treatments over 6 mo. Healing occurred, which was confirmed radiographically. IVRP offers an excellent treatment modality in a well-trained elephant.

Clinicopathologic correlation: mixed-density lesion in the posterior mandible.

A middle-aged man presented for evaluation of a mixed-density lesion of the left posterior mandible. This clinicopathologic correlation presents the radiographic, clinical, and histopathologic findings; differential diagnosis; and treatment plan for this case. The lesion was deemed to be of bacteriologic origin, likely a polymicrobial infection containing actinomycetes. Clinical care and follow-up for the patient are discussed.

Cutaneous Sinus Tract from Mandibular Second Molar with C-shaped Canal System and Improper Former Root Canal Treatment: A Case Report.

Here, we report the diagnosis and treatment of an extraoral cutaneous sinus tract originating in a mandibular second molar with a C-shaped root canal system. The patient was referred to our department by a dermatologist after a series of unsuccessful treatments, including antibiotics. Diffuse radiolucency on a preoperative radiograph revealed that earlier root canal treatment had been only partially successful. Consequently, we performed retreatment of the root canal comprising removal of the former restoration and gutta-percha, cleaning and shaping, and passive irrigation with sodium hypochlorite. The patient responded well, and the cutaneous lesion completely resolved uneventfully within 1 month postoperatively. Preoperative recognition and thorough knowledge of the root canal anatomy and conventional methods of obturation are necessary in performing successful endodontic treatment.

[Leishmania infantum induced bone lesions in a dog]. / Leishmania-infantum-bedingte Knochenläsionen bei einem Hund.

A 3-year-old Labrador Retriever originating from Spain was presented with a left-sided hind limb lameness for several months. The orthopedic examination revealed a pain response when palpating the left tarsal joint. Radiographic and computed tomographic studies showed polyostotic, aggressive osteolytic bone lesions with mild erosive arthritis. The diagnosis of canine leishmaniasis was confirmed by bone biopsy and the detection of the pathogen by PCR. Three weeks after initiation of therapy with allopurinol, the dog presented no signs of lameness. Eight months after start of therapy, radiographic examination revealed moderate regression of the osteolytic bone lesions.

Modeling Staphylococcus epidermidis-Induced Non-Unions: Subclinical and Clinical Evidence in Rats.

S. epidermidis is one of the leading causes of orthopaedic infections associated with biofilm formation on implant devices. Open fractures are at risk of S. epidermidis transcutaneous contamination leading to higher non-union development compared to closed fractures. Although the role of infection in delaying fracture healing is well recognized, no in vivo models investigated the impact of subclinical low-grade infections on bone repair and non-union. We hypothesized that the non-union rate is directly related to the load of this commonly retrieved pathogen and that a low-grade contamination delays the fracture healing without clinically detectable infection. Rat femurs were osteotomized and stabilized with plates. Fractures were infected with a characterized clinical-derived methicillin-resistant S. epidermidis (10(3), 10(5), 10(8) colony forming units) and compared to uninfected controls. After 56 days, bone healing and osteomyelitis were clinically assessed and further evaluated by micro-CT, microbiological and histological analyses. The biofilm formation was visualized by scanning electron microscopy. The control group showed no signs of infection and a complete bone healing. The 10(3) group displayed variable response to infection with a 67% of altered bone healing and positive bacterial cultures, despite no clinical signs of infection present. The 10(5) and 10(8) groups showed severe signs of osteomyelitis and a non-union rate of 83-100%, respectively. The cortical bone reaction related to the periosteal elevation in the control group and the metal scattering detected by micro-CT represented limitations of this study. Our model showed that an intra-operative low-grade S. epidermidis contamination might prevent the bone healing, even in the absence of infectious signs. Our findings also pointed out a dose-dependent effect between the S. epidermidis inoculum and non-union rate. This pilot study identifies a relevant preclinical model to assess the role of subclinical infections in orthopaedic and trauma surgery and to test specifically designed diagnostic, prevention and therapeutic strategies.

[Multiple sites extrapodal actinomycetoma: Favorable outcome to treatment with a combination of cotrimoxazole and NSAI]. / Mycétome actinomycosique extrapodal plurifocal : bonne réponse au traitement par l'association cotrimoxazole et AINS.

Mycetoma is a bacteriological or fungal infectious disease affecting the skin and/or soft tissues, which can be complicated by bone involvement. The most common feature is a tumor of the foot, but extrapodal localizations have been described. We report one case of a 47-year-old man who presented with tumefaction of a leg with multiple skin fistulae. Histopathological examination permitted to confirm the diagnosis of actinomycetoma and TDM showed the degree of bone and soft tissues involvement. Our case was characterized by the very inflammatory aspect of the tumor, its localization to the leg without foot involvement, the modest functional signs compared to the importance of radiological bone involvements, the deep destruction of the fibula while the tibia was apparently intact and the good response to treatment. In spite of its characteristic features, diagnosis of mycetoma is still late in our country, often with bone and/or articular spread. Priority may be given to measures for reduction of mycetoma diagnosis lateness.

The skeletal manifestation of malaria: An epidemiological approach using documented skeletal collections.

OBJECTIVES: Recent studies in paleopathology have shown promise in associating some skeletal lesions with malarial infection. However, malaria's skeletal manifestation has never been confirmed using a large clinical reference sample from an endemic area for malaria with known individual causes of death. MATERIALS AND METHODS: To pinpoint evidence of malaria infection on ancient skeletal remains, this study uses an epidemiological approach to compare skeletal lesions in a modern reference sample of 98 individuals from Uganda, where malaria is holoendemic, to a similar modern sample of 106 individuals from a malaria-free area. RESULTS: Five porous skeletal lesions are identified that appear more frequently in the endemic area population, especially in anemic individuals. These appear on the cranium, vertebral column, and humeral and femoral necks. Periostitis also associates strongly with individuals in the endemic population; however, linear enamel hypoplasias show an inverse association. The identified lesions are tested for their association with each other, and then tested individually for their diagnostic power through measures of sensitivity and specificity. A diagnostic outcome algorithm is formed from the remaining skeletal lesions and their inter-lesion associations. DISCUSSION: Several etiological explanations for the characteristic malarial skeletal lesions are explored, including severe malarial anemia, an imbalance in bone remodeling, and extramedullary erythropoiesis. The importance of careful differential diagnoses between other infectious and noninfectious causes of these lesions is discussed, including the potential for coinfection of malaria with other infectious diseases. The findings of this study are pivotal in establishing diagnostic criteria by which we can identify the prevalence and impact of malaria on past populations.

Hydatid cyst of bone.

Hydatid disease is an extremely uncommon differential diagnosis in the cystic/lytic lesions of bone. We present a rare case of echinococcal infection of femur which presented as pathological fracture in a middle-aged female and diagnosis was confirmed by histopathology. Hydatid disease of bone is often asymptomatic, and its diagnosis is usually made when lesions have become extensive.

INTRAOSSEOUS PROLIFERATIVE SPARGANOSIS PRESENTING AS A PATHOLOGICAL FRACTURE: A CASE REPORT AND REVIEW OF THE LITERATURE.

We report a case of 63-year-old male, who presented with pathological fracture of left distal humerus 3 weeks previously. The radiographic findings showed an ill-defined permeative osteolytic lesion of the left distal humerus. Incisional biopsy and debridement was done; pathological examination revealed a folded cestode larva with calcareous corpuscles in the bone and soft tissue, and increased eosinophils. IgG antibody tests for sparganosis were positive. The patient refused to have surgery for internal fixation and placement of an endoprosthesis.