Spine Involvement and Vertebral Deformity in Patients Diagnosed with Chronic Recurrent Multifocal Osteomyelitis.

BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory disorder of bone, typically arising adjacent to the physes of long bones but also seen throughout the skeleton. For patients with spinal involvement, CRMO lesions can cause compression deformities with a range of severity from minimal anterior wedging to circumferential height loss, known as vertebra plana. This study examines a large cohort of CRMO patients to determine the prevalence of spine involvement and vertebral deformity. METHODS: This is a retrospective review of all patients with a diagnosis of CRMO seen at our institution between January 2003 and December 2020. These patients were identified through a prospectively maintained database of all CRMO patients seen at the institution. A retrospective review was undertaken to identify all patients with spinal involvement and determine the prevalence of CRMO in the spine and its effects on vertebral height and deformity. RESULTS: Of 170 patients included in this study, 48 (28.2%) were found to have spinal involvement. Among patients with spinal involvement, vertebral body lesions were identified in 27 (56.3%) patients. The remaining lesions were in the sacrum or posterior elements. Radiographic evidence of the vertebral body height loss was noted in 23 of these 27 patients. CONCLUSIONS: This cohort of CRMO patients demonstrates that 28% of patients have spinal involvement, and 48% of those patients have vertebral body height loss. While the ideal treatment for spinal CRMO has yet to be determined, imaging studies, including whole-body MRI and spine-specific MRI, are useful in identifying vertebral lesions and deformities. Identification and surveillance of these lesions are important as the disorder has a relapsing and remitting course, and patients can develop significant vertebral body height loss. Once deformity has developed, we have seen no evidence of reconstitution of the height of the collapsed vertebra. Bisphosphonates have been successful in preventing the progression of vertebral body height loss. LEVEL OF EVIDENCE: Level II: Retrospective study investigating spinal involvement and prevalence of vertebral body deformity in patients diagnosed with CRMO.

Osteosarcoma in Pediatric and Adult Populations: Are Adults Just Big Kids?

Malignant bone tumors are commonly classified as pediatric or adolescent malignancies, and clinical trials for these diseases have generally focused on these populations. Of primary bone cancers, osteosarcoma is among the most common. Osteosarcoma has a bimodal age distribution, with the first peak occurring in patients from 10 to 14 years old, and the second peak occurring in patients older than 65, with about 25% of cases occurring in adults between 20 and 59 years old. Notably, adult osteosarcoma patients have worse outcomes than their pediatric counterparts. It remains unclear whether age itself is a poor prognostic factor, or if inherent differences in tumor biology exist between age groups. Despite these unknowns, current treatment strategies for adults are largely extrapolated from pediatric studies since the majority of clinical trials for osteosarcoma treatments are based on younger patient populations. In light of the different prognoses observed in pediatric and adult osteosarcoma, we summarize the current understanding of the molecular etiology of osteosarcoma and how it may differ between age groups, hypothesizing why adult patients have worse outcomes compared to children.

Graphene as a rational interface for enhanced adsorption of microcystin-LR from water.

Cyanotoxins such as microcystin-LR (MC-LR) represent a global environmental threat to ecosystems and drinking water supplies. The study investigated the direct use of graphene as a rational interface for removal of MC-LR via interactions with the aromatic ring of the ADDA1 chain of MC-LR and the sp2 hybridized carbon network of graphene. Intra-particle diffusion model fit indicated the high mesoporosity of graphene provided significant enhancements to both adsorption capacities and kinetics when benchmarked against microporous granular activated carbon (GAC). Graphene showed superior MC-LR adsorption capacity of 75.4 mg/g (Freundlich model) compared to 0.982 mg/g (Langmuir model) for GAC. Sorption kinetic studies showed graphene adsorbs 99% of MC-LR in 30 min, compared to zero removal for GAC after 24 hr using the same MC-LR concentration. Density functional theory (DFT), calculations showed that postulated π-based interactions align well with the NMR-based experimental work used to probe primary interactions between graphene and MC-LR adduct. This study proved that π-interactions between the aromatic ring on MC-LR and graphene sp2 orbitals are a dominant interaction. With rapid kinetics and adsorption capacities much higher than GAC, it is anticipated that graphene will offer a novel molecular approach for removal of toxins and emerging contaminants with aromatic systems.

Biodegradable microneedle patch for delivery of meloxicam for managing pain in cattle.

Microneedle patches are a promising source for transdermal diffusion of macromolecules and are designed to painlessly penetrate the skin. In this study, a biodegradable chitosan microneedle patch to deliver meloxicam for managing pain in cattle was tested. The potential of reuse of the polymeric solution to fabricate the patches, optimization of fabrication, morphological analysis of the microneedle patch and analysis of preservation of the chemical composition after sterilization were evaluated. In-vitro analysis consisted of studying in-vitro penetration mechanical properties, compression testing analysis of microneedle patch, and in-vitro drug release analysis. In-vivo studies were performed to analyze the dissolution capability of the microneedle patch. Results regarding the physical characteristics, chemical composition, and mechanical properties confirmed that rheological properties of the chitosan solution, present significant differences over time, demonstrating that reusing the solution on the fourth day results in failure patches. Morphological characteristics and chemical composition studies revealed that the process of sterilization (ethylene oxide gas) needed for implanting the patches into the skin did not affect the properties of microneedle patches. In-vitro studies showed that approximately 33.02 ± 3.88% of the meloxicam was released over 7 days. A full penetration of the microneedles into the skin can be obtained by applying approximately 3.2 N. In-vivo studies demonstrated that microneedle patches were capable of swelling and dissolving, exhibiting a dissolution percentage of more than 50% of the original height of microneedle after 7 days. No abnormal tissue, swelling, or inflammation was observed in the implanted area. The results of this work show that chitosan biodegradable microneedle patches may be useful to deliver meloxicam to improve pain management of cattle with positive effects for commercial manufacturing.

Graphene-Mediated removal of Microcystin-LR in chitosan/graphene composites for treatment of harmful algal blooms.

Water quality can be severely impacted by algal blooms alone, yet cyanotoxins, such as microcystin (MC), are potent underlying hazards produced by various species of cyanobacteria. Currently there is a need for environmentally compatible and economically viable media to address large scale application for HAB impacted waters. This study evaluated the interactions of chitosan/graphene (CSG) composites with three different species of cyanobacteria: Anabaena sp, Synechocystis sp, and Microcystis aeruginosa for both removal of algal optical density and toxins. Although results suggest that CSG has an algae dependent removal of density with a range of 40-90% removal, graphene/CSG is highly effective at MC toxin removal, removing >94% of MC-LR produced by Microcystis aeruginosa. Characterization by SEM and XRD revealed that 750 m2/g surface area graphene, imparts graphene morphology and functionality into the chitosan matrix surface, potentially enabling π-π interactions between graphene and the aromatic ring of microcystin. This proposed π-π removal mechanism of microcystin via the CSG chitosan biopolymer substrate offers a promising sustainable and selective media suitable for deployable treatment of HAB impacted waters.

Peptoid microsphere coatings: The effects of helicity, temperature, pH, and ionic strength.

Peptoids are peptidomimetic oligomers that predominantly harness similarities to peptides for biomimetic functionality. They have potential for use in biomedical applications and biosensors due to resistance to proteolytic degradation and low immunogenicity. The incorporation of chiral, aromatic side chains in the peptoid sequence allows for the formation of distinct secondary structures and self-assembly into supramolecular assemblies, including microspheres. Peptoid microspheres can be coated onto substrates for potential use in biosensor technologies, tissue engineering platforms, and drug-delivery systems. In order to be useful for these applications, the peptoid coatings must be robust under physiological conditions. In this study, we report the effects of various conditions on the peptoid microsphere coatings, including (i) helicity, (ii) temperature, (iii) pH, and (iv) ionic strength. These studies show that microsphere size decreases with increasing peptoid helicity and the positively charged side chains are positioned on the outside of the microspheres. The peptoid microsphere coatings are robust under physiological conditions but degrade in acidic conditions (pH < 7) and at low ionic strengths (<150 µM).

Clinical Care Guideline for Improving Pediatric Acute Musculoskeletal Infection Outcomes.

BACKGROUND: Acute pediatric musculoskeletal infections are common, leading to significant use of resources and antimicrobial exposure. In order to decrease variability and improve the quality of care, Children's Hospital Colorado implemented a clinical care guideline (CCG) for these infections. The purpose of this study is to evaluate clinical and resource outcomes PRE and POST this CCG. METHODS: Retrospective chart review evaluated patients admitted to a large pediatric quaternary referral center (CHCO) diagnosed with acute osteomyelitis, septic arthritis, pyomyositis, and/or musculoskeletal abscess prior to and after guideline implementation. Primary outcomes included length of stay and overall antibiotic use, with additional secondary clinical, process, and therapeutic outcomes examined. RESULTS: 82 patients were identified in both the pre-CCG and post-CCG cohorts. There was a reduction in the median of all primary outcomes, including length of stay (0.6 median days decrease, P = .04), length of IV antibiotic therapy (4.9 median days decrease, P < .0001), and days of IV antibiotic therapy (6.4 median days decrease, P = .0004). Our median length of stay post-CCG was 4.9 days, the shortest reported length of stay for pediatric acute musculoskeletal infections to date. Additionally, there was a 24.5 hour reduction in median length of fever (P = .02), faster CRP normalization (P < .0001), 50% decrease in the number of related readmissions (P = .02), 34% decrease in central venous catheters placed (P < .0001), decreased time to first culture (P = .02), and 79% pathogen identification post-CCG (P = .056). CONCLUSIONS: Implementation of a CCG for acute musculoskeletal infections improves patient, process and resource outcomes.