Localized deferoxamine injection augments vascularity and improves bony union in pathologic fracture healing after radiotherapy

BackgroundMedically based efforts and alternative treatment strategies to prevent or remediate the corrosive effects of radiotherapy on pathologic fracture healing have failed to produce clear and convincing evidence of success. Establishing an effective pharmacologic option to prevent or treat the development of non-unions in this setting could have immense therapeutic potential. Experimental studies have shown that deferoxamine (DFO), an iron-chelating agent, bolsters vascularity and subsequently enhances normal fracture healing when injected locally into a fracture callus in long bone animal models. Since radiotherapy is known to impede angiogenesis, we hypothesized that the pharmacologic addition of DFO would serve to mitigate the effects of radiotherapy on new vessel formation in vitro and in vivo.Materials and MethodsIn vitro investigation of angiogenesis was conducted utilizing HUVEC cells in Matrigel. Endothelial tubule formation assays were divided into four groups: Control, Radiated, Radiated + Low-Dose DFO and Radiated + High-Dose DFO. Tubule formation was quantified microscopically and video recorded for the four groups simultaneously during the experiment. In vivo, three groups of Sprague–Dawley rats underwent external fixator placement and fracture osteotomy of the left mandible. Two groups received pre-operative fractionated radiotherapy, and one of these groups was treated with DFO after fracture repair. After 40 days, the animals were perfused and imaged with micro-CT to calculate vascular radiomorphometrics.ResultsIn vitro, endothelial tubule formation assays demonstrated that DFO mitigated the deleterious effects of radiation on angiogenesis. Further, high-dose DFO cultures appeared to organize within 2 h of incubation and achieved a robust network that was visibly superior to all other experimental groups in an accelerated fashion. In vivo, animals subjected to a human equivalent dose of radiotherapy (HEDR) and left mandibular fracture demonstrated quantifiably diminished μCT metrics of vascular density, as well as a 75% incidence of associated non-unions. The addition of DFO in this setting markedly improved vascularity as demonstrated with 3D angiographic modeling. In addition, we observed an increased incidence of bony unions in the DFO treated group when compared to radiated fractures without treatment (67% vs. 25% respectively).ConclusionOur data suggest that selectively targeting angiogenesis with localized DFO injections is sufficient to remediate the associated severe vascular diminution resulting from a HEDR. Perhaps the most consequential and clinically relevant finding was the ability to reduce the incidence of non-unions in a model where fracture healing was not routinely observed.     

Molecular epidemiology of selected multidrug-resistant bacteria: a global report from the SENTRY Antimicrobial Surveillance Program

The SENTRY Antimicrobial Surveillance Program was initiated in 1997 as a global network for the longitudinal tracking of antimicrobial resistance and has incorporated a molecular typing protocol to detect and monitor emerging resistances in participant medical centers. Isolates with similar resistance profiles and patient demographics that were temporally related or those exhibiting emerging resistance phenotypes were routinely compared. Isolates were initially analyzed using the automated Riboprinter Microbial Characterization System (Qualicon, Inc., Wilmington, DE). Isolates with identical ribotype patterns were further characterized by pulsed field gel electrophoresis. During 2001, a total of 647 bacterial isolates were processed using this typing protocol; 36% were Staphylococcus aureus with multidrug-resistant, mupirocin- or quinupristin/dalfopristin-resistant phenotypes. Five ribotypes were predominant in this species with some occurring on more than one continent (184.5), whereas others were restricted to a single geographic region (893.2). Among S. aureus, 51 clusters demonstrating dissemination among patients were identified (31 medical centers). Twenty-three outbreaks/clusters were found among Enterobacteriaceae producing either extended-spectrum beta-lactamases or demonstrating resistance to fluoroquinolones. Carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. strains were also analyzed, some of which produced metallo-beta-lactamase enzymes. Clusters of carbapenem-resistant Acinetobacter were identified in Argentina and Israel, whereas metallo-beta-lactamase-producing P. aeruginosa epidemic strains were observed in Italy (three sites) and Brazil. The coupling of molecular epidemiologic investigations with global surveillance such as the SENTRY program adds significant value to participating medical centers and has proven to be effective in tracking changing trends and distribution of resistance genotypes both locally and globally.     

Tumoral calcinosis in postmenopausal women in urban India: an etiopathologic evaluation of 64 cases

Tumoral calcinosis (TC) is a distinct pathologic entity of obscure etiology, characterized by soft tissue calcium deposition. We analyzed 64 cases retrieved from surgical records over the last 15 years, to assess the disease pattern and recognize the various stages of the evolution of this lesion. In our study, most patients were women (53/64 cases), 47 of whom were postmenopausal, aged 51-70 years, belonging to lower socioeconomic strata, and involved with household chores. The hip was the most frequently affected site. Repeated trauma probably triggered calcium chelation and deposition at this site. Histologically, 10 cases belonged to stage II and 54 cases to stage III. Fully developed lesions showed chips of calcium surrounded by thick fibrosis, mimicking calcified parasite like the Guinea worm. Precursor lesions seen at the periphery of the main lesion suggests a possible etiological role for trauma. Postmenopausal hormonal imbalance, along with poor nutrition and repeated trauma led to TC in our women population. Awareness of its evolution can lead to a better understanding of the disease with possible therapeutic implications.     

Assessment of psychosocial impact of primary glaucoma and its effect on quality of life of patients in Western India

Purpose:To assess the impact of primary glaucoma of varying severity and duration on psychosocial functioning and quality of life of patients.Methods:A cross-sectional observational study was carried on 200 patients attending the glaucoma clinic of a tertiary care hospital in western India. After obtaining approval from the institutional ethics committee, written informed consent was taken. All patients underwent a thorough ophthalmic examination. Those with primary glaucoma were classified as per Hodapp–Parrish–Anderson criteria and asked to respond to the National Eye Institute Visual Function Questionnaire (NEIVFQ)-25 questionnaire. Responses were analyzed statistically.Results:Overall mean NEIVFQ 25 composite score was 74.4 ± 18.6. Mean scores were 87.0 (SD 7.2) for mild, 75.9 (SD 8.1) for moderate, and 47.0 (SD 13.7) for severe glaucoma groups. Lower scores were associated with males. Driving (62.2, SD 34.6) and ocular pain (63.5, SD 18.7) were maximally affected while color vision (90.1, SD 18.7) and social health (86.7, SD 20.1) were least affected. The duration of treatment had no effect on mean composite scores with impaired scores seen even in newly diagnosed cases. Age of the patient negatively correlated with NEIVFQ 25 composite score.Conclusion:With disease progression, the psychosocial functioning of the patients is negatively affected. This effect is irrespective of treatment duration and newly diagnosed cases can have impaired Quality of life scores. Quantification of psychosocial status along with education and counseling for all patients may play a definitive role in customizing treatment and providing patients with a better quality of Life.