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Purpose  CAGE-DR implant is a novel Food and Drug Administration approved intramedullary fracture fixation device used for distal radius fractures. We examine a series of 22 patients and report the outcomes with this device. Materials and Methods  A total of 24 patients with distal radius fractures (8 articular AO type C1/C2; 16 extra-articular AO type A2/A3) underwent open reduction and internal fixation (ORIF) using CAGE-DR implant by a single surgeon. Data including fracture type, angle of displacement, radiographic consolidation, grip strength, wrist range of motion (ROM), patient-rated wrist evaluation (PRWE), and Visual Analog Scale (VAS) pain scores were recorded at time of surgery and at standard follow-up. Results  All 24 patients underwent uneventful ORIF. At first follow-up visit (9 days), all patients had full digital ROM (measured as 0 cm tip-to-palm distance). Two patients were lost to follow-up. Eighteen of the remaining 22 patients had sufficient radiographic follow-up and all 18 demonstrated healing. At latest follow-up (mean 9.7 months, range, 3-20), VAS pain scores averaged 0.6 (range, 0-8) and PRWE averaged 12.1 (range, 0-53.5). Grip strength of the operated hand averaged 58 lbs (range, 20-130). ROM included: wrist flexion 73° (50-95), wrist extension 78° (60-110), pronation 77° (60-90), supination 79° (60-90), ulnar deviation 31° (5-45), and radial deviation 17° (10-30). Three patients underwent screw removal to prevent tendon irritation. One patient underwent hardware removal due to prominence on imaging but was asymptomatic. There were otherwise no major complications, including complex regional pain syndrome, in the series to date. Conclusion  The CAGE-DR fracture fixation system is a promising alternative to established methods of distal radius internal fixation. This series has a low reported pain score starting immediately postoperatively and a low complication rate. This novel device is a promising option for internal fixation of displaced distal radius fractures with a low complication profile. Level of Evidence  This is a level IV, therapeutic study.

Background  Iliac crest bone graft harvesting is routinely performed for upper extremity orthopedic procedures despite high complication rates associated with sensory nerve injury, hematoma, chronic pain, and fracture. Description of Technique  Cancellous bone graft is harvested from the proximal tibia using a medial approach, minimizing donor site morbidity. Patients and Methods  A retrospective review was undertaken of 14 patients who underwent cancellous proximal tibia bone graft harvesting to augment healing of wrist reconstruction, with 2 months minimum follow-up. We report donor limb tourniquet time, time to union, visual analog scale (VAS) pain score, and complications. Patients were also contacted by phone to administer a retrospective questionnaire and record experiences with the harvesting technique. Results  Average donor site VAS for the immediate postoperative period was 7.4. Average tourniquet time was 28 minutes. Average time to union of the recipient site was 45 days. One patient experienced delayed union after corrective osteotomy, attributed to osteoporosis. Two patients underwent hardware removal from the operative wrist, unrelated to bone graft harvesting. One patient with a history of chronic neuropathy and foot drop developed dysesthesia and allodynia about the ipsilateral ankle, but was asymptomatic at the proximal tibia donor site; ankle symptoms resolved 3 weeks postoperatively. No patient reported any residual donor site difficulties 24.2 months postoperatively. Conclusion  In consideration of the minimal complication rate, favorable clinical parameters, and excellent patient tolerance, we advocate proximal tibia bone graft harvesting as opposed to iliac crest harvesting for wrist reconstruction when a moderate amount of autogenous cancellous graft is needed. Level of Evidence  IV.

Background: Neointimal hyperplasia is a common cause of vein graft failure resulting from luminal narrowing and occlusion. Cilostazol is a U.S. Food and Drug Administration-approved phosphodiesterase III and platelet aggregation inhibitor commonly used in peripheral vascular disease. The authors studied whether topical cilostazol treatment at the time of vein grafting helps limit the development of neointimal hyperplasia in a rat model., Methods: Six experimental rats and six control rats underwent interposition vein grafting into the femoral artery, followed by a single topical dose of cilostazol applied around the vein graft in the experimental animals. After 4 weeks, grafts were harvested and underwent histologic staining of axial sections to visualize intima thickness and elastin/myocyte content. Quantification was performed to assess total intima area. The intima-to-media and the intima-to-sum of intima and media ratios were determined to control for discrepancies in overall graft size., Results: Cilostazol-treated grafts had a thinner intima layer with less myocyte content compared with control grafts, amounting to an 82 percent decrease in total intima area compared with controls. A similar trend was seen even after controlling for overall graft size, with 85 and 76 percent reductions seen in intima-to-media and intima-to-sum of intima and media ratios, respectively., Conclusions: A single intraoperative dose of cilostazol applied locally significantly reduced intima size and smooth muscle content in rat interposition vein grafts examined 4 weeks postoperatively. A topical dose of cilostazol at surgery may therefore be helpful in controlling neointimal hyperplasia and reducing the need for systemic medications to prolong vein graft patency.

Esophageal strictures are a common problem causing significant morbidity for affected patients. Most can be treated safely and successfully with esophageal dilation. We have treated two patients with post-radiation esophageal strictures so tight that standard dilation technique failed even with an aggressive approach. We utilized a technique for operative dilation of these strictures using both antegrade and retrograde endoscopes. This approach for refractory esophageal strictures has only twice been previously reported. In both patients, a gastrostomy was placed and an endoscope was subsequently passed from the stomach retrograde up to the level of the stricture. Another endoscope was passed from above down to the proximal portion of the stricture. Illuminating the stricture, using fluoroscopy, carefully passing a wire, and grasping and pulling the wire with forceps from the opposite endoscope allowed for safe passage through the stricture. Savary dilators were utilized to effectively dilate the strictures. A method for protection of the lumen for subsequent dilations by passing a small catheter through the stricture was also developed. This technique offers an option for patients with otherwise untreatable strictures, with the major advantage of visualization from above and below.

Cryptococcus neoformans is a fungal pathogen that has evolved over the past 40 million years into three distinct varieties or sibling species (gattii, grubii, and neoformans). Each variety manifests differences in epidemiology and disease, and var. grubii strains are responsible for the vast majority of human disease. In previous studies, alpha strains were more virulent than congenic a strains in var. neoformans, whereas var. grubii congenic a and alpha strains exhibited equivalent levels of virulence. Here the role of mating type in the virulence of var. grubii was further characterized in a panel of model systems. Congenic var. grubii a and alpha strains had equivalent survival rates when cultured with amoebae, nematodes, and macrophages. No difference in virulence was observed between a and alpha congenic strains in multiple inbred-mouse genetic backgrounds, and there was no difference in accumulations in the central nervous system (CNS) late in infection. In contrast, during coinfections, a and alpha strains are equivalent in peripheral tissues but alpha cells have an enhanced predilection to penetrate the CNS. These studies reveal the first virulence difference between congenic a and alpha strains in the most common pathogenic variety and suggest an explanation for the prevalence of alpha strains in clinical isolates.

Several dimorphic fungi are important human pathogens, but the origin and maintenance of virulence in these organisms is enigmatic, since an interaction with a mammalian host is not a requisite for fungal survival. Recently, Cryptococcus neoformans was shown to interact with macrophages, slime molds, and amoebae in a similar manner, suggesting that fungal pathogenic strategies may arise from environmental interactions with phagocytic microorganisms. In this study, we examined the interactions of three dimorphic fungi with the soil amoeba Acanthameobae castellanii. Yeast forms of Blastomyces dermatitidis, Sporothrix schenckii, and Histoplasma capsulatum were each ingested by amoebae and macrophages, and phagocytosis of yeast cells resulted in amoeba death and fungal growth. H. capsulatum conidia were also cytotoxic to amoebae. For each fungal species, exposure of yeast cells to amoebae resulted in an increase in hyphal cells. Exposure of an avirulent laboratory strain of H. capsulatum to A. castellanii selected for, or induced, a phenotype of H. capsulatum that caused a persistent murine lung infection. These results are consistent with the view that soil amoebae may contribute to the selection and maintenance of certain traits in pathogenic dimorphic fungi that confer on these microbes the capacity for virulence in mammals.

It has recently been proposed that the origin and maintenance of virulence in certain environmental fungi is influenced by their interactions with non-vertebrate hosts such as amoebae and nematodes. In prior studies we have shown that the interactions of the soil amoebae Acanthamoeba castellanii with Cryptococcus neoformans varieties neoformans and grubii resemble those with macrophages. Here we extend those studies to C. neoformans variety gattii and describe quantitative differences in the type and outcome of the interactions observed relative to the other varieties. C. neoformans var. gattii proliferated in the presence of A. castellanii but the interaction was primarily extracellular with a paucity of phagocytic events. Experiments with acapsular cells coated with polysaccharide suggest that differences in the capsule structure may be responsible for the different interactions between cells of varieties neoformans, grubii, and gattii with amoebae. The ability of C. neoformans var. gattii to exploit amoebae indicates that despite major biological differences between C. neoformans varieties, all retain the ability to be pathogenic for A. castellanii.

Cryptococcus neoformans is an encapsulated, environmental fungus that can cause life-threatening meningitis. Pathogenicity of C. neoformans for macrophages and vertebrate hosts may be a mechanism selected in evolution for protection against environmental predators. In this study, we investigated whether Dictyostelium discoideum could serve as an alternate host for C. neoformans. D. discoideum has a defined genetic system which provides significant advantages for the study of fungus-amoeba interactions. Our results show that D. discoideum is susceptible to infection with C. neoformans and that the interactions are similar to those described previously for this fungus with macrophages and Acanthamoeba castellanii. Acapsular C. neoformans cells did not replicate when coincubated with D. discoideum. However, incubation of acapsular C. neoformans with D. discoideum mutants defective in myosin VII synthesis resulted in infection, validating the concept that avirulent organisms can be virulent in impaired hosts even at the unicellular level. Phagocytosis of C. neoformans by D. discoideum could be inhibited with capsule-specific antibodies and various sugars. Passage of an encapsulated C. neoformans strain through D. discoideum cultures increased virulence and was accompanied by larger capsules and faster time to melanization. These results add to the evidence implicating soil ameboid predators as important factors for the maintenance of C. neoformans virulence in the environment and suggest that D. discoideum promises to be an extremely useful system for studying the interaction of C. neoformans with phagocytic cells.