BRAF inhibitor and hairy cell leukemia-related transient acantholytic dermatosis

Grover disease (GD) is an acquired, nonfamilial, nonimmune mediated, transient or persistent acantholytic dermatosis. Herein, we present a 72-year-old man who had clinical and histopathologic findings of GD following two weeks of treatment with vemurafenib without MEK inhibitor. The patient was successfully treated with topical emollients and a high-potency corticosteroid. Meanwhile, vemurafenib was temporarily discontinued. Drug-induced GD has increasingly been reported in patients on BRAF inhibitor monotherapy as an immune-related adverse event. The cutaneous side effects seem to arise secondary to a paradoxical activation of the mitogen-activated protein kinase signaling of BRAF inhibitor treatment, leading to keratinocyte proliferation. Although the pathogenesis of GD has not been delineated, there is suggestion of activation of T lymphocytes, particularly helper cells under the action of pro-inflammatory cytokines, resulting in proliferation of keratinocytes. Combination therapy with a MEK inhibitor appears to prevent BRAF-induced GD. Given that there is a higher prevalence of GD in patients with hematologic malignancy, a direct causal relationship between the initiation of vemurafenib therapy and development of GD in this case may be difficult to establish

Deferoxamine: potential novel topical therapeutic for chronic wounds

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136734/1/bjd14956.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136734/2/bjd14956_am.pd

Role of parathyroid hormone therapy in reversing radiation‐induced nonunion and normalization of radiomorphometrics in a murine mandibular model of distraction osteogenesis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101851/1/hed23216.pd

Stem Cell Therapy Remediates Reconstruction of the Craniofacial Skeleton After Radiation Therapy

This study utilized transplanted bone marrow stromal cells (BMSCs) as a cellular replacement therapy to remedy radiation-induced injury and restore impaired new bone formation during distraction osteogenesis (DO). BMSC therapy brought about the successful generation of new bone and significantly improved both the rate and quality of a bony union of irradiated, distracted [X-ray radiation therapy (XRT)/DO] murine mandibles to the level of nonirradiated DO animals. The bone mineral density and bone volume fraction were also significantly improved by the BMSC replacement therapy showing no difference when compared to nonirradiated animals. Finally, a biomechanical analysis examining the yield, failure load, and ultimate load also demonstrated a significantly improved structural integrity in BMSC-treated XRT/DO mandibles over XRT/DO alone. These results indicate that administration of BMSCs intraoperatively to a radiated distraction gap can function as an adequate stimulant to rescue the ability for irradiated bone to undergo DO and produce a healed regenerate of a vastly superior quality and strength. We believe that the fundamental information on the optimization of bone regeneration in the irradiated mandible provided by this work has immense potential to be translated from the bench to the bedside to lead to improved therapeutic options for patients suffering from the disastrous sequelae of radiation therapy.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140201/1/scd.2012.0472.pd

Targeting angiogenesis as a therapeutic means to reinforce osteocyte survival and prevent nonunions in the aftermath of radiotherapy

BackgroundRadiotherapy (XRT) exerts detrimental collateral effects on bone tissue through mechanisms of vascular damage and impediments to osteocytes, ultimately predisposing patients to the debilitating problems of late pathologic fractures and nonunions. We posit that angiogenic therapy will reverse these pathologic effects in a rat model of radiated fracture healing.MethodsThree groups of rats underwent mandibular osteotomy. Radiated groups received a fractionated 35‐Gy dose before surgery. The deferoxamine (DFO) group received local injections postoperatively. A 40‐day healing period was allowed before histology. Analysis of variance (ANOVA; p < .05) was used for group comparisons.ResultsRadiated fractures revealed a significantly decreased osteocyte count and corresponding increase in empty lacunae when compared to nonradiated fractures (p = .001). With the addition of DFO, these differences were not appreciated. Further, a 42% increase in bony unions was observed after DFO therapy.ConclusionTargeting angiogenesis is a useful means for promoting osteocyte survival and preventing bone pathology after XRT. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1261–1267, 2015Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113164/1/hed23744.pd