Objective To minimize maintenance immunosuppression in upper-extremity transplantation to favor the risk-benefit balance of this procedure. Background Despite favorable outcomes, broad clinical application of reconstructive transplantation is limited by the risks and side effects of multidrug immunosuppression. We present our experience with upper-extremity transplantation under a novel, donor bone marrow (BM) cell-based treatment protocol (“Pittsburgh protocol”). Methods Between March 2009 and September 2010, 5 patients received a bilateral hand (n = 2), a bilateral hand/forearm (n = 1), or a unilateral (n = 2) hand transplant. Patients were treated with alemtuzumab and methylprednisolone for induction, followed by tacrolimus monotherapy. On day 14, patients received an infusion of donor BM cells isolated from 9 vertebral bodies. Comprehensive follow-up included functional evaluation, imaging, and immunomonitoring. Results All patients are maintained on tacrolimus monotherapy with trough levels ranging between 4 and 12 ng/mL. Skin rejections were infrequent and reversible. Patients demonstrated sustained improvements in motor function and sensory return correlating with time after transplantation and level of amputation. Side effects included transient increase in serum creatinine, hyperglycemia managed with oral hypoglycemics, minor wound infection, and hyperuricemia but no infections. Immunomonitoring revealed transient moderate levels of donor-specific antibodies, adequate immunocompetence, and no peripheral blood chimerism. Imaging demonstrated patent vessels with only mild luminal narrowing/occlusion in 1 case. Protocol skin biopsies showed absent or minimal perivascular cellular infiltrates. Conclusions Our data suggest that this BM cell-based treatment protocol is safe, is well tolerated, and allows upper-extremity transplantation using low-dose tacrolimus monotherapy.

Background: Academic plastic surgery has a history of underrepresentation of ethnic and racial minority groups. Recent policy shifts by national medical groups and plastic surgery societies have focused on reversing these inequalities. This study seeks to measure ethnic and racial representation at academic and leadership positions following recent changes. Methods: A cross-sectional study was conducted in June of 2018, measuring ethnic and racial diversity of U.S. academic plastic surgery faculty. Among faculty, career qualifications, years of experience, faculty positions, and leadership ethnicity were compared. Results: A total of 930 academic plastic surgeons were included in the study. Classified collectively as nonwhite, this group graduated more recently than other academic plastic surgeons (2006 versus 2001; p < 0.0001) and had greater rates of clinical fellowship attainment (OR, 1.62; 95 percent CI, 1.16 to 2.26). Nonwhite individuals were less likely to be employed in the full professor position compared with their white colleagues (OR, 0.6; 95 percent CI, 0.42 to 0.88; p = 0.0077). However, after adjustment for differences in years of postresidency experience, this disparity was no longer significant (OR, 1.06; 95 percent CI, 0.62 to 1.83; p = 0.82), indicating the importance of current cohort experience differences. Assessment of program leadership found that nonwhite chairs employed significantly more nonwhite faculty (42.5 percent versus 20.9 percent; p < 0.0001). Conclusions: Academic plastic surgery continues to face disparities in representation of both ethnic and racial minorities. Current inequalities are most severe at senior academic positions and may be linked to cohort experience differences along with leadership and promotion biases.

The results suggest that T cells and orbital fibroblasts participate in an antigen-dependent positive feedback loop in which presentation of autoantigens by fibroblasts via MHC class II and CD40-CD40L signaling results in T-cell activation. These activated T cells stimulate fibroblast proliferation, leading to fibroblast-associated diseases in GO. Thus, therapies that interfere with CD40-CD40L signaling, antigen expression by fibroblasts, or T-cell function may be effective in preventing progression of GO symptoms.

Zinc replenishment of NMBA-treated ZD rats rapidly induces apoptosis in esophageal epithelial cells and thereby substantially reduces the development of esophageal cancer.

The effects of genistein (Gn), sodium azide (naz), and dexamethasone (dxm) on testicular cells TM3, TM4 and GC-1 spg were studied in vitro. First, a series of experiments were performed to assess the response of the cells to the exposure of Gn, naz, dxm, a combination of Gn with naz and Gn with dxm. Trypan blue exclusion assay was used to determine the percentage of viability, and LDH-cytotoxicity test was used to assess the degree of treatment-induced cytotoxicity on each cell type. A second series of experiments were performed to study cytomorphology and determine the type and percentage of treatment-induced cell death (apoptosis and necrosis) on each cell line, using fluorescent dye technique to detect apoptotic and necrotic cells, and tunnel assay to confirm apoptosis. The results from the data obtained demonstrated: i) that incubation of testis cells with each of the agents (Gn, dxm, naz) alone and in two combinations (Gn-dxm, and Gn-naz) induced significant testicular cell death; ii) that both genistein and dexamethasone mostly and significantly induced apoptotic cell death while sodium azide induced necrotic cell death; iii) that addition of dexamethasone to genistein demonstrated synergism in apoptosis on testis cells; and iv) that combination of naz with Gn demonstrated synergism in necrosis on testis cells even though Gn alone did not induce significant necrosis. It is concluded that the synergistic actions of genistein and dxm, and of genistein + sodium azide in induction of apoptosis and/or necrosis may be of clinical and pathophysiological research interest considering the chemopreventive and chemotherapeutic potential of genistein; and the clinico-pharmacological application of dexamethasone and sodium azide.