Induction of Endotoxin Tolerance Delays Acute Rejection in a Hindlimb Transplantation Model in Rats.

BACKGROUND: Acute rejection is seen in 85 percent of composite vascular allogeneic transplants despite long-term immunosuppression. Recently, it was reported that the induction of endotoxin tolerance prolonged heart allograft survival in mice. However, it produced side effects in all the animals secondary to the inflammatory reaction. Galactomannan has shown endotoxin tolerance without this side effect in vitro. The authors hypothesized that galactomannan-induced endotoxin tolerance delays acute rejection in vascular allogeneic transplantation without the side effects produced by lipopolysaccharide. METHODS: Twenty-four rat hindlimb transplants were divided into four groups according to the preconditioning received: control, lipopolysaccharide (0.16 ml/kg), galactomannan 72 hours before (galactomannan-72) (8 ml/kg), and galactomannan 24 hours before (galactomannan-24) (8 ml/kg). Median acute rejection time, weight loss, and diarrheal episodes were monitored. Blood samples were collected at 0, 7, 21, 30, 45, and 60 days. Plasma cytokines (i.e., tumor necrosis factor alpha, interferon gamma), peripheral chimerism, and lymphocyte percentages were analyzed. RESULTS: Median allograft survival was 40 days (range, 40 to 44 days) in the control group, 68 days (range, 61 to 71 days) in the lipopolysaccharide group, and 70 days (range, 69 to 73 days) in both galactomannan groups (p = 0.001). Weight loss was higher in the lipopolysaccharide group (p < 0.001), as was the 83.3 percent rate of diarrheal episodes (control, 0 percent, p = 0.015; galactomannan-72, 0 percent, p = 0.015; and galactomannan-24, 16.7 percent, p = 0.02). Preconditioned rats had higher peripheral blood chimerism (lipopolysaccharide, 2.30 ± 0.13 percent; galactomannan-72, 2.63 ±1.46 percent; and galactomannan-24, 2.47 ± 0.19 percent) compared to the control group (2.06 ± 0.36 percent) (lipopolysaccharide, p = 0.04; galactomannan-72, p = 0.002; and galactomannan-24, p = 0.002). CONCLUSIONS: Induction of endotoxin tolerance delays acute rejection in the rat hindlimb transplantation model. Galactomannan preconditioning has no lipopolysaccharide side effects and was equally effective in delaying acute rejection. CLINICAL RELEVANCE STATEMENT: The contributions of this experimental work are very incipient. Although the use of galactomannan in clinical practice requires more studies to assess its safety, there is no doubt that immunomodulation may be one of the responses that solve the problem of long-term immunosuppression.

Seguridad y complicaciones en reconstrucción mamaria autóloga con colgajo DIEP: una revisión sistemática / Safety and complications of autologous DIEP flap breast reconstruction: a systematic review

La reconstrucción mamaria microquirúrgica con tejido autólogo puede asociar complicaciones relacionadas con el colgajo y la zona donante. Nuestro objetivo fue valorar la evidencia clínica en seguridad, complicaciones y factores de riesgo en pacientes reconstruidas con colgajo de perforantes basado en la arteria epigástrica inferior profunda (DIEP). Se realizó una revisión sistemática en Medline de artículos publicados entre septiembre de 1995 y septiembre de 2015. Se recogieron las características demográficas de las pacientes, las medidas de los colgajos y las complicaciones de la cirugía incluyendo la necrosis completa, la necrosis parcial y la necrosis grasa. Se identificaron 34 artículos que incluían 35 series de casos, 2.761pacientes y un total de 3.927colgajos. La media del índice de masa corporal fue superior a 24,5kg/m2, mientras que la tasa de obesidad se situó por encima del 14,5%. Ningún artículo aportó información acerca del peso, superficie o volumen del colgajo tras su tallado en la zona receptora. Las tasas de necrosis completa y parcial fueron del 1,9% (75/3.811) y del 2,6% (68/2.575) respectivamente. La necrosis grasa se diagnosticó en el 8,2% (308/3.746) de los colgajos, con una desviación estándar de 6,9. El 5,5% (107/1.940) de los colgajos requirieron reintervención quirúrgica. La incidencia de hematoma en la zona receptora y de hernia o debilidad abdominal fue de un 3% (59/1.952 colgajos y 52/1.725 pacientes). En conclusión, la incidencia de complicaciones en reconstrucción mamaria con colgajo DIEP fue baja, aunque la necrosis grasa presentó una dispersión elevada (AU)

Autologous free flap breast reconstruction may be associated with complications related to the flap and the donor site. Our objective was to evaluate the reported evidence on safety, complications and risk factors in patients undergoing deep inferior epigastric artery perforator flap (DIEP) breast reconstruction. A systematic review was conducted based on a Medline search for studies published between September 1995 and September 2015. Demographic data, flap dimensions and complication rates were recorded including total flap necrosis, partial flap necrosis and fat necrosis. A total of 34 clinical studies including 35 case series, 2,761 patients and 3,927 DIEP flaps were identified. The mean body mass index was higher than 24.5kg/m2 whereas the obesity rate was above 14.5%. None of the articles reported flap weight, area or volume after molding. Total and partial flap necrosis rates were 1.9% (75/3,811) and 2.6% (68/2,575), respectively. Fat necrosis was diagnosed in 8.2% (308/3,746) of flaps with a standard deviation of 6.9. Reoperation was required in 5.5% (107/1,940) of the flaps. The incidence of hematoma in the recipient site and abdominal hernia or bulge formation was 3% (59/1,952 flaps and 52/1,725 patients). In conclusion, the occurrence of complications in breast reconstruction by autologous DIEP flap was low, although the occurrence of fat necrosis ranged widely (AU)

Algorithmic surgical enhancement of function after finger revascularisation.

Secondary surgical procedures can improve the function of revascularised and replanted digits. We describe the case of a patient who underwent multidigit revascularisation and replantation following a saw injury at flexor tendon Zone II. To achieve maximal functional improvement after finger revascularisation, we performed secondary surgical procedures in an order that was determined by following a reconstructive decision procedure that covered late revascularisation, nerve reconstruction, pedicled vascularised joint transfer, staged flexor tendon reconstruction and skin revision. Performing the procedures in this manner ensured overall safety. The patient's disabilities of the arm, hand and shoulder questionnaire score improved by 45 points, and the patient was able to return to work with an almost complete range of motion.

Effect of Cold Preservation on Chronic Rejection in a Rat Hindlimb Transplantation Model.

BACKGROUND: Previous studies on solid organ transplantation have shown that cold ischemia contributes to the development of chronic allograft vasculopathy. The authors evaluated the effect of cold ischemia on the development of chronic rejection in vascularized composite allotransplantation. METHODS: Thirty rat hindlimbs were transplanted and divided into two experimental groups: immediate transplantation and transplantation after 7 hours of cold ischemia. The animals received daily low-dose immunosuppression with cyclosporine A for 2 months. Intimal proliferation, arterial permeability rate, leukocyte infiltration, and tissue fibrosis were assessed. The CD3, CD4, CD8, CD20, and CD68 cells per microscopic field (200×) were counted, and C4d deposition was investigated. Cytokine RNA analysis was performed to measure tumor necrosis factor-α, interleukin-6, and interleukin-10 levels. RESULTS: Significant differences were found in the intimal proliferation and arterial permeability rate between the two groups (p = 0.004). The arterial permeability rate worsened in the most distal and small vessels (p = 0.047). The numbers of CD3, CD8, CD20, and CD68 were also statistically higher in the cold ischemia group (p < 0.05, all levels). A trend toward significance was observed with C4d deposition (p = 0.059). No differences were found in the RNA of cytokines. CONCLUSIONS: An association between cold ischemia and chronic rejection was observed in experimental vascularized composite allotransplantation. Chronic rejection intensity and distal progression were significantly related with cold ischemia. The leukocyte infiltrates in vascularized composite allotransplantation components were a rejection marker; however, their exact implication in monitoring and their relation with cold ischemia are yet to be clarified.

Safety of salvaging impending flap congestion in breast reconstruction by venous supercharging of the cephalic vein.

Autologous flap breast reconstruction is an established technique that carries a risk of vascular failure. We evaluated the safety of salvaging impending venous congestion by using the cephalic vein for supercharging autologous abdominal flaps. Our main outcome measures were flap survival, triggering or impairing lymphedema as measured by the physician or reported by the patient, and scar severity as measured by the Vancouver scar scale. We were able to save 100% of the flaps, but could not find any statistical association with or without increased lymphedema before and after the procedure. One patient reported that lymphedema worsened. The patients accepted the scars (mean Vancouver scar scale score, 5.7). In sum, using the cephalic vein to improve venous drainage of autologous breast reconstruction was safe and did not trigger or impair lymphedema, but scarring in the upper arm was unavoidable.

Factors influencing acute rejection of human hand allografts: a systematic review.

Acute rejection (AR) of human hand allografts (HHAs) may carry a risk of graft loss and leads to the need for immunosuppressive treatment. The literature on HHAs was reviewed to determine and evaluate the factors that trigger AR of HHAs. Clinical case reports of hand allograft transplantation published between 1999 and 2011 in English, French, or German were reviewed systematically. The number of AR episodes was the main outcome measure. Sixty-eight episodes of AR were described in 28 recipients. Calcineurin inhibitor-based maintenance regimens were associated with significantly fewer AR episodes than non-calcineurin inhibitor-based regimens (mean 1.9 vs 3.2; P = 0.018). In recipients who experienced cytomegalovirus infection, the mean number of episodes of AR was 4, whereas in those who did not experience cytomegalovirus infection it was 2.25 (P = 0.024). The planning of hand allograft transplantation should take these factors into account to minimize the risk of AR.

Outcomes with respect to disabilities of the upper limb after hand allograft transplantation: a systematic review.

The aim of this work is to compare disabilities of the upper limb before and after hand allograft transplantation (HAT), and to describe the side effects of immunosuppressive (IS) agents given to recipients of hand allografts. Clinical cases of HAT published between 1999 and 2011 in English, French, or German were reviewed systematically, with emphasis on comparing disabilities of the arm, shoulder and hand (DASH) scores before and after transplantation. Duration of ischemia, extent of amputation, and time since amputation were evaluated for their effect on intrinsic musculature function. Infectious, metabolic, and oncological complications because of IS therapy were recorded. Twenty-eight patients were reported in 56 clinical manuscripts. Among these patients, disabilities of the upper limb dropped by a mean of 27.6 (±19.04) points on the DASH score after HAT (P = 0.005). Lower DASH scores (P = 0.036) were recorded after secondary surgery on hand allografts. The presence of intrinsic muscle function was observed in 57% of the recipients. Duration of ischemia, extent of transplantation, and time since amputation were not associated statistically with the return of intrinsic musculature function. Three grafts were lost to follow-up because of noncompliance with immunosuppression, rejection, and arterial thrombosis, respectively. Fifty-two complications caused by IS agents were reported, and they were successfully managed medically or surgically. HAT recipients showed notable functional gains, but most complications resulted from the IS protocols.