Exploring Costimulatory Blockade-Based Immunologic Strategies in Transplantation: Are They a Promising Immunomodulatory Approach for Organ and Vascularized Composite Allotransplantation?

The field of transplantation, including the specialized area of vascularized composite allotransplantation (VCA), has been transformed since the first hand transplant in 1998. The major challenge in VCA comes from the need for life-long immunosuppressive therapy due to its non-vital nature and a high rate of systemic complications. Ongoing research is focused on immunosuppressive therapeutic strategies to avoid toxicity and promote donor-specific tolerance. This includes studying the balance between tolerance and effector mechanisms in immune modulation, particularly the role of costimulatory signals in T lymphocyte activation. Costimulatory signals during T cell activation can have either stimulatory or inhibitory effects. Interfering with T cell activation through costimulation blockade strategies shows potential in avoiding rejection and prolonging the survival of transplanted organs. This review paper aims to summarize current data on the immunologic role of costimulatory blockade in the field of transplantation. It focuses on strategies that can be applied in vascularized composite allotransplantation, offering insights into novel methods for enhancing the success and safety of these procedures.

The Flower Petal Training System in Microsurgery: Validation of a Training Model Using a Randomized Controlled Trial.

INTRODUCTION: Despite hundreds of training models for microsurgery being available in the literature, very few of them are scientifically validated. We chose to validate our low-fidelity training model on flower petals by comparing it head-to-head with a moderate fidelity training model, the anastomosis on chicken leg femoral artery. MATERIALS AND METHODS: A total of 16 participants of different levels of expertise were randomized into 2 groups, 1 training on flower petals and 1 on chicken leg femoral arteries. The groups were evaluated on performing a rat femoral artery anastomosis using the validated Stanford Microsurgical Assessment (SMaRT) Scale. The Mann-Whitney U test was used to check for statistically significant differences between the groups. The flower petal sutures were also evaluated and Pearson correlation was used to check for associations between better petal anastomosis scores and better final SMaRT results. RESULTS: After 6 weeks of flower petal training, microsurgical trainees had significantly better overall SMaRT scores than trainees using chicken leg training, better fine tissue feeling, and better scores in knot tying. The anastomosis times for the rat femoral arteries did not differ between the 2 groups. Good scores for flower petals strongly correlated with a better SMaRT score for the anastomosis. The number of rats used in training reduced after the implementation of this model in continuous training. CONCLUSIONS: The flower petal technique, despite being a low-fidelity model, shows superiority in developing fine tissue feeling and improved knot tying in microsurgery beginners and intermediate level practitioners adding this training model to their program. Further research needs to establish if the improvements also apply to already seasoned microsurgeons and whether the petal score has predictive value for future clinical application.

The hidden cause of chronic finger pain: Glomus Tumor - A Case Report.

Glomus tumors are frequently associated with pain, tenderness and cold sensitivity. We report the diagnosis and successful surgical management of a case of a classic glomus tumor in a young woman. The clinical diagnosis was made on the basis of medical history and MRI findings. The lesion was excised via a dorsolateral subungual approach, leading to the complete resolution of symptoms. Histology confirmed the lesion to be a glomus tumor. Glomus tumors are painful subungual lesions. They produce a throbbing or lancinating local discomfort, cold-sensitivity, and severe pain following minor trauma. The diagnosis is confirmed by histology, but the clinical diagnosis is highly suggestive. Complete excision will usually relieve pain. Recurrence is common following incomplete resection.

The interdisciplinary approach of an aggressive giant cell tumor of bone complicated with a fracture of the distal femur.

Giant cell tumor of bone (GCTB) represents one of the commonest bone tumors encountered by an orthopedic surgeon. The giant-cell tumor is generally classified as benign but the fast growing rhythm and the aggressive soft-tissue invasion may in some cases demonstrate a malign potential of the tumor. We present the case of an aggressive giant cell tumor in a young patient that was first diagnosed in our emergency department with a fracture of the distal femur after a low energy trauma. With further examinations, we discovered that the tumor was invading the both femoral condyles and was vascularized by three major arterial pedicles. The onset of his problems was the femoral fracture and the changes on the major vessels, muscles and nerves. After an interdisciplinary approach of the patient and a meticulous preoperative planning, we decided to make an extensive total resection of the tumor followed by a complex reconstruction surgery for the bone. A very stable fixation of a vascularized graft allowed the bone to heal even if the surrounded soft-tissue was almost completely invaded by the tumor and removed during the excision. The follow-up of this case demonstrated that using an interdisciplinary approach of the patient with the Plastic Surgery team, we manage to remove the tumor within oncological limits and achieved bone healing with good stability of the distal femur.

Delayed venous repair for distal phalanx replantation.

BACKGROUND: Vein anastomosis is the most important factor determining the success in the replantation of distal phalanx amputations. It is very difficult to find the collapsed veins and to perform vein anastomosis immediately after arterial repair. We have chosen to delay the vein repair between 30 minutes and 1 hour to give time to the veins to expand to a more reasonable diameter for repair. AIM: The purpose of the study was to show that the delayed venous method provides a higher rate of success in distal phalanx replantations and does not require the use of specialized techniques. METHODS: The delayed venous method for vein anastomosis was used for the past 2 years. This surgical procedure includes initial arterial anastomosis, delayed expansion of the vein, and subsequent vein anastomosis after 30 mins of waiting. RESULTS: The delayed method was used in eight cases. Expansion of veins up to 1 mm or more resulted in a high success rate (75%). In contrast, the success rate for distal phalanx replantation is extremely low in other techniques because of the difficulty of vein finding and anastomosis. CONCLUSION: The delayed venous method allows easier anastomosis of the subdermal veins of the distal phalanx. Therefore, it is a useful operative technique for treatment of amputated distal phalanx amputation.

Combined procedure of vascularized bone marrow transplantation and mesenchymal stem cells graft - an effective solution for rapid hematopoietic reconstitution and prevention of graft-versus-host disease.

Hematopoietic stem cell transplantation (HSCT) is a a standard therapeutic option for several diseases. The success of the procedure depends on quality and quantity of transplanted cells and on stromal capacity to create an optimal microenvironment, that supports survival and development of the hematopoietic elements. Conditions associated with stromal dysfunction lead to slower/insufficient engraftment and/or immune reconstitution. A possible solution to this problem is to realize a combined graft of hematopoietic stem cells along with the medular stroma in the form of vascularized bone marrow transplant (VBMT). Another major drawback of HSCT is the risk of graft versus host disease (GVHD). Recently, mesenchymal stromal cells (MSC) have demonstrated the capacity to down-regulate alloreactive T-cell and to enhance the engraftment. Cotransplantation of MSC could be a therapeutic option for a better engraftment and GVHD prevention.

Training program and learning curve in experimental microsurgery during the residency in plastic surgery.

This article presents a comparison of microsurgical training of groups with different background. A protocol based on the rat femoral arterial anastomoses was used to provide an objective representation of the microsurgical skills progress. The performance is assessed by consistent (x4) patency of a standardized anastomosis. Three groups of beginner residents with progressive microsurgical experience and one group of experienced surgeons were observed. The patency curve of the beginner-groups was as an abrupt learning curve, and then a plateau was reached. There was no statistically significant difference in the patency rate between the beginner-groups after their first 32 anastomoses. No statistically significant difference was noted when the patency of the advanced group was compared with beginner-groups after different numbers of anastomoses (inverse proportional with their training experience). A slight or a plateau learning curve was found among the experienced group. The learning curve is a useful adjunct in the assessment of training.