Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation.

The role of anti-HLA antibodies in transplant rejection is well-known but the injury associated with non-HLA antibodies is now widely discussed. The aim of our study was to investigate a role of non-HLA antibodies in hand allografts rejection. The study was performed on six patients after hand transplantation. The control group consisted of: 12 kidney transplant recipients and 12 healthy volunteers. The following non-HLA antibodies were tested: antibody against angiotensin II type 1 receptor (AT1R-Ab), antibody against endothelin-1 type-A-receptor (ETAR-Ab), antibody against protease-activated receptor 1 (PAR-1-Ab) and anti-VEGF-A antibody (VEGF-A-Ab). Chosen proinflammatory cytokines (Il-1, IL-6, IFNγ) were used to evaluate the post-transplant humoral response. Laboratory markers of endothelial activation (VEGF, sICAM, vWF) were used to assess potential vasculopathy. The patient with the highest number of acute rejections had both positive non-HLA antibodies: AT1R-Ab and ETAR-Ab. The same patient had the highest VEGF-A-Ab and very high PAR1-Ab. All patients after hand transplantation had high levels of laboratory markers of endothelial activation. The existence of non-HLA antibodies together with multiple acute rejections observed in patient after hand transplantation should stimulate to look for potential role of non-HLA antibodies in humoral injury in vascular composite allotransplantation.

Three-year (2017-2019) activity report of the Replantation Service for hand amputations in Poland.

This article summarises activity of the Replantation Service for hand amputations in Poland in years 2017-2019. Over this period a total of 551 cases of total and subtotal amputations as well as other complex injuries to the hand were referred to the referenced centres. Of these, 330 referrals were accepted and 221 rejected, for various reasons. Among these accepted, there were 165 total (50%) and 131 subtotal (40%) amputations; 34 patients (10%) had other severe hand injuries. Vast majority of the patients constituted young and middle-age males. The most common was amputation of several digits and thumbs - a total of 251 cases (76%), followed by transmetacarpal - 30 (9%), forearm - 23 (7%) and wrist - 20 (6%) amputations. Replantation of amputated extremity was performed in 138 patients (42%), revascularization in 98 (30%) and in 45 (14%) primary repair of the complex injuries. In 26 cases (8%), coverage of tissue defects was performed, and in 23 (7%) primary terminalization. Survival rate was of a mean of 65% for replantations and 85% for revascularizations. Comparing to the previously reported period 2013-2017, the number of treated patients was similar, but structure of injuries differed: number of digital amputations increased (of 22 cases), whereas number of proximal amputations (hand, forearm and arm) significantly dropped (of 50 cases). The importance of Replantation Service, an informal structure, in saving limbs of severely mutilated patients was emphasised.

Abnormal Nailfold Capillaries in Patients after Hand Transplantation.

BACKGROUND: The development of graft vasculopathy may play a role in the long-term deterioration of hand grafts. The aim of study was to examine the patterns of the nailfold capillaries in hand transplant recipients. METHODS: the study was performed on six patients who received hand transplantation. To normalize for the effect of immunosuppression an age- and sex-matched group of 12 patients with active kidney transplant was selected. As an additional control group, 12 healthy volunteers were recruited. Nailfold videocapillaroscopy was performed in all participants. Additionally, serum concentrations of vascular endothelial growth factor (VEGF) were measured. RESULTS: Videocapillaroscopic examination of the hand allografts revealed significant abnormalities: including capillary disorganization and microhaemorrhages. The number of capillaries was reduced, the vessels were enlarged and branched. Surprisingly, similar, albeit slightly less pronounced, changes were seen in the nailfolds of healthy hands of the limb transplant recipients. In kidney transplant recipients the capillaroscopic pattern was general normal and comparable to healthy individuals. Moreover, serum concentrations of VEGF in all participants correlated with average capillary diameter in capillaroscopy. CONCLUSIONS: in hand transplant recipients advanced microvascular abnormalities are found in nailfold capillaroscopic pattern in both transplanted and own extremities connected with elevated levels of VEGF.

Vascularized composite allotransplantation - a Council of Europe position paper.

After more than 120 hand-upper extremity and 37 face transplant procedures performed worldwide, vascularized composite allotransplantation (VCA) now falls under the scope of organ transplant legislation in Europe and the United States. While in the USA, VCA has been considered as standard care since 2014, VCA in Europe is still performed through clinical research trials, except in United Kingdom. However, after two decades of favourable experience with upper extremity transplantation (UET), professionals in Europe are proposing hand allotransplantation as "controlled standard" care, as opposed to face transplantation (FT), which is still a challenging activity. The European Committee on Organ Transplantation (CD-P-TO) has elaborated a position paper to provide recommendations concerning regulatory aspects for UET and FT. It is aimed at Health Authorities in charge of the oversight - and coordination - of organ donation and transplantation, and at professional groups to help them manage such complex and costly programs dedicated to properly selected patients.

Three-year (2014-2016) activity report of the Replantation Service for hand amputations in Poland.

The paper summarizes 32 months (January 2014 - August 2016) of activity of the Replantation Service for hand amputation in Poland. Over this period a total of 568 cases of total and subtotal amputations as well as other complex injuries to the hand were referred. Of these, 354 referrals (62%) were accepted and 214 (38%) rejected. Among accepted, there were 167 total (47%) and 142 subtotal (40%) amputations; 45 patients (13%) had other severe hand injuries. Vast majority of the patients constituted males aged a mean of 39 years. The most common injury was amputation of several digits in one patient, and thumb amputation - a total of 229 cases (65%), followed by transmetacarpal and wrist amputations - 92 (30%) and forearm/arm amputations - 33 cases (9%). Replantation of amputated extremity was performed in 141 patients (40%), revascularization in 145 (41%) and in 29 (8%) primary repair of the complex injuries. In 27 cases (8%), a coverage of the tissue defects, and in 12 (3%) primary terminalization was performed. Survival rate was of 78% for replantation and revascularization. Comparing to the period 2010-2012, an increase in number of treated patients (of n=64 cases), in number of amputations (of 96 cases) and in number of amputated digits (of 88 cases) were noted. The activity report shows importance of Replantation Service, an informal structure, in saving limbs of severely mutilated patients.

Immune activation- and regulation-related patterns in stable hand transplant recipients.

We assessed cell subsets and expression of a set of genes related to the T-cell populations in peripheral blood mononuclear cells to elucidate whether immune status of stable hand transplant recipients (HTx) differs from stable kidney transplant recipients (KTx). The study was conducted on five HTx 4.8 ± 1.7 years after transplantation and 30 stable KTx 7.9 ± 2.4 years after transplantation as well as 18 healthy volunteers. The research involved PBMC gene expression analysis of CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGF-B, and TNF-A genes on a custom-designed low-density array (TaqMan) as well as flow cytometry assessment of lymphocyte subpopulations. HTx presented significantly increased expression of immunomodulatory genes (TNF, IL10, GITR, and PDCD1) compared to KTx and controls. HTx revealed a proinflammatory molecular pattern with higher expression of NOTCH and CD8 compared to KTx and controls. KTx showed a reduced level of regulatory T cells compared to controls and HTx. Both HTx and KTx presented an increased number of CD8+ and CD8+ CD28- T cells compared to controls. Stable hand transplant recipients exhibit persistent immune activation with rejection-related gene expression pattern counterbalanced by secondary induction of regulatory mechanisms.

Functional and Psychosocial Outcomes of Hand Transplantation Compared with Prosthetic Fitting in Below-Elbow Amputees: A Multicenter Cohort Study.

BACKGROUND: Hand-transplantation and improvements in the field of prostheses opened new frontiers in restoring hand function in below-elbow amputees. Both concepts aim at restoring reliable hand function, however, the indications, advantages and limitations for each treatment must be carefully considered depending on level and extent of amputation. Here we report our findings of a multi-center cohort study comparing hand function and quality-of-life of people with transplanted versus prosthetic hands. METHODS: Hand function in amputees with either transplant or prostheses was tested with Action Research Arm Test (ARAT), Southampton Hand Assessment Procedure (SHAP) and the Disabilities of the Arm, Shoulder and Hand measure (DASH). Quality-of-life was compared with the Short-Form 36 (SF-36). RESULTS: Transplanted patients (n = 5) achieved a mean ARAT score of 40.86 ± 8.07 and an average SHAP score of 75.00 ± 11.06. Prosthetic patients (n = 7) achieved a mean ARAT score of 39.00 ± 3.61 and an average SHAP score of 75.43 ± 10.81. There was no significant difference between transplanted and prosthetic hands in ARAT, SHAP or DASH. While quality-of-life metrics were equivocal for four scales of the SF-36, transplanted patients reported significantly higher scores in "role-physical" (p = 0.006), "vitality" (p = 0.008), "role-emotional" (p = 0.035) and "mental-health" (p = 0.003). CONCLUSIONS: The indications for hand transplantation or prosthetic fitting in below-elbow amputees require careful consideration. As functional outcomes were not significantly different between groups, patient's best interests and the route of least harm should guide treatment. Due to the immunosuppressive side-effects, the indication for allotransplantation must still be restrictive, the best being bilateral amputees.

The Physical and Psychosocial Benefits of Upper-Limb Transplantation: A Case Series of 5 Polish Patients.

BACKGROUND: Although upper-limb transplantation is not a life-saving procedure, every year more and more patients are ready to undergo this surgery. Conventional methods of treatment performed earlier have not brought the expected functional and aesthetic results. Patients who have received upper-limb transplantation (HTx) enjoy, in addition to the physical benefits associated with good functional effect, numerous benefits of a psychological and social nature. Investigation of these benefits was the aim of this interdisciplinary research. CASE REPORT: The wide spectrum of physical, psychological, and social benefits derived by recipients of limb transplantation include: improved physical fitness, recovery of the complete body form, corporeal well-being, enhanced self-esteem, recovery of self-confidence, a stable feeling of personal and social identity, higher integration of the body with performed social roles, greater confidence in the ability to act and have control over life, a feeling of greater security, the ability to return to work, restoration of social position, and positive personality changes. CONCLUSIONS: Potential benefits which may be derived by future upper limb recipients are manifested in the good functional effect of the transplantation, enhanced life satisfaction, and better functioning in society. It does not mean, however, restoration of 100% of fitness or absolutely problem-free functioning in everyday life, which is extremely important in the context of prevention of possible disappointment to future limb recipients.

Assessment of vascular function of hand allografts.

BACKGROUND: Insufficiency of blood vessels supplying a limb allograft may lead to loss of the extremity. Thus, a regular evaluation of perfusion of transplants seems a reasonable approach. The purpose of the present study was assessment of allograft perfusion by means of non-invasive methods. MATERIAL/METHODS: Six hand allografts transplanted in 5 patients were included in the study group. The transplant procedure occurred on average 45 months before. The study group comprised 2 allografts at forearm level, 2 transplants of the arm, and 1 bilateral transplant of the forearm. Parameters of blood flow using Doppler ultrasonography, impedance plethysmography, Doppler measurement of segmental pressures, optical pulse oscillography (OPO), and thermography were performed in all participants. RESULTS: DUS revealed increased resistive index in ulnar arteries of transplant hands compared to native hands and an altered blood supply was confirmed by IP. Flow-mediated dilatation within the transplanted extremity was abnormal in most patients and was inversely correlated with number of episodes of acute rejection. Analysis of oscillographic spectrum revealed flattening of the dicrotic notch in transplant hands. A tendency for lower temperature of the skin of transplanted hands compared to native extremities was also observed. CONCLUSIONS: In asymptomatic patients after limb transplantation, non-invasive methods disclosed discreet abnormalities of graft perfusion. Thus, regular measurement of perfusion parameters using these methods appears to be a promising approach to detect early and potentially reversible disturbances of blood supply. Further observational studies are required to determine its clinical significance.

Humoral immunity in hand transplantation: anti-HLA and non-HLA response.

UNLABELLED: Antibodies against donor's HLA antigens and B cell activity are recognized modulators of immune response to allograft. The role of both anti-HLA and non-HLA antibodies is understood in solid organ transplantation, but has not been addressed in composite tissue allografts. AIM: We decided to evaluate the presence and role of anti-HLA and non-HLA antibodies after hand transplantation. METHODS: We assayed anti-HLA and non-HLA antibodies in 5 consecutive hand transplant patients. The presence of anti-HLA antibodies was tested by flow-PRA method (One Lambda). Non-HLA antibodies were defined as anti-endothelial cell (AECA), anti-angiotensin II type 1 receptor (anti-AT1R), anti-endothelin receptor antibodies (anti-ETAR). RESULTS: Anti-HLA antibodies were present in 1 patient in class I and in another one in class II. Both patients developed one episode of acute rejection. AECA were present in only one recipient with borderline activity. Both anti-AT1R and Anti-ETAR were found strongly positive in one patient who repeatedly developed acute rejection episodes. CONCLUSION: The presence of non-HLA antibodies (anti-AT1R and anti-ETAR) and the occurrence of multiple rejection episodes found in one patient here require further investigation into a possible association and role of humoral immunity in composite tissue rejection.

New concept of scapholunate dissociation treatment and novel modification of Brunelli procedure - anatomical study.

BACKGROUNDS: This paper describes a novel method in treatment of scapholunate dissociation accompanied with rotatory subluxation of the scaphoid. The idea of this method is to create a kind of axial lever that can fully reconstruct anatomical relationship between the scaphoid and the lunate, with no involvement of extrinsic ligaments, and with simultaneous restriction of pathological alignment of the scaphoid. Based on this technique, we have also proposed a new modification of Brunelli procedure in scapholunate dissociation with rotatory subluxation of the scaphoid and dorsal intercalated segmental instability. METHODS: At the initial stage of the study, 20 human wrists fixed in Ethanol were used, followed by 12 fresh human wrists used in part two. The first stage included functional, biomechanical and strength tests carried out by means of a 5 kg load and intended to find the most anatomical and durable treatment method. The second stage involved testing the proposed methods on fresh cadaver wrists. RESULTS: We have discovered that the new method is able to recreate anatomical forces and properties of scapholunate ligament; what's more, it can also prevent rotatory subluxation of the scaphoid. The performed strength tests have proven that it is possible to treat scapholunate instability also in case of dorsal intercalated segmental instability. CONCLUSIONS: We highly recommend using both the new technique and the new modification of Brunelli procedure for treatment of scapholunate dissociation in both dynamic and static instabilities.

Acute compartment syndrome after open forearm fracture--scale of the problem and case report.

Acute compartment syndrome is caused due to a sudden increase in the tissue pressure in a given fascial compartment. Missed and undiagnosed or not treated in time can lead to irreversible damage to limb muscles and nerves due to ischemia mechanism. This paper presents a case of a patient with an open forearm fracture treated conservatively in plaster.

"Dangerous" anatomic varieties of recurrent motor branch of median nerve.

UNLABELLED: Carpal tunnel release became one of the most common operations in the field of hand surgery. Many controversies has been made about frequency of the so-called dangerous variations of motor branch of the median nerve. Knowledge of all the anatomical variations motor branches is the duty of every surgeon dealing with the subject. The aim of the study was to present the incidence of dangerous variants of median nerve motor branch in the carpal tunnel based on both clinical experience and anatomical studies performed on 20 cadaver wrists. MATERIAL AND METHODS: Between 2006-2012 during minimally open carpal tunnel release we made photographic documentation of all visible dangerous varieties of recurrent motor branches of the median nerve. We also studied 20 cadaver wrists in the Department of Anatomy Medical University in Wroclaw. RESULTS: Dangerous varieties of the motor branch of median nerve was found in three clinical cases and in one cadaver wrist. Also In one wrist we found one regular branche, which, however, has atypical two separate branches supplying the thenar muscles. CONCLUSIONS: Dangerous varieties of the motor branch of median nerve occur very rare in the population, but does not release from the fact that in each case special attention must be given.We also conclude that, at the minimally open carpal tunnel release procedure, the transverse carpal ligament should be released rather from the line of radial border of the 4th finger to minimize the risk of injury to the recurrent motor branch of median nerve.

Post-traumatic thumb reconstruction with radial forearm flap.

The study described a case of a 37-year-old patient, who had undergone avulsion amputation of the thumb, and was subject to a primary thumb reconstruction by means of thumb reconstruction with radial forearm flap, with the use of osseous fragments of the amputated thumb parts.

Treatment possibilities of reverse-flow sural flap in covering the defects of lower extremities.

UNLABELLED: Soft tissue defects of the lower extremity pose an important surgical challenge, often because of inviability of primary covering. Therapeutic modalities of choice comprise of local perforator flaps, as well as of free flaps created with the use of microsurgical skills. However, these methods cannot be applied in patients with important comorbidities, and it is in such cases where the reverse sural flap proves to be the best solution. THE AIM OF THE STUDY: To present the results of treating lower extremity defects with various modifications of the reverse sural flap. MATERIAL AND METHODS: Sixteen patients, males aged 17-56 years, were operated on from 2007 to 2013. Diabetes with multiple complications, disseminated atheromatosis, and extensive soft tissue trauma involving the arteries crucial for microsurgica anastomoses were the most common reason disqualifying from the free and perforator-based flap techniques. RESULTS: All of the patients achieved very good results; in two cases distal and marginal flap necrosis was observed which, once exiced, covered with granulation, and was successfully covered with a partial-thickness skin graft. CONCLUSIONS: The reverse sural flap, technically easy, offers a viable, low-risk alternative to free and perforator-based flaps.

Surgical treatment of hemangiomas and arteriovenous malformations in upper extermity.

UNLABELLED: Hemangiomas belong to one of the most common type of tumors occurring in childhood. They are benign and often do not require any treatment, with the tendency to. frequently disappearing spontaneously at the age of 5-7 years. The tumors usually develop in the head and neck area, whereas vascular malformations (AVMs) are rare congenital anomalies, which may occur anywhere. In upper limb, they may amount to 30-60% of cases. It is common for these changes not to require any surgical treatment. In case they do, the main indications for such treatment of upper limb AVMs may be as follows: signs of compression of the peripheral nerves, limited mobility of the fingers because of the tumor, which entails difficulties in the functioning of the whole arm, pain and aesthetic considerations. AIM OF THE STUDY: was to present the results of surgical treatment of vascular tumors (hemangiomas and AVMs) in the upper limb that was applied in our department, as well as a broader discussion on epidemiology, diagnosis, and treatment of these changes. MATERIAL AND METHODS: In 2003-2011 period we treated 11 patients aged 24-39, suffering from vascular tumors (hemangiomas / vascular malformations) in the upper limb; the group included 3 men and 8 women. In this group we diagnosed 2 cases with arm hemangiomas, 2 cases of intramuscular hemangiomas of the forearm, 2 cases of hemangiomas in metacarpal area, 2 cases of AVMs of the finger and metacarpal area, and 4 cases of isolated vascular malformations (mainly arteriovenous malformations) of the fingers. All preparations were examined histologically. RESULTS: No complications or recurrence were found in 7 cases, recurrences of AVMs were observed in 4 patients with finger changes. In one patient with AVMs of the index finger, we observed a treble recurrence, which severely impaired functioning of his hand. We eventually suggested to him the finger amputation, to which the patient agreed. CONCLUSIONS: Upper extremity is a rare location of hemangiomas and other vascular malformations requiring surgery. hemangiomas are more common in women, and the occurrence of AVMs in both males and females is similar. Surgical treatment of hemangiomas and AVMs of the upper extremities is doubtlessly an arduous task, which calls for great microsurgical skills.

Standardizing skin biopsy sampling to assess rejection in vascularized composite allotransplantation.

Over 70 hands and 20 faces have been transplanted during the past 13 yr, which have shown good to excellent functional and esthetic outcomes. However, (skin) rejection episodes complicate the post-operative courses of hand and face transplant recipients and are still a major obstacle to overcome after reconstructive allotransplantation. This article summarizes all relevant information on the skin component and rejection of a vascularized composite allograft. As more and more centers plan to implement a vascularized composite allotransplantation (VCA) program, we further develop guidelines and recommendations on collection and processing of skin biopsies from hand and face allograft recipients. This will help to standardize post-operative monitoring, avoid pitfalls for those new in the field and facilitate comparison of data on VCA between centers.

Radiological and anatomical study to investigate possibility of relationship between scaphoid fracture and lunate morphology.

BACKGROUND: A connection between lunate type has been described for medical conditions like Kienbock's disease as well as for wrist osteoarthritis, e.g. STT osteoarthritis. Aim of the Study to investigate the possibility of a relationship between lunate type and the type of wrist injury mainly localised to the scaphoid bone. MATERIAL AND METHODS: 394 PA and lateral radiographs of the wrist (n = 394) were subjected to a detailed assessment by two independent surgeons. The X-rays were selected and analyzed from a computer and archive database run by St. Hedwig Hospital in Trzebnica, from the beginning of January 2011 till the end of December 2012. Most of the X-rays (69%) were obtained from citizens of Trzebnica District. In addition, detailed anatomical studies of the wrist bones were carried out on 20 human preparations fixed in ethanol. RESULTS: Lunate type I was found in 288 wrist radiographs (73%) and type II in the remaining 106 photos (27%). Various types of wrist injuries were diagnosed in 129 cases. These were mainly distal radius fractures, scaphoid fractures and isolated scapholunate instability. There exists a statistically confirmed relationship between scaphoid fracture and lunate type II as well as a connection between lunate type and gender. Anatomical examination of 20 wrists showed the presence of lunate type I in 11 cases and type I in 9 cases. CONCLUSION: 1. Lunate type II is more frequently encountered in men. 2. Scaphoid fractures are more common with lunate type II. 3. The joint surface for the hamate in lunate type II is 2-7 mm in width. 4. The presence of another articular surface for the hamate in lunate type II may contribute to the formation of degenerative changes in the lunohamate joint.

Unsuccessful replantation of metacarpal hand after venous thrombosis--case report.

Trans-metacarpal hand replantation is one of the most complex and difficult procedures in the reconstructive microsurgery. As far as we know the arrangement of the palmar arterial network, the problem lies in the absence of accurate venous maps at the dorsum of the hand. The quality of venous circulation structure at the replanted hand determine the success of the surgery. In this paper we present a case of a failed replantation of a metacarpal hand after early thrombosis at the venous microcirculation system.

[An example of multi-stage reconstruction of a full-thickness abdominal wall defect]. / Przyklad wieloetapowej rekonstrukcji pelnej grubosci ubytku sciany jamy brzusznej.

Abdominal wall reconstruction is a highly complex procedure that may requires a multiple stages surgical operations. The aim of a such reconstruction is to close the abdominal wall defect and to create a support for the internal organs. It's a challenge for both general and reconstructive surgery. An incomplete thickness defects of the abdominal wall are so much easier to challenge than complete ones. Also the size of the primary defect determines the way and stages of the operation. Such defects can occur in necrotizing fasciitis of the abdominal wall, after abdominal walls tumors removal, in traffic accidents or after "open abdomen" procedures (acute severe pancreatitis). In this paper the authors present a case of 62-yo patient which was operated because of large intestine perforation with various complications of which the most serious was the abdominal wall defect.