10-Year single center experience in lower limb reconstruction with free muscle flaps - factors influencing complications in 266 consecutive cases.

The anatomy and technique of free muscle flaps - in particular gracilis flap and latissimus dorsi flap - in lower extremity reconstruction have been well described. There is a paucity of data on potential risk factors in larger patient series that affect the outcome. The objective of this study was to address this lack of knowledge by reporting outcomes and complications of free muscle flaps as a primary option in lower extremity reconstruction. From 2009 to 2020, a total of 253 consecutive patients with soft tissue defects of the lower limb from trauma, infection or malignancies underwent lower extremity reconstructive surgery with 266 free muscle flaps. Complications requiring revision surgery were noted in 36.1% of cases. Total flap loss occurred in 10.5% of cases. Patients requiring revision surgery were older, more likely to be female, more likely to be active smokers, and more likely to have a higher ASA score. Lower extremity reconstruction with free muscle flaps has a relevant complication rate that both patient and reconstructive surgeon need to be aware of. Prospective studies should try to further assess the factors affecting the outcome.

Adipose tissue-derived microvascular fragments promote lymphangiogenesis in a murine lymphedema model.

Chronic lymphedema after cancer treatment is common and there is still no cure for this disease. We herein investigated the lymphangiogenic capacity of adipose tissue-derived microvascular fragments (MVF), which contain stem cells and lymphatic vessel fragments. Secondary lymphedema was induced in the hindlimbs of C57BL/6J mice. Green fluorescence protein (GFP)+ MVF were isolated from transgenic C57BL/6Tg (CAG-EGFP)1Osb/J mice, suspended in collagen hydrogel, and injected in the lymphadenectomy defect of wild-type animals. This crossover model allowed the detection of MVF-derived blood and lymphatic vessels after transplantation. The MVF group was compared with animals receiving collagen hydrogel only or a sham intervention. Lymphangiogenic effects were analyzed using volumetry, magnetic resonance (MR) lymphography, histology, and immunohistochemistry. MVF injection resulted in reduced hindlimb volumes when compared to non-treated controls. MR lymphography revealed lymphatic regeneration with reduced dermal backflow after MVF treatment. Finally, MVF transplantation promoted popliteal angiogenesis and lymphangiogenesis associated with a significantly increased microvessel and lymphatic vessel density. These findings indicate that MVF transplantation represents a promising approach to induce therapeutic lymphangiogenesis.

Intraneural fibrosis and loss of microvascular architecture - Key findings investigating failed human nerve allografts.

BACKGROUND: Processed nerve allografts are increasingly used in clinical nerve reconstruction with promising results. However, allograft failure has been reported, leading to chronic pain and persistent loss of function. In the present work, we performed a histological and immunohistochemical analysis of two failed allograft reconstructions of a sensory human nerve one year after primary surgery. METHODS: Two patients with a superficial radial nerve injury underwent nerve reconstruction with processed nerve allografts. The clinical follow-up was complicated by severe neuropathic pain and absent sensory reinnervation. Consequently, the failed allografts were excised with subsequent histological and immunohistochemical examinations. For that purpose, the collagen content and neurofilament network as well as the blood and lymphatic vasculature were analysed in the center of the specimens. RESULTS: Histology revealed increased fibrosis, fatty degeneration, and disorganised proliferation of nerve fibres. Moreover, the microvascular network within the allografts was characterised by increased numbers of microvessels, whereas no difference was found concerning the lymphatic vasculature. CONCLUSION: The herein presented histological and immunohistochemical findings indicate that the failure of human allografts is associated with loss of the physiological microvascular architecture. Future studies elucidating the complex interplay of angiogenesis, lymphangiogenesis and axonal regeneration are required to better understand the mechanisms of human allograft failure.

Basic science approaches to common hand surgery problems.

The field of hand surgery is constantly evolving to meet challenges of populations with increasing age and higher demands for active living. While our surgical care has improved over the last decades, it seems that future major improvement in outcomes of clinical treatment will come through advances in biologics and the translation of major discoveries in basic science. This article aims to provide an update on where basic science solutions may answer some of the most critical issues in hand surgery, with a focus on augmentation of tissue repair.

[Pain In the Thumb and Other Fingers]. / Schmerzen im Daumen und anderen Fingern.

Pain In the Thumb and Other Fingers Abstract. As the population ages, symptoms of osteoarthritis in the hand are seen with increasing frequency. It can lead to substantial pain, physical disability and impair the patient's capacity to work in a population with an increasing retirement age. This article gives an overview about the most prevalent forms of osteoarthritis in the hand, its diagnosis and current treatment options, stressing that the multimodal form of therapy is the most effective.

[The Painful Wrist]. / Das schmerzhafte Handgelenk.

The Painful Wrist Abstract. Wrist pain is a problem that can significantly limit patients in their daily activities. The causes are manifold, and treatment is often challenging. A systematic approach is therefore helpful in working up the correct diagnosis. This article aims to demonstrate a straightforward approach to the evaluation of wrist pain in adults.

[Tendinopathies - Common Diagnoses in Hand Surgery]. / Tendinopathien ­ häufige Diagnosen in der Handchirurgie.

Tendinopathies - Common Diagnoses in Hand Surgery Abstract. Tendinopathies are among the most frequent reasons for consulting a hand surgeon. The diagnosis can usually be made clinically. A supplementary ultrasound examination helps to visualize the pathology. Most of these diseases respond to non-surgical treatment. If surgical treatment is necessary, it can usually be performed as an outpatient procedure under local anesthesia. This article provides an overview of the most common tendinopathies of the hand and wrist, their diagnosis and treatment.

[Neuropathic Pain - Differential Diagnosis and Treatment from the Hand Surgeon's Perspective]. / Neuropathische Schmerzen ­ Handchirurgische Differenzialdiagnose und Therapie.

Neuropathic Pain - Differential Diagnosis and Treatment from the Hand Surgeon's Perspective Abstract. Neuropathic pain of the wrist and hand can be caused by a multitude of pathologies, such as trauma, iatrogenic damage, local peripheral nerve compression, nerve tumors and systemic diseases. Neuropathic pain can lead to chronification and disability, severely affecting the patients' quality of life and the ability to work. A precise diagnosis is the key to an adequate therapy with satisfactory functional results. An interdisciplinary and multimodal approach is a prerequisite when treating neuropathic pain. This review article provides an insight into the diagnosis and therapy of pathologies associated with neuropathic pain of the wrist and hand.

Fluorescence angiography-assisted debridement of critically perfused glabrous skin in degloving foot injuries: Two case reports.

RATIONALE: Degloving foot injuries are challenging to treat and associated with life-long sequelae for patients. An appropriate debridement of ischemic soft tissues with maximal preservation of glabrous skin is key during the reconstruction of these injuries. Indocyanine green (ICG) fluorescence angiography is an established technique for the intraoperative evaluation of tissue perfusion. PATIENT CONCERNS: Two patients sustained complex foot injuries in traffic accidents, including multiple fracture dislocations and extensive degloving of the plantar skin. DIAGNOSIS: Clinical inspection revealed significant degloving of the glabrous skin in both patients. INTERVENTIONS: After fracture fixation, ICG fluorescence angiography-assisted debridement with immediate latissimus dorsi free flap reconstruction was performed. OUTCOMES: In both cases, this technique allowed a precise debridement with maximal preservation of the glabrous skin. The healing of the remaining glabrous skin was uneventful and the 6-month follow-up was characterized by stable soft tissues and satisfying ambulation. LESSONS: ICG fluorescence angiography is a safe, user-friendly, and quick procedure with minimal risks, expanding the armamentarium of the reconstructive surgeon. It is highly useful for the debridement of extensive plantar degloving injuries and may also help to minimize the number of procedures and the risk of infection.

Improvement of islet transplantation by the fusion of islet cells with functional blood vessels.

Pancreatic islet transplantation still represents a promising therapeutic strategy for curative treatment of type 1 diabetes mellitus. However, a limited number of organ donors and insufficient vascularization with islet engraftment failure restrict the successful transfer of this approach into clinical practice. To overcome these problems, we herein introduce a novel strategy for the generation of prevascularized islet organoids by the fusion of pancreatic islet cells with functional native microvessels. These insulin-secreting organoids exhibit a significantly higher angiogenic activity compared to freshly isolated islets, cultured islets, and non-prevascularized islet organoids. This is caused by paracrine signaling between the ß-cells and the microvessels, mediated by insulin binding to its corresponding receptor on endothelial cells. In vivo, the prevascularized islet organoids are rapidly blood-perfused after transplantation by the interconnection of their autochthonous microvasculature with surrounding blood vessels. As a consequence, a lower number of islet grafts are required to restore normoglycemia in diabetic mice. Thus, prevascularized islet organoids may be used to improve the success rates of clinical islet transplantation.

Intramedullary compression screw fixation of metacarpal and phalangeal fractures.

The intramedullary headless compression screw (IMCS) technique represents a reliable alternative to percutaneous Kirschner-wire and plate fixation with minimal complications.Transverse fractures of the metacarpal shaft represent a good indication for this technique. Non-comminuted subcapital and short oblique fractures can also be treated with IMCS.This technique should not be used in the presence of an open epiphysis, infection and, most of all, in subchondral fractures, because of the lack of purchase for the head of the screw.A double screw construct is recommended for comminuted subcapital fractures of the metacarpal to avoid metacarpal shortening. IMCS can even be applied for peri-articular fractures of the proximal third of the phalanx and in some multi-fragmentary proximal and middle phalangeal fractures.Usually the intramedullary screws are not removed. The main indications for screw removal are joint protrusion, infection and screw breakage after new fracture. Cite this article: EFORT Open Rev 2020;5:624-629. DOI: 10.1302/2058-5241.5.190068.

Short-term molecular and cellular effects of ischemia/reperfusion on vascularized lymph node flaps in rats.

Vascularized lymph node (VLN) transfer is an emerging strategy to re-establish lymphatic drainage in chronic lymphedema. However, the biological processes underlying lymph node integration remain elusive. This study introduces an experimental approach facilitating the analysis of short-term molecular and cellular effects of ischemia/reperfusion on VLN flaps. Lymph node flaps were dissected pedicled on the lateral thoracic vessels in 44 Lewis rats. VLN flaps were exposed to 45 or 120 minutes ischemia by in situ clamping of the vascular pedicle with subsequent reperfusion for 24 hours. Flaps not exposed to ischemia/reperfusion served as controls. Lymph nodes and the perinodal adipose tissue were separately analyzed by Western blot for the expression of lymphangiogenic and angiogenic growth factors. Moreover, morphology, microvessel density, proliferation, apoptosis and immune cell infiltration of VLN flaps were further assessed by histology and immunohistochemistry. Ischemia for 120 minutes was associated with a markedly reduced cellularity of lymph nodes but not of the perinodal adipose tissue. In line with this, ischemic lymph nodes exhibited a significantly lower microvessel density and an increased expression of VEGF-D and VEGF-A. However, VEGF-C expression was not upregulated. In contrast, analyses of the perinodal adipose tissue revealed a more subtle decrease of microvessel density, while only the expression of VEGF-D was increased. Moreover, after 120 minutes ischemia, lymph nodes but not the perinodal adipose tissue exhibited significantly higher numbers of proliferating and apoptotic cells as well as infiltrated macrophages and neutrophilic granulocytes compared with non-ischemic flaps. Taken together, lymph nodes of VLN flaps are highly susceptible to ischemia/reperfusion injury. In contrast, the perinodal adipose tissue is less prone to ischemia/reperfusion injury.

Increased levels of VEGF-C and macrophage infiltration in lipedema patients without changes in lymphatic vascular morphology.

Lipedema is a chronic adipose tissue disorder characterized by the disproportional subcutaneous deposition of fat and is commonly misdiagnosed as lymphedema or obesity. The molecular determinants of the lipedema remain largely unknown and only speculations exist regarding the lymphatic system involvement. The aim of the present study is to characterize the lymphatic vascular involvement in established lipedema. The histological and molecular characterization was conducted on anatomically-matched skin and fat biopsies as well as serum samples from eleven lipedema and ten BMI-matched healthy patients. Increased systemic levels of vascular endothelial growth factor (VEGF)-C (P = 0.02) were identified in the serum of lipedema patients. Surprisingly, despite the increased VEGF-C levels no morphological changes of the lymphatic vessels were observed. Importantly, expression analysis of lymphatic and blood vessel-related genes revealed a marked downregulation of Tie2 (P < 0.0001) and FLT4 (VEGFR-3) (P = 0.02) consistent with an increased macrophage infiltration (P = 0.009), without changes in the expression of other lymphatic markers. Interestingly, a distinct local cytokine milieu, with decreased VEGF-A (P = 0.04) and VEGF-D (P = 0.02) expression was identified. No apparent lymphatic anomaly underlies lipedema, providing evidence for the different disease nature in comparison to lymphedema. The changes in the lymphatic-related cytokine milieu might be related to a modified vascular permeability developed secondarily to lipedema progression.

Adipose tissue and the vascularization of biomaterials: Stem cells, microvascular fragments and nanofat-a review.

Tissue defects in the human body after trauma and injury require precise reconstruction to regain function. Hence, there is a great demand for clinically translatable approaches with materials that are both biocompatible and biodegradable. They should also be able to adequately integrate within the tissue through sufficient vascularization. Adipose tissue is abundant and easily accessible. It is a valuable tissue source in regenerative medicine and tissue engineering, especially with regard to its angiogenic potential. Derivatives of adipose tissue, such as microfat, nanofat, microvascular fragments, stromal vascular fraction and stem cells, are commonly used in research, but also clinically to enhance the vascularization of implants and grafts at defect sites. In plastic surgery, adipose tissue is harvested via liposuction and can be manipulated in three ways (macro-, micro- and nanofat) in the operating room, depending on its ultimate use. Whereas macro- and microfat are used as a filling material for soft tissue injuries, nanofat is an injectable viscous extract that primarily induces tissue remodeling because it is rich in growth factors and stem cells. In contrast to microfat that adds volume to a defect site, nanofat has the potential to be easily combined with scaffold materials due to its liquid and homogenous consistency and is particularly attractive for blood vessel formation. The same is true for microvascular fragments that are easily isolated from adipose tissue through collagenase digestion. In preclinical animal models, it has been convincingly shown that these vascular fragments inosculate with host vessels and subsequently accelerate scaffold perfusion and host tissue integration. Adipose tissue is also an ideal source of stem cells. It yields larger quantities of cells than any other source and is easier to access for both the patient and doctor compared with other sources such as bone marrow. They are often used for tissue regeneration in combination with biomaterials. Adipose-derived stem cells can be applied unmodified or as single cell suspensions. However, certain pretreatments, such as cultivation under hypoxic conditions or three-dimensional spheroids production, may provide substantial benefit with regard to subsequent vascularization in vivo due to induced growth factor production. In this narrative review, derivatives of adipose tissue and the vascularization of biomaterials are addressed in a comprehensive approach, including several sizes of derivatives, such as whole fat flaps for soft tissue engineering, nanofat or stem cells, their secretome and exosomes. Taken together, it can be concluded that adipose tissue and its fractions down to the molecular level promote, enhance and support vascularization of biomaterials. Therefore, there is a high potential of the individual fat component to be used in regenerative medicine.

Finger reconstruction with dorsal metacarpal artery perforator flaps and dorsal finger perforator flaps based on the dorsal branches of the palmar digital arteries - 40 consecutive cases.

Since the first description many variations of the dorsal metacarpal reverse island flap have been published but there is still uncertainty about which vascular component should be included for an optimal result. Therefore, it was the aim of this study to analyze vascular reliability and ischemic complications of dorsal metacarpal artery perforator (DMAP) flaps and dorsal finger perforator (DFP) flaps in our patient collective. We performed 40 of these flaps from the dorsum of hand and fingers for finger injuries. The choice of donor site was made according to the defect's location. Patients were analyzed with respect to flap necrosis, ischemic complications and achievement of overall reconstruction goals. In addition, we divided our patients in two groups, one group where we raised the flap from the dorsum of the proximal phalanx and a second one where the flaps were raised from the intermetacarpal space to identify complication rates based on the pedicles location. Of the 40 flaps, 36 survived completely. 4 partial necroses were observed in flaps transferred to more distal defects and in one flap that was used in a wrap-around technique for both dorsal and palmar proximal phalanx. These perforator flaps are a reliable method to cover finger defects and the dorsal metacarpal artery is not necessary for their survival, since the blood supply comes from perforating branches of the palmar vascular system. There is a clear trend for a higher complication rate in flaps raised from the dorsum of the fingers compared to the intermetacarpal space.

Flexor tendon grafts for pulley reconstruction - Morphological aspects.

BACKGROUND: Pulleys are crucial to convert flexor tendon excursion into angular motion at the metacarpophalangeal and interphalangeal joints. Loss of pulley function can lead to significant impairment of hand function and may require surgical reconstruction. This reconstruction can be achieved using different flexor tendons grafts, such as the intrasynovial flexor digitorum superficialis (FDS) or the extrasynovial palmaris longus (PL). However, there is limited knowledge on the micromorphology of human pulleys and the suitability of flexor tendon grafts for their reconstruction remains elusive. METHODS: In the present cadaver study A2 and A4 pulleys were compared with FDS and PL tendons by means of scanning electron microscopy (SEM), histology and immunohistochemistry. Surface morphology, core structure and vascularization of the specimens were analyzed. RESULTS: SEM imaging of the gliding surfaces revealed morphological differences between tendons and pulleys. Moreover, the core structure of FDS samples was characterized by bundles of individual collagen fibrils whereas PL tendons exhibited a less hierarchical microstructure. In contrast, pulleys consisted of lamellar sheets of densely packed collagen fibrils. Finally, immunohistochemical analyses revealed that the flexor tendons and pulleys contain similar numbers of CD31+ microvessels, indicating a comparable tissue vascularization. CONCLUSION: This study provides novel SEM and immunohistochemical insights into the micromorphology of human pulleys and flexor tendon grafts. Intrasynovial flexor tendons may be particularly suitable for pulley reconstruction and preserving the paratenon may be crucial for graft revascularization.

Intramedullary screw fixation for metacarpal shaft fractures: a biomechanical human cadaver study.

Intramedullary cannulated compression screws have been introduced for the fixation of unstable metacarpal fractures. In the present study, this technique was compared with dorsal compression plating to evaluate its biomechanical performance in stabilizing metacarpal shaft fractures. In a first set of experiments, the biomechanical characteristics of the screws were analysed in an artificial bone model. In subsequent experiments, midshaft osteotomies were performed in human cadaver metacarpals, followed by plating or intramedullary screw osteosynthesis. The metacarpals were tested to failure in cantilever bending, following a stepwise increasing cyclic loading protocol. We found a significantly lower load at failure and a significantly lower number of cycles to failure in the intramedullary screw group, but both methods offered sufficient stability under these loads. With reference to published loads on the metacarpals during use of the hand, we conclude that intramedullary osteosynthesis yields sufficient strength and stiffness for early active motion. A difference in its fixation stability is noted compared with plate fixation, which may not be clinically relevant.

Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF-2 in adipose tissue during endotoxemia.

Sepsis is a leading cause of death worldwide and recent studies have shown white adipose tissue (WAT) to be an important regulator in septic conditions. In the present study, the role of the inflammatory cytokine macrophage migration inhibitory factor (MIF) and its structural homolog D-dopachrome tautomerase (D-DT/MIF-2) were investigated in WAT in a murine endotoxemia model. Both MIF and MIF-2 levels were increased in the peritoneal fluid of LPS-challenged wild-type mice, yet, in visceral WAT, the proteins were differentially regulated, with elevated MIF but downregulated MIF-2 expression in adipocytes. Mif gene deletion polarized adipose tissue macrophages (ATM) toward an anti-inflammatory phenotype while Mif-2 gene knockout drove ATMs toward a pro-inflammatory phenotype and Mif-deficiency was found to increase fibroblast viability. Additionally, we observed the same differential regulation of these two MIF family proteins in human adipose tissue in septic vs healthy patients. Taken together, these data suggest an inverse relationship between adipocyte MIF and MIF-2 expression during systemic inflammation, with the downregulation of MIF-2 in fat tissue potentially increasing pro-inflammatory macrophage polarization to further drive adipose inflammation.

A potential role of lymphangiogenesis for peripheral nerve injury and regeneration.

Traumatic peripheral nerve injuries are common and socioeconomically highly relevant. Despite significant microsurgical advances, the results of surgical reconstruction are still far from optimal and the rate of life-long complications, such as impaired motor and sensory function or neuropathic pain, is high. Moreover, the regeneration of peripheral nerves is a complex and fragile process that is not yet completely understood. Hence, there is an urgent need to further elucidate the underlying biological mechanisms. Herein, we propose that the neural lymphatic vasculature and lymphangiogenesis play an essential role in both peripheral nerve injury and regeneration and discuss hypothetical mechanisms implementing the current literature. Finally, specific research approaches to test our hypothesis are introduced.