Transgenic Epidermal Cultures for Junctional Epidermolysis Bullosa - 5-Year Outcomes.

Inherited junctional epidermolysis bullosa is a severe genetic skin disease that leads to epidermal loss caused by structural and mechanical fragility of the integuments. There is no established cure for junctional epidermolysis bullosa. We previously reported that genetically corrected autologous epidermal cultures regenerated almost an entire, fully functional epidermis on a child who had a devastating form of junctional epidermolysis bullosa. We now report long-term clinical outcomes in this patient. (Funded by POR FESR 2014-2020 - Regione Emilia-Romagna and others.).

Benefits of an Adjustable Compression Garment System for the Reduction of Chronic Leg Oedema (ACROE Study).

OBJECTIVE: This study aimed to assess whether a specific adjustable compression garment (ACG) system (Coolflex Standard Calf and Coolflex Standard Foot; Sigvaris Inc.) promotes self-care in patients with chronic leg oedema. Secondary aims were to assess the effectiveness of this ACG in reducing oedema, improving patient reported outcomes, and determining the patients' degree of satisfaction with the handling of the wrap. METHODS: This was a multicentre prospective observational study. The study included 99 adult patients aged 18 - 90 years presenting with chronic oedema of the lower extremity, which encompasses conditions such as lymphoedema, venous oedema, and phlebolymphoedema. At baseline, all patients received an ACG. After two to three days and after six weeks, their overall satisfaction with the therapy was assessed. Leg volume was determined in a contactless manner during the baseline and follow up visits. All patients completed the cross cultural adaptation of the Lymphoedema Functioning, Disability and Health Questionnaire for Patients with Lymphoedema of the Lower Extremity in Germany (Lymph-ICF-UG). RESULTS: A total of 86 patients completed the study and were followed up for six weeks. At the final six week follow up, 82 (95.3%) of the 86 subjects indicated that they were able to put on the wrap independently or with a little help from relatives. The overall satisfaction rate was 88.0% (95% confidence interval [CI], 79.64 - 93.9%). The mean leg volume reduction from baseline to six weeks was -4.7% (95% CI -6.3 - -3.0%; p < .001). Lymph-ICF-UG scores and scores in all domains improved significantly from baseline to the final follow up. CONCLUSION: The ACG used in this study was found to promote self-care in a high proportion of patients with chronic leg oedema. A significant reduction in oedema was observed.

One versus two vein anastomoses in breast reconstruction with a profunda artery perforator flap-does it make a difference.

BACKGROUND: The profunda artery perforator (PAP) flap has gained popularity as a reliable alternative in breast reconstruction. Extensive research has focused on its vascular supply, dissection techniques, and broader applications beyond breast reconstruction. This study aims to investigate the correlation between the number of veins anastomosed for the PAP flap and postoperative complications. METHODS: A retrospective study was conducted to evaluate the outcomes of breast reconstructions with PAP flaps at our institution between 2018 and 2022. A total of 103 PAP flaps in 88 patients were included. Statistical analysis was performed to compare outcomes between flaps with one vein anastomosis and those with two vein anastomoses. Patient characteristics, intra and postoperative parameters were analysed. RESULTS: One vein anastomosis was used in 36 flaps (35.0%), whereas two vein anastomoses were used in 67 flaps (65.0%). No significant differences were found in patient characteristics between the one vein and two vein groups. The comparison of ischemia times between flaps with one versus two veins revealed no statistically significant difference, with mean ischemia times of 56.2 ± 36.8 min and 58.7 ± 33.0 min, respectively. Regarding outcomes, there were no statistically significant differences in secondary lipofilling, revision of vein anastomosis, or total flap loss between the two groups. Fat necrosis was observed in 5 (13.9%) one vein flaps and 5 (7.5%) two vein flaps, indicating no statistically significant difference between the two groups (p = .313). In the one vein group, the most frequently employed coupler ring had a diameter of 2.5 mm. In the two vein group, the most prevalent combination consisted of a 2.0 mm diameter with a 2.5 mm diameter. CONCLUSION: Based on our study results, both one vein anastomosis and two vein anastomoses are viable options for breast reconstruction with PAP flap. The utilization of either one or two veins did not significantly affect ischemia time or flap loss. Fat necrosis exhibited a higher incidence in the single-vein group; however, this difference was also not statistically significant. These findings underscore the effectiveness of both approaches, providing surgeons with flexibility in tailoring their surgical techniques based on patient-specific considerations and anatomical factors.

An innovative flat-knit compression garment for lymphoedema patients led to better outcomes: a multicentre study.

OBJECTIVE: To evaluate the clinical performance, quality of life (QoL) and patient satisfaction with an innovative flat-knit compression garment for the daytime treatment of lymphoedema patients in daily routine. METHOD: In a prospective multicentre observational study, patients with leg or arm lymphoedema (stage I-II, International Society of Lymphology (ISL) standards, 2016) received a made-to-measure flat-knit compression class 2 JOBST Confidence (BSN-JOBST GmbH, Germany) thigh-high stocking or arm sleeve. Primary endpoint was the oedema status as determined by the mean sum of the circumferences at the beginning and the end of the wearing period. Secondary endpoints included QoL-related parameters and patient satisfaction with product features assessed through questionnaires. The observation period lasted three weeks. RESULTS: A total of 97 patients (87 females, 10 males), of which 65 had leg lymphoedema and 32 had arm lymphoedema, received the study device. The oedema status was effectively maintained (slight reduction in mean sum of circumferences by -3.1±7.3cm; p=0.0001). For QoL-related parameters, the patients reported fewer limitations in work, leisure and psychological wellbeing after wearing the stocking or arm sleeve (all p-values <0.0001). They also experienced less limitations in function and movement, feeling of tension and heaviness, and fewer difficulties wearing clothes, shoes, jewellery or watches at study end (all p-values <0.0001). In terms of pleasant feeling on the skin, moisture management, softness of material, range of motion, overall wearing comfort and heat build-up under the garment, patients were more satisfied with the tested compression garment than with previously worn compression garments (all p-values <0.001). CONCLUSION: In this study, the tested innovative compression product increased patient satisfaction with the improved product features while the lymphoedema status was successfully maintained.

Venous disorders as an occupational disease - a systematic review on epidemiology, pathophysiology, and modification strategies.

Forced postures are common in the workplace. Work in the primary economic sector is characterised by a high degree of physical activity and movement; however, activities in the secondary and tertiary sectors commonly require workers to stand or sit. An expansion of the tertiary sector in recent decades has meant that people in industrialised and emerging economies primarily sit or stand at work. The aim of the systematic review was to identify occupational factors relating to the presence of chronic venous disease (CVD), to place these in the context of developments in the workplace, and to determine whether measures are in place to prevent CVD. We performed a systematic literature review to analyse studies assessing work-related risk factors for CVD. We searched for publications in the PubMed database, the clinic library of BG Hospital Bergmannstrost Halle, and the registry of the German Statutory Accident Insurance. Using occupation-specific keyword combinations, we identified 27,522 publications. The publications underwent an automatic and manual filtering process according to the PRISMA guidelines and 81 publications qualified for the review. Ultimately 25 studies were included in the systematic review. All of the subjects of the studies worked in the secondary and tertiary sectors. No studies looked at the relationship between venous disorders and primary sector occupations. Standing at work for more than four hours a day, repeated heavy lifting, and cumulative time working in a sitting or standing position are risk factors for the development of CVD. Sitting is less of a risk factor than standing or walking. Occupational history and the patient's activity profile are important diagnostic tools which can help confirm a diagnosis and justify treatment when findings are inconsistent. Compression therapy is the primary form of secondary and tertiary prevention. There continues to be a lack of primary preventive measures related to workplace design.

Tolerance Induction in Vascularized Composite Allotransplantation-A Brief Review of Preclinical Models.

Pre-clinical studies are an obligatory tool to develop and translate novel therapeutic strategies into clinical practice. Acute and chronic rejection mediated by the recipient's immune system remains an important limiting factor for the (long-term) survival of vascularized composite allografts (VCA). Furthermore, high intensity immunosuppressive (IS) protocols are needed to mitigate the immediate and long-term effects of rejection. These IS regiments can have significant side-effects such as predisposing transplant recipients to infections, organ dysfunction and malignancies. To overcome these problems, tolerance induction has been proposed as one strategy to reduce the intensity of IS protocols and to thereby mitigate long-term effects of allograft rejection. In this review article, we provide an overview about animal models and strategies that have been used to induce tolerance. The induction of donor-specific tolerance was achieved in preclinical animal models and clinical translation may help improve short and long-term outcomes in VCAs in the future.

Regeneration of the entire human epidermis using transgenic stem cells.

Junctional epidermolysis bullosa (JEB) is a severe and often lethal genetic disease caused by mutations in genes encoding the basement membrane component laminin-332. Surviving patients with JEB develop chronic wounds to the skin and mucosa, which impair their quality of life and lead to skin cancer. Here we show that autologous transgenic keratinocyte cultures regenerated an entire, fully functional epidermis on a seven-year-old child suffering from a devastating, life-threatening form of JEB. The proviral integration pattern was maintained in vivo and epidermal renewal did not cause any clonal selection. Clonal tracing showed that the human epidermis is sustained not by equipotent progenitors, but by a limited number of long-lived stem cells, detected as holoclones, that can extensively self-renew in vitro and in vivo and produce progenitors that replenish terminally differentiated keratinocytes. This study provides a blueprint that can be applied to other stem cell-mediated combined ex vivo cell and gene therapies.

Transgenic skin biomechanical properties following first lifesaving epidermal regeneration using combined gene and cell therapy.

BACKGROUND: In 2017, we reported the first life-saving regeneration of virtually an entire epidermis by combined gene and stem cell therapy. Recently, we demonstrated excellent long-term stability of this transgenic epidermis. Skin quality in this experimental approach and its potential application in other conditions were elucidated here regarding long-term outcomes of biomechanical properties. PATIENTS AND METHODS: Analysis of biomechanical properties including skin elasticity, anisotropy and friction was performed on multiple body sites 24, 36 and 60 months following transplantation. Firstly, the sites were matched against and compared to remaining stable non-transgenic areas as well as to a control group of 13 healthy subjects. Parameters for skin elasticity, deformation and friction were assessed non-invasively. RESULTS: Biomechanical properties of the transgenic epidermis showed encouraging results in comparison to both the remaining stable non-transgenic skin as well as healthy controls. Skin elasticity was comparable to the controls. Skin friction showed some decrease in both transgenic and non-transgenic areas as compared to the controls. CONCLUSIONS: The excellent functional outcomes of the transgenic epidermis demonstrate stable long-term results of this novel combined gene and stem cell therapy for epidermal regeneration. Thus, other applications for this technology, such as treatment of specific burns, should be explored.

Breaking the circle-effectiveness of liposuction in lipedema.

BACKGROUND: Lipedema is a common chronic fat distribution disorder often aligned with pain and reduced quality of life affecting 6-10% of the female population. Although lipedema has acquired more scientific attention in the last decade, validated diagnosis and treatment still remain challenging for specialists. PATIENTS AND METHODS: In this article we evaluate the effect of liposuction on appearance, pain and coexisting diseases of 860 patients with lipedema. Comparison among stages of lipedema pre- and post-liposuction was performed by using t-Tests for independent samples and Kruskal-Wallis-Tests. RESULTS: Our study demonstrates the positive effect on pain reduction in patients with lipedema after liposuction (NRS 2.24) compared with pre-liposuction pain perception (NRS 6.99) and pain perception of patients with conservative treatment (NRS 6.26). Significant differences were shown in the perception between the stages of lipedema and in the reduction of pain perception by liposuction. Furthermore we examined co-diseases in patients with lipedema, primarily menstruation complaints (43%), sleeplessness (36%) and migraine (35%). CONCLUSIONS: A progress of lipedema disease leads not only to a change of appearance and proportion but also to a progressive increase of pain. Liposuction shows a significant effect on pain reduction -independent of the patients' stage of lipedema.

A systematic review of cardiovascular risk factors in patients with traumatic spinal cord injury.

Objective: The main risk factors for cardiac events, and particularly for the development of atherosclerosis, are diabetes mellitus, arterial hypertension, dyslipidemia and smoking. Patients with a traumatic spinal cord injury (SCI) may present with autonomic nervous system dysfunction depending on their level of spinal cord injury. Studies have found a rise in cardiovascular mortality. A systematic review was conducted that focused on this patient group's predisposition to vascular risk. Methods: We performed a PubMed and Cochrane database search. After applying specific search criteria, 42 articles were included in our analysis out of a total of 10,784 matches. The articles were selected with the aim of establishing cardiovascular risk factors in patients with traumatic spinal cord injury. Results: Patients with SCI are at an increased risk for peripheral artery disease even in the absence of cardiovascular risk factors. Major vascular changes to the arteries of patients with SCI include: a reduction in lumen size, increased vessel wall tension, higher vascular stiffness, an impaired reactive hyperemic response, and a lack of reduced vascular resistance. The findings for carotid atherosclerosis were inconclusive. This group of patients also has a higher disposition for diabetes mellitus, lipid metabolism disorders and coronary artery disease. Paraplegics are more likely to suffer from dyslipidemia, obesity and PAD, while tetraplegics are more likely to have diabetes mellitus. Conclusions: Patients with SCI are more likely to have cardiovascular risk factors and have cardiovascular disease compared to the normal population. Peripheral circulatory disorders are particularly common. Patients with SCI are now considered to be a new risk group for cardiovascular disease; however, large epidemiological studies are needed to verify in more detail the cardiovascular risk profile of this patient group.

Breast Reconstruction- Developing a Volumetric Outcome Algorithm.

Postoperative loss of breast volume represents a significant parameter for outcome evaluation of breast reconstruction. Breast volume broadly varies- depending of reconstruction method as well as surgical differences. A structural pattern of breast volume loss provides an essential parameter for preoperative design, helps to reduce postoperative breast asymmetry rate and thereby the need for reoperation. Therefore we hereby compare volume change of the three main reconstruction techniques: autologous flap-based, prosthesis-based and autologous fat transplantation breast reconstruction. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Volumetry in Breast Reconstruction: Always New, Always Better?

Although breast surgeries for aesthetic or reconstructive purposes are regularly performed, no focus has been laid on establishing an adequate and reliable volumetry method. While CT and MRI scan represent methods that are already in clinical use, the 3D scan  is a novel and promising tool, easy to use with the possibility to measure the anatomic breast volume in an upright position. Nevertheless, its reliability is broadly underinvestigated. LEVEL OF EVIDENCE V : This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Understanding Breast Implant Illness: Etiology is the Key.

Because breast augmentation is one of the most popular cosmetic procedures, the issue of implant-related complications has been widely debated ever since the FDA approved the use of implants in 1962. Although decades have passed, breast implant illness (BII) still represents a poorly defined and controversial complication. With ongoing nonscientific discussion in the mainstream media and on social media, revealing the etiology of BII is urgent because knowledge of this subject ultimately influences patients' decisions. Little or no scientific research is currently available on BII and no final conclusions regarding its etiology, clinical manifestations, diagnostic criteria, or treatment have been made. This review aims to give an overview of the hypotheses on the etiology of BII and seeks inspiration to improve the conditions of BII patients.

Vascular trauma of the hand - a systematic review.

Hypothenar or thenar hammer syndrome (HHS) and hand-arm vibration syndrome (HAVS) are diseases caused by acute or chronic trauma to the upper extremities. Since both diseases are generally related to occupation and are recognised as occupational diseases in most countries, vascular physicians need to be able to distinguish between the two entities and differentiate them from other diagnoses. A total of 867 articles were identified as part of an Internet search on PubMed and in non-listed occupational journals. For the analysis we included 119 entries on HHS as well as 101 papers on HAVS. A professional history and a job analysis were key components when surveying the patient's medical history. The Doppler-Allen test, duplex sonography and optical acral pulse oscillometry were suitable for finding an objective basis for the clinical tests. In the case of HHS, digital subtraction angiography was used to confirm the diagnosis and plan treatment. Radiological tomographic techniques provided very limited information distal to the wrist. The vascular component of HAVS proved to be strongly dependent on temperature and had to be differentiated from the various other causes of secondary Raynaud's phenomenon. The disease was medicated with anticoagulants and vasoactive substances. If these were not effective, a bypass was performed in addition to various endovascular interventions, especially in the case of HHS. Despite the relatively large number of people exposed, trauma-induced circulatory disorders of the hands can be observed in a comparatively small number of cases. For the diagnosis of HHS, the morphological detection of vascular lesions through imaging is essential since the disorder can be accompanied by critical limb ischaemia, which may require bypass surgery. In the case of HAVS, vascular and sensoneurological pathologies must be objectified through provocation tests. The main therapeutic approach to HAVS is preventing exposure.

Influence of preadipocyte-conditioned medium on the proliferation and invasive potential of breast cancer cell lines in vitro.

PURPOSE: Autologous transplantation of adipose tissue into the breast is commonly performed in clinical practice, but its oncological safety has not been established. METHODS: We conducted an in vitro study to assess the influence of factors released by adipose-derived stem cells (ASCs), from multiple source tissues and harvested using different techniques, on proliferation and invasiveness of two breast cancer cell lines. RESULTS: Fat specimens of 66 donors (57 female, 9 male) were collected and 44 ASC cultures were established. ASC conditioning of the medium (CM) increased the proliferation of MCF-7 cells (178.4 ± 62.8%; P < 0.001), whereas MDA-MB321 proliferation was decreased (87.3 ± 15.3%; P = 0.032). We observed increased cell migration (174.0 ± 62.8%; P = 0.002), but not cell invasion (1.28 ± 0.51; P = 0.14) in MDA-MB231. Migration and invasion of MCF-7 cells were not affected by exposure to ASC-CM. For MCF-7 cell migration, lower BMI (< 25 kg/m2) was associated with increased migration, both in univariate (P = 0.015) and multivariate (P = 0.039) analyses. Regarding the cytokine secretome, proliferation of MCF-7 was positively correlated with levels of eotaxin 1 and insulin-like growth factor-binding protein 3 in the CM, and inversely correlated with levels of interleukin 1ß and transforming growth factor ß-3. In case of MDA-MB231, granulocyte colony-stimulating factor, angiogenin, eotaxin 1 and 3, neutrophil activating peptide 2, and neurotrophin-3 were positively correlated with proliferation. CONCLUSIONS: We conclude that fat tissue transplantation increases proliferation and migration, but not invasion, of breast cancer cells. These findings are consistent with clinical data regarding the safety of autologous fat transplantation in breast cancer patients.

Extracorporeal Perfusion in Vascularized Composite Allotransplantation: Current Concepts and Future Prospects.

Severe injuries of the face and limbs remain a major challenge in today's reconstructive surgery. Vascularized composite allotransplantation (VCA) has emerged as a promising approach to restore these defects. Yet, there are major obstacles preventing VCA from broad clinical application. Two key restrictions are (1) the graft's limited possible ischemia time, keeping the potential donor radius extremely small, and (2) the graft's immunogenicity, making extensive lifelong monitoring and immunosuppressive treatment mandatory. Machine perfusion systems have demonstrated clinical success addressing these issues in solid organ transplantation by extending possible ischemia times and decreasing immunogenicity. Despite many recent promising preclinical trials, machine perfusion has not yet been utilized in clinical VCA. This review presents latest perfusion strategies in clinical solid organ transplantation and experimental VCA in light of the specific requirements by the vascularized composite allograft's unique tissue composition. It discusses optimal settings for temperature, oxygenation, and flow types, as well as perfusion solutions and the most promising additives. Moreover, it highlights the implications for the utility of VCA as therapeutic measure in plastic surgery, if machine perfusion can be successfully introduced in a clinical setting.

[Focus on the Hand - an Interface Between Surgery and Vascular Medicine]. / Die Hand im Fokus ­ Schnittstellen zwischen Chirurgie und Gefäßmedizin.

Damage to the hand caused by vibration has been observed with a range of trades and professions and in connection with various types of sport. Osseous, neurogenic and vascular lesions can lead to chronic ailments and permanent functional impairment. Hand-arm vibration syndrome (HAVS) and hypothenar/thenar hammer syndrome (HHS, THS) are interesting for vascular medicine. From a surgical perspective, there is a special significance in the fact that both syndromes are recognised occupational diseases (BK 2104 and BK 2114) which have to be acknowledged by an accident insurance doctor and in the medical report. Hypothenar/thenar hammer syndrome is caused by repeated force exerted in the region of the small finger or the ball of the thumb and is characterised by a trauma-induced lesion of the ulnar artery or radial artery that can lead to pain due to ischaemia in the acral area supplying blood to the arteries of the affected hand, usually the dominant hand. It is considered to be hand-arm vibration syndrome when there is a heightened sensitivity to coldness with vasospastic circulatory disturbance. The paper presents various clinical and functional diagnostic tests to enable a diagnosis. Doppler and duplex ultrasound exploration play an important role. Various radiological methods can augment diagnostic testing. The symptoms can be treated using medication or physiotherapy to improve perfusion by stimulating vasodilatation. An effective causal therapy is currently not available. Thus, when drawing up the medical report, particular attention should be paid to gathering information about the patient's medical history so that an unequivocal link can be made between the cause of the damage and the physical damage, as this could have sociomedical and pension-relevant consequences for the patient.

Varicose vein therapy and nerve lesions.

Treating varicose veins using endovenous thermal techniques - especially laser and radio frequency ablation - has emerged as an effective alternative to open surgery with stripping and high ligation. Even though these methods are very gentle and patient-friendly, they are nevertheless accompanied by risks and side effects. Compared to open surgical therapy, the risk of damage to peripheral and motor nerves is reduced; however, it still exists as a result of heat exposure and tumescent anaesthesia. Non-thermal methods that can be applied without tumescent anaesthesia have been introduced to the market. They pose a considerably lower risk of nerve lesions while proving to be much more effective. This paper investigates data on postoperative nerve damage and paraesthesia using internet research (PubMed). It analyses the current state of knowledge regarding non-thermal treatment methods and takes into account the latest developments in the use of cyanoacrylate to close insufficient saphenous veins.