Subcutaneous mastectomy in female-to-male transsexuals is associated with higher risk of postoperative bleeding complications.

Introduction: Chest contouring or subcutaneous mastectomy (SCM) in female-to-male (FtM) transgender individuals is the primary surgery in the gender reassignment process. Many authors report high rates of postoperative bleeding in these patients and discuss a possible influence of preoperative hormone therapy. However, there is a lack of data on the analysis between different surgical techniques and postoperative bleeding risk. Materials and Methods: In this retrospective study, we included 22 FtM transgender individuals who underwent bilateral SCM using 4 different techniques (44 breasts) between June 2014 and September 2023. Postoperative complications regarding surgical techniques and patient demographics were collected and analyzed. Results: SCM with free nipple grafting was the most commonly used technique (n = 12, 54.5%). The mean operative time was 163.4 ± 49.2 minutes. There were no significant differences in operative time between the surgical techniques (p ≥ 0.20 in all cases). The rate of acute postoperative bleeding was 20.5% (n = 9). Acute postoperative bleeding occurred most frequently in patients who received a semi-circular incision for SCM. There was no significant difference in the rate of acute postoperative bleeding between the different surgical techniques. BMI, breast weight, and duration of surgery were not associated with the rate of acute complications (p > 0.17 in all cases). Conclusions: Less invasive SCM techniques in FtM transgender individuals are associated with higher postoperative bleeding risk.

Blood Vessel Injuries of the Fingers: A Clinical Comparison of One- and Two-Arterial Blood Supply.

Traumatic finger injuries are very common in emergency medicine. When patients present with finger injuries, there is often damage to the vascular nerve bundles, which requires subsequent reconstruction. It is unknown if repairing a unilaterally injured artery affects patients' recovery in a well-perfused finger. This retrospective cohort study compares the clinical outcomes of 11 patients with one-vessel supply (mean age 48.3 years; 7 males, 4 females) to 14 patients with two-vessel supply (mean age 44.5 years; 8 males, 6 females). The patient outcomes were assessed using patient questionnaires (Disabilities of Arm, Shoulder, and Hand (DASH), European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L), and EuroQol visual analog scale (EQ-VAS)) and a clinical examination of hand function and imaging of circulatory efficiency. No significant changes were observed in the DASH, EQ-5D-5L, and EQ-VAS questionnaires. Clinical evaluation of hand function, measured by cold sensitivity, two-point discrimination, pain numerical analog scale, and grip strength also revealed no significant differences between cohorts. Blood flow measurements using thermal imaging revealed no effects on circulation in the affected digit. Collectively, the study finds reconstruction is not absolutely necessary when there is one intact digital artery as it is sufficient for healing and functional outcomes. We recommend finger artery reconstruction when both digital arteries are injured or if an immediate tension-free suture is possible.

A new fasciocutaneous flap model identifies a critical role for endothelial Notch signaling in wound healing and flap survival.

Flap surgery is a common treatment for severe wounds and a major determinant of surgical outcome. Flap survival and healing depends on adaptation of the local flap vasculature. Using a novel and defined model of fasciocutaneous flap surgery, we demonstrate that the Notch ligand Delta-like 1 (Dll1), expressed in vascular endothelial cells, regulates flap arteriogenesis, inflammation and flap survival. Utilizing the stereotyped anatomy of dorsal skin arteries, ligation of the major vascular pedicle induced strong collateral vessel development by end-to-end anastomosis in wildtype mice, which supported flap perfusion recovery over time. In mice with heterozygous deletion of Dll1, collateral vessel formation was strongly impaired, resulting in aberrant vascularization and subsequent necrosis of the tissue. Furthermore, Dll1 deficient mice showed severe inflammation in the flap dominated by monocytes and macrophages. This process is controlled by endothelial Dll1 in vivo, since the results were recapitulated in mice with endothelial-specific deletion of Dll1. Thus, our model provides a platform to study vascular adaptation to flap surgery and molecular and cellular regulators influencing flap healing and survival.

Factor XIII: More than just a fibrin stabilizer for the burn patient? A matched-pair analysis.

Background: Acquired factor XIII deficiency is an underestimated risk in patients with large surface burns, which potentially exposes these patients to prolonged bleeding and delayed wound healing if undetected. Methods: A retrospective matched-pair analysis of the burn registry of the Department of Plastic, Aesthetic, Hand, and Reconstructive Surgery of Hannover Medical School was performed from 2018 to 2023. Results: A total of 18 patients were included. Acquired factor XIII deficiency was not statistically significant correlated with age, sex, or body mass index. Patients who developed acquired factor XIII deficiency had a significantly longer hospital stay (72.8 days) compared with those in the matched group (46.4 days), although burn depths, total body surface area, and Abbreviated Burn Severity Index were not statistically correlated with factor XIII deficiency. Conclusions: Little is known about acquired factor XIII deficiency in patients with burns. Factor XIII supplementation may improve hemostasis, wound healing, and general outcome while reducing the patient's exposure to blood products.

The modified 5-item frailty index as a predictor of complications in burn patients.

The modified 5-item frailty index (mFI-5), as a measure of frailty and biological age, has been shown to be a reliable predictor of complications and mortality in a variety of surgical specialties. However, its role in burn care remains to be fully elucidated. We, therefore, correlated frailty with in-hospital mortality and complications after burn injury. The medical charts of all burn patients admitted between 2007 and 2020 who had ≥ 10 % of their total body surface area affected were retrospectively reviewed. Data on clinical, demographic, and outcome parameters were collected and evaluated, and mFI-5 was calculated on the basis of the data obtained. Univariate and multivariate regression analyses were used to investigate the association between mFI-5 and medical complications and in-hospital mortality. A total of 617 burn patients were included in this study. Increasing mFI-5 scores were significantly associated with increased in-hospital mortality (p < 0.0001), myocardial infarction (p = 0.03), sepsis (p = 0.005), urinary tract infections (p = 0.006), and perioperative blood transfusions (p = 0.0004). They were also associated with an increase in the length of hospital stay and the number of surgical procedures, albeit without statistical significance. An mFI-5 score of ≥ 2 was a significant predictor of sepsis (odds ratio [OR] = 2.08; 95% confidence interval [CI]: 1.03 to 3.95; p = 0.04), urinary tract infection (OR = 2.82; 95% CI: 1.47 to 5.19; p = 0.002), and perioperative blood transfusions (OR = 2.61; 95% CI: 1.61 to 4.25; p = 0.0001). Multivariate logistic regression analysis revealed that an mFI-5 score of ≥ 2 was not an independent risk factor for in-hospital mortality (OR = 1.44; 95% CI: 0.61 to 3.37; p = 0.40). mFI-5 is a significant risk factor for only a few select complications in the burn population. It is not a reliable predictor of in-hospital mortality. Therefore, its utility as a risk stratification tool in the burn unit may be limited.

Personalized Treatment Decisions for Traumatic Proximal Finger Amputations: A Retrospective Cohort Study.

Ray and proximal phalanx amputations present valid surgical options for the management of severe traumatic finger injuries. However, among these procedures, the superior one for optimal functionality and quality of life for patients still remains unknown. This retrospective cohort study compares the postoperative effects of each amputation type to provide objective evidence and to create a paradigm for clinical decision-making. A total of forty patients who had received either ray or proximal phalanx-level amputations reported on their functional outcomes using a combination of questionnaires and clinical testing. We found a decreased overall DASH score following ray amputation. Particularly, Part A and Part C of the DASH questionnaire were consistently lower compared with amputation at the proximal phalanx. Pain measurements in the affected hand were also significantly decreased during work and at rest in ray amputation patients, and they reported decreased cold sensitivity. Range of motion and grip strength were lower in ray amputations, which is an important preoperative consideration. We found no significant differences in reported health condition, evaluated according to the EQ-5D-5L, and blood circulation in the affected hand. We present an algorithm for clinical decision-making based on patients' preferences to personalize treatment.

Cell Dissociation Techniques in Salamanders.

Cell dissociation is an important technique for the study of tissue phenotypes. The method chosen to harvest cells from solid tissues profoundly influences the types of cells recovered. Methodology also shapes any biases that are introduced that can act upon cell surface protein phenotypes or gene expression. Here we describe examples of cell surface phenotypic changes and typical yields, under 4 different isolation conditions (enzymatic/non-enzymatic), using the axolotl spleen, and the regenerating limb. We describe simple methods for evaluating the liberation of viable cells and the downstream characterization of cell diversity using a live-cell flow cytometry approach. Of note, the cellular composition of dissociated cells and surface antigen detection vary with each condition. TrypLE and "no enzyme" protocols give the highest surface marker expression, but poor liberation of non-immune cells in the blastema. Liberase-DH and Liberase-TL have alternative neutral proteases and both give acceptable dissociation of diverse cell types in the blastema. Liberase-TL provides the highest yield of all cell sizes and a larger non-immune fraction. Matching dissociation times between limb blastemas and spleens, we demonstrate the effect of "over-digestion" in soft tissues. In the spleen, the Liberase enzyme cocktails produced the lowest yields, worst viability, and the greatest loss of immune cell surface markers, when compared with non-enzymatic and TrypLE dissociation. These examples provide a template for optimizing protocols for individual tissues while achieving the balance between cell recovery and the mitigation of cellular changes appropriate for downstream applications such as single-cell RNA sequencing and flow cytometry.

Attempted Suicide by Burning: A Cross-sectional Analysis at a Regional Burn Center in Germany.

Attempted suicide by self-immolation or burning constitutes an uncommon form of attempted suicide in high income countries, presenting substantial challenges to burn units. The aim of this study was to analyze the epidemiologic characteristics and outcomes in intensive care burn patients treated for attempted suicide by burning. For this purpose, we examined intensive care burn patients admitted to a single major burn unit between March 2007 and December 2020. Demographic, clinical, epidemiological, and mortality data were collected and analyzed. Major psychiatric comorbidities were evaluated according to ICD-9 and ICD-10 classifications. A total of 1325 intensive care unit burn patients were included. Suicide by burning was attempted in 45 cases (3.4%). Attempted suicide victims presented with significantly higher burn severity, reflected by higher abbreviated burn severity index scores, and larger TBSA affected. Burned TBSA ≥30% and inhalation injuries were observed more frequently in suicidal patients. These patients also experienced prolonged hospital and intensive care unit length of stay, required surgical interventions and mechanical ventilation more frequently, and had significantly longer periods on ventilation, causing an overall higher mortality rate (24.4%). Psychiatric comorbidities were present in 75.6% of patients who attempted suicide. Despite the low prevalence, burn severity and mortality are considerably high in patients who attempted suicide by burning, presenting a significant challenge for healthcare providers. The majority of patients had a history of psychiatric disorder, highlighting the importance of identifying patients at high-risk who may profit from increased psychiatric intervention.

In Vitro Differentiation of Myoblast Cell Lines on Spider Silk Scaffolds in a Rotating Bioreactor for Vascular Tissue Engineering.

Functional construction of tissue-engineered vessels as an alternative to autologous vascular grafts has been shown to be feasible, however the proliferation of seeded smooth-muscle cells remains a limiting factor. We employed a rotating bioreactor system to improve myoblast cell differentiation on a spider silk scaffold for tissue-engineered vessel construction. C2C12 myofibroblast cells were seeded on the surface of spider silk scaffold constructs and cultivated in a rotating bioreactor system with a continuous rotation speed (1 rpm). Cell function, cell growth and morphological structure and expression of biomarkers were analyzed using scanning electron microscopy, the LIVE/DEAD® assay, Western blot and quantitative real-time PCR analyses. A dense myofibroblast cell sheet could be developed which resembled native blood vessel muscular tissue in morphological structure and in function. Bioreactor perfusion positively affected cell morphology, and increased cell viability and cell differentiation. The expression of desmin, MYF5 and MEF2D surged as an indication of myoblast differentiation. Cell-seeded scaffolds showed a tear-down at 18 N when strained at a set speed (20 mm min-1). Spider silk scaffolds appear to offer a reliable basis for engineered vascular constructs and rotating bioreactor cultivation may be considered an effective alternative to complex bioreactor setups to improve cell viability and biology.

Comparative Analysis of Composite Mortality Prediction Scores in Intensive Care Burn Patients.

Multiple outcome scoring models have been used in predicting mortality in burn patients. In this study, we compared the accuracy of five established models in predicting outcomes in burn patients admitted to the intensive care unit and assessed risk factors associated with mortality. Intensive care burn patients admitted between March 2007 and December 2020 with total body surface area (TBSA) affected ≥ 10% were analyzed. Multivariate analysis was conducted to examine variables associated with mortality. The ABSI, Ryan, BOBI, revised Baux and BUMP scores were analyzed by receiver operating characteristics. A total of 617 patients were included. Morality was 14.4%, with non-survivors being significantly older, male, and having experienced domestic burns. Multivariate analysis identified age, TBSA, full-thickness burns and renal insufficiency as independent mortality predictors. The BUMP score presented the highest mortality prognostication rate, followed by ABSI, revised Baux, BOBI and Ryan scores. BUMP, ABSI and revised Baux scores displayed AUC values exceeding 90%, indicating excellent prognostic capabilities. The BUMP score showed the highest accuracy of predicting mortality in intensive care burn patients and outperformed the most commonly used ABSI score in our cohort. The older models displayed adequate predictive performance and accuracy compared with the newest model.

A New Standardized Clinical Model for Evaluation of Nerve Guides: A Single-Blinded Randomized Controlled Prospective Study.

BACKGROUND: Autologous nerve transplantation is the accepted clinical standard for reconstruction of peripheral nerve defects. Bioengineered nerve guides as an alternative to autologous nerve transplantation have been described in previous studies and several different types are commercially available. Examination of the implementation of these devices in the clinical setting is an important step in determining their applicability in reconstructive nerve surgery. METHODS: In a single-blinded randomized controlled prospective study, the authors examined 34 patients undergoing diagnostic nerve biopsy (2 cm). The biopsy-induced nerve gap was interposed using a segment of the lesser saphenous vein in 16 patients. Eighteen patients had no nerve reconstruction and served as a control group. A further 10 participants were included as a healthy cohort. Nerve regeneration was assessed using von Frey filaments preoperatively and 1 day and 3, 6, 9, and 12 months postoperatively. RESULTS: Patients who received defect bridging of the sural nerve with a venous graft showed better regeneration of lateral foot sensitivity than patients without venous graft. CONCLUSIONS: The distal sural nerve biopsy can be used as a baseline model to evaluate peripheral nerve regeneration. Newly developed nerve guides could be tested in other unpredictable and challenging clinical peripheral nerve lesions. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Tissue origin of cytotoxic natural killer cells dictates their differential roles in mouse digit tip regeneration and progenitor cell survival.

Regeneration of amputated digit tips relies on mesenchymal progenitor cells and their differentiation into replacement bone and tissue stroma. Natural killer (NK) cells have well-characterized roles in antigen-independent killing of virally infected, pre-tumorous, or stressed cells; however, the potential for cytotoxic activity against regenerative progenitor cells is unclear. We identified NK cell recruitment to the regenerating digit tip, and NK cytotoxicity was observed against osteoclast and osteoblast progenitors. Adoptive cell transplants of spleen NK (SpNK) or thymus NK (ThNK) donor cells into immunodeficient mice demonstrated ThNK cell-induced apoptosis with a reduction in osteoclasts, osteoblasts, and proliferative cells, resulting in inhibition of regeneration. Adoptive transfer of NK cells deficient in NK cell activation genes identified that promotion of regeneration by SpNK cells requires Ncr1, whereas inhibition by ThNK cells is mediated via Klrk1 and perforin. Successful future therapies aimed at enhancing regeneration will require a deeper understanding of progenitor cell protection from NK cell cytotoxicity.

Murine embryonic fibroblast cell lines differentiate into three mesenchymal lineages to different extents: new models to investigate differentiation processes.

Various diseases, injuries, and congenital abnormalities may result in degeneration and loss of organs and tissues. Recently, tissue engineering has offered new treatment options for these common, severe, and costly problems in human health care. Its application is often based on the usage of differentiated stem cells. However, despite intensive research and growing knowledge, many questions remain unresolved in the process of cell differentiation. The aim of this study was to find standardized cell models for analyzing molecular mechanisms of cell differentiation. We investigated the multipotency of three standardized murine embryonic fibroblast cell cultures using histological staining, western blotting, and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Our results demonstrated that NIH-3T3 and mouse embryonic fibroblast (MEF) cells were able to differentiate into adipogenic, chondrogenic, and osteogenic lineages expressing typical differentiation markers. Interestingly, Flp-In-3T3 cells did not differentiate into any of the three mesenchymal lineages, although this cell line is genetically closely related to NIH-3T3. The results were confirmed by histological staining. Flp-In-3T3, NIH-3T3, and MEF cells have usually been used for DNA transfections, recombinant protein expression, and as "feeder cells." Unlike mesenchymal stem cells (MSCs) and mesenchymal progenitor cells (MPCs), they are easy to obtain and to expand and are less prone to change their structure and morphology, even at higher passages. Our results suggest that Flp-In-3T3, MEF, and NIH-3T3 cells are highly suitable to be used as models to analyze molecular mechanisms of cell differentiation.

Role of lifeguard ß-isoform in the development of breast cancer.

In the last century there has been great progress in the treatment of breast cancer by improving drug and radiation therapy as well as surgical techniques. Despite this development, breast cancer remains a major cause of death among women in Europe and the US. The cause of breast cancer at the cellular level is still not fully understood. In the present study, we investigated the expression of the Lifeguard ß-isoform in breast cancer tissues. In contrast to Lifeguard, the ß­isoform has one transmembrane domain less, which is the last of seven (99 bp), and due to this we suspect that the Lifeguard ß-isoform exhibits a different function. We determined the expression and function of the ß-isoform of Lifeguard in breast cancer cell lines (MCF-7 and MDA-MB-231), a human breast epithelial cell line (MCF10A) and in breast tumour tissue sections. Western blotting, PCR arrays and immunofluorescence were used to investigate the expression of Lifeguard and its ß-isoform. Moreover, we investigated the ability of Lifeguard ß-isoform expression to inhibit apoptosis induced by Fas. Our results indicated that Lifeguard ß-isoform is strongly expressed in breast tumour tissues. More notably, we demonstrated that Fas sensitivity was reduced in the MCF10A breast cells expressing the Lifeguard ß-isoform. Taken together, our findings indicate the role of the Lifeguard ß-isoform as an anti­apoptotic protein and provide further evidence of the potential of the Lifeguard ß-isoform as a target for the development of novel therapeutic strategies.