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

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

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

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

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

SUMMARY: 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

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

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

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

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

Summary: 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