Background  Foot ulcer is a common complication of poorly controlled diabetes and peripheral vascular disease (PVD). The current standard of treatment for diabetic foot ulcers includes the management of underlying risk factors, wound debridement, use of antibiotics for infection, off-loading with cast, and revascularisation surgery. The glyceryl trinitrate (GTN) patch is currently off-licence in treating PVD or diabetic foot ulcers. This study aims to evaluate the effectiveness of the GTN patch in preventing amputation, improving pain control, and reducing the size of tissue loss (ulcer/gangrene) or localised ischaemic area. Method This is a pilot study of 30 patients who were started on the GTN patch from February 2020 to October 2021. Inclusion criteria were patients who have critical limb-threatening ischaemia (CLTI) and with no viable options or are at high risk for revascularisation, both endovascular and open surgery. Patients who were on a GTN patch for less than six weeks at the time of data collection or had unclear outcomes were excluded. The outcomes were retrospectively collected on prevention of amputation, improvement in pain control, and reduction in tissue loss (the size of ulcer/gangrene) or localised ischaemic area with the use of a GTN patch. The binomial test was used to compare the observed outcome of the GTN patch and the expected outcome, which was assumed to be 50% in this study. Results  Ninety-three per cent (93%) of the patients who had GTN patches successfully avoided amputation (p<0.0001). Eighty-four per cent (84%) of patients reported better pain control (p=0.0022) and improvement in the size of ulcer/gangrene/localised ischaemic areas (p=0.0005). Conclusion The GTN patch is effective in preventing amputation, improving pain control, and reducing the size of ulcer/gangrene/localised ischaemic areas in patients who have end-stage CLTI and no viable options or who are at high risk for revascularisation surgery.

UNASSIGNED: To introduce a new surgical method for the repair of a large inner canthus combined with tissue loss at the inner canthal angle of the eye by using a bird-beak-type z-shaped asymmetrical flap and to summarize its clinical effect.
UNASSIGNED: A total of 56 patients with a large inner canthus were randomly selected, and a bird-beak-type z-shaped asymmetrical flap was used on the nasal side of the lower eyelid to repair and reconstruct the inner canthal folds. The inner canthal point was located according to physiological aesthetics. The short and long arms of the z-shaped asymmetrical flap were separated, replaced, fixed, and shaped to reconstruct the skin folds of the inner canthus and restore its aesthetic morphology.
UNASSIGNED: All incisions after surgery achieved primary healing, and all 56 cases were followed up for 6-20 months (average 8.6 months). The caruncula lacrimalis was moderately exposed, the inner canthal angles possessed a natural appearance, and the results of the surgery were satisfactory. Five patients developed scar hyperplasia within one month after surgery, and arnica gel was applied topically for 3-6 months until the scar faded or disappeared, but no obvious scars were seen in the surgical area of the remaining patients. In two patients, the internal canthi were asymmetrical, but this improved after adjustment.
UNASSIGNED: Repair of a large inner canthus and tissue loss at the inner canthal angle of the eye using a bird-beak-type z-shaped asymmetrical flap is a simple operation, resulting in minimal trauma. Postoperatively, the inner canthal angle possessed a natural appearance with no obvious scarring.

BACKGROUND: Treatment of fingers tissue loss is particularly challenging as it often necessitates advanced reconstructive techniques such as flaps or grafts, with esthetic and functional results that are not always as good as hoped for, with long healing times. Recently, along with tissue engineering development, numerous types of dermal substitute have been commercialized, with promising possibilities of treatment in finger tissue loss. In the author\'s unit, Matriderm® is the most commonly used dermal substitute. As described by the manufacturer, this scaffold is designed to be covered with a split-thickness skin graft. In using a two-step procedure, the authors realized that in most cases of fingertips injuries, at three weeks follow-up, the wound appeared in an advanced state of healing, which permitted to avoid grafting.
METHODS: Between October 2017 and October 2018, 27 fingers have been included in this study. Patients have been divided in two groups: those treated with Matriderm® alone (15 fingers) and those who had a skin graft three weeks after the first surgery (12 fingers). At the 6-month follow-up, authors evaluated the esthetic results with the Vancouver Scar Scale (VSS), the functional results with Quick Disability of the Arm, Shoulder and Hand (qDASH) score, and sensibility by the mean of two-point discrimination test (2-PD).
RESULTS: All outcomes were overlapping in patients treated with or without skin graft: mean VSS was 2.3, mean qDASH was 13.3, and mean 2-PD was 7.7 mm.
CONCLUSIONS: The results obtained allow to consider Matriderm® , used also without skin graft coverage, as a valid solution for treatment of fingertip tissue loss.

OBJECTIVE: The aim of this study was to determine the relationship between preoperative nutritional status and wound healing in patients undergoing surgical reconstruction for ischemic tissue loss.
METHODS: The preoperative nutritional status of patients who underwent surgical reconstruction for ischemic tissue loss for the years 2011-2018 was retrospectively estimated using the Controlling Nutritional Status (CONUT) score. Patients were allocated to two groups: Group I, normal nutrition or mild malnutrition (CONUT score ≤4), and Group II, moderate-to-severe malnutrition (CONUT score ≥5). Wound healing was set as the primary endpoint and major amputation and death as the secondary endpoints. The wound healing, limb salvage, and overall survival rates were calculated after two years using the Kaplan-Meier method, and Cox proportional hazards regression analysis was performed to determine which variables were independently associated with these outcomes.
RESULTS: Forty-eight patients with missing values for the CONUT score were excluded. A total of 174 limbs in 147 patients were studied (Group I: 115 limbs in 100 patients; Group II: 59 limbs in 47 patients). The mean duration of the study was 519 ± 270 days. The Kaplan-Meier curves showed that wound healing in Group I was superior to that in Group II (Group I vs. II: two-year wound healing, 97% vs. 79%; time to 50% wound healing, 83 vs. 150 days, p < 0.001), and multivariate analysis showed that the CONUT score was an independent predictor of wound healing (hazard ratio, 0.63; 95% confidence interval, 0.41-0.98; p = 0.038).
CONCLUSIONS: Patients with better preoperative nutritional status are more likely to experience wound healing earlier than those with excessive malnutrition.

OBJECTIVE: Widespread adoption of endovascular therapy for the treatment of chronic limb-threatening ischemia has transformed the field of vascular surgery. In this modern era, we aimed to define where open surgical interventions are of greatest benefit for limb salvage.
METHODS: Patients who underwent interventions for chronic limb-threatening ischemia were identified in the vascular-targeted lower extremity National Surgical Quality Improvement Program database for open surgical interventions (OPEN) and endovascular surgical interventions (ENDO) from 2011 to 2017. Patients were further stratified based on the criteria of chronic limb-threatening ischemia (rest pain or tissue loss), and the location of the diseased arteries (femoropopliteal or tibioperoneal). The main outcomes measured included 30-day mortality, amputation, and major adverse cardiovascular events.
RESULTS: A total of 17,193 patients were revascularized for chronic limb-threatening ischemia: 10,532 were OPEN and 6661 were ENDO. OPEN had higher 30-day mortality, major adverse cardiovascular events, pulmonary, renal dysfunction, and wound complications. However, OPEN resulted in significantly lower 30-day major amputation (3.8% vs. 5.0%, odds ratio (OR): 0.83 [0.72-0.97], P = .018). Subgroup analysis revealed a higher mortality rate in OPEN was observed only in tibioperoneal intervention for tissue loss. Major adverse cardiovascular event was higher in OPEN for most subgroups. OPEN for patients with tissue loss had significantly lower amputation rate than ENDO in both femoropopliteal and tibioperoneal subgroups (3.7% vs. 5.1%, OR: 0.76 [0.59-0.98], P = .036, and 4.7% vs. 6.6%, OR: 0.74 [0.57-0.96], P = .024, respectively). The benefit of open surgery in reducing the amputation rate was not seen in patients with rest pain.
CONCLUSIONS: Open surgical intervention is associated with significantly better limb salvage than endovascular intervention in patients with tissue loss. Surgical options should be given more emphasis as the first-line option in this cohort of patients unless the cardiopulmonary risk is prohibitive.

A growing, but poorly defined subset of patients with chronic limb-threatening ischemia (CLTI) have \"no option\" for revascularization. One notable subgroup includes patients with severe ischemia and advanced pedal artery occlusive disease, termed \"desert foot,\" who are at high risk for major amputation due to a lack of conventional revascularization options. Although new therapies are being developed for no-option patients with desert foot anatomy, this subgroup and the broader group of no-option patients are not well defined, limiting the ability to evaluate outcomes. Based on a systematic review, a classification of the no-option CLTI patient was constructed for use in clinical practice and studies. Several no-option conditions were identified, including type I-severe and pedal occlusive disease (desert foot anatomy) for which there is no accepted method of repair; type II-lack of suitable venous conduit for bypass in the setting of an acceptable target for bypass; type III-extensive tissue loss with exposure of vital structures that renders salvage impossible; type IV-advanced medical comorbidities for which available revascularization options would pose a prohibitive risk; and type V-presence of a nonfunctional limb. While type I and type II patients may have no option for revascularization, type III and type V patients have wounds, infection, comorbidities, or functional status that may leave them with few options for revascularization. As treatment strategies continue to evolve and novel methods of revascularization are developed, the ability to identify no-option patients in a standardized fashion will aid in treatment selection and assessment of outcomes.

In animals that regularly experience tissue loss, physiological responses may have evolved to overcome the related costs. Changes in oxidative status may reflect such self-maintenance mechanisms. Here, we investigated how markers of oxidative status vary in female orb-weaving spiders (Larinia jeskovi) by mimicking two distinct types of tissue loss they may naturally encounter: damage to their locomotory system and damage to their external genital structure (scapus), as inflicted by males during copulation (external female genital mutilation). Damage to the locomotory system resulted in a significant shift in oxidative status, reflecting investment in self-maintenance. In contrast, the loss of the scapus did not result in quantitative changes of oxidative markers. This lack of a physiological response suggests negligible physiological costs of genital mutilation for female spiders. However, not being able to remate with other males might be costly for females.

The objective of this study was to determine predictors of increased length of stay (LOS) in patients who underwent lower extremity bypass for tissue loss.
Using 2011 to 2016 National Surgical Quality Improvement Program vascular targeted databases, we compared demographics, comorbidities, procedural characteristics, and 30-day outcomes of patients who had expected LOS vs extended LOS (>75th percentile, 9 days) after nonemergent lower extremity bypass for tissue loss. We also compared factors associated with short LOS (<25th percentile, 4 days) and extended LOS (>75th percentile, 9 days) vs the interquartile range of LOS (4-9 days). Yearly trends and independent predictors were determined by linear and logistic regression. This study was exempt from Institutional Review Board approval.
In 4964 analyzed patients, there were no significant yearly trends or changes in LOS in the recent 5 years (P > .05). Overall 30-day mortality, major amputation, and reintervention rates were 1.6%, 4.5%, and 4.8%, respectively, also with no significant yearly trends (all P > .05). On univariate analysis, nonwhite race, dependent functional status, transfers, dialysis, congestive heart failure, hypertension, beta blockers, distal bypass targets, and extended operative time were associated with extended LOS (P < .05). Extended LOS was also associated with higher rates of 30-day major adverse limb and cardiac events, additional procedures related to wound care, deep venous thrombosis, complications (pulmonary, renal, septic, bleeding, and wound), and discharge to facility but lower 30-day readmission rates. After adjustment for covariates, the independent factors for extended LOS included dialysis, beta blockers, prolonged operative time, reintervention, major amputation, additional procedures related to wound care, deep venous thrombosis, complications (pulmonary, renal, septic, bleeding, and wound), and discharge to facility (P < .05). On the other hand, multivariable analysis showed that patients with expected LOS were significantly more likely to have been of white race or readmitted postoperatively (P < .05).
From 2011 to 2016, there were no significant changes in LOS. Efforts to decrease LOS without increasing readmission rates while focusing on some of the identified factors, including preventable postoperative complications and pre-existing socioeconomic factors, may improve the overall vascular care of these challenging patients.

Skin wrinkling, especially in the facial area, is a prominent sign of aging and is a growing area of research aimed at developing cosmetics and dermatological treatments. To better understand and treat undesirable skin wrinkles, it is vitally important to elucidate the underlying mechanisms of skin wrinkling, a largely mechanical process. Human skin, a multi-layer composite, has six mechanically distinct layers: from the outermost inward they are the stratum corneum, viable epidermis, dermal-epidermal-junction, papillary dermis, reticular dermis, and hypodermis. To better address the through-thickness hierarchy, and the development of wrinkling within this complicated hierarchy, we established a six-layered model of human skin realized with finite element modeling, by leveraging available morphological and biomechanical data on human skin of the forehead. Exercising our new model we aimed to quantify the effects of three potential mechanisms of wrinkle formation: (1) skin compression due to muscle contraction (dynamic wrinkles); (2) age-related volumetric tissue loss (static wrinkles); and (3) the combined effects of both mechanisms. Since hydration of the stratum corneum significantly affects its stiffness we also aimed to quantify the influence its hydration with these three potential mechanisms of wrinkle formation. Our six-layered skin model, combined with the proposed wrinkling mechanisms, successfully predicts the formation of dynamic and static wrinkles in the forehead consistent with the experimental literature. We observed three wrinkling modes in the forehead where the deepest wrinkles could reach to the reticular dermis. With further refinement our new six-layered model of human skin can be applied to study other region-specific wrinkle types such as the \"crow\'s feet\" and the nasolabial folds.

The responses in growth and defense after tissue damage are highly variable in plants depending on species, damaged-tissue type and the intensity of damage. The prevailing abiotic conditions can also influence these responses. In this study, our aim was to examine how the removal of lateral vegetative buds affects the growth and accumulation of phenolics in saplings of the dioecious Populus tremula grown under simulated climate change. For three growing seasons, the saplings were grown under ambient conditions (control), elevated temperature (+2°C) and elevated UV radiation (30%) (UVB and UVA as its control), or a combination of these. In the fourth growing season, all saplings were grown under ambient conditions. The bud removal was performed twice - in summer and autumn - in the third year. The responses of growth and the accumulation of phenolics to the bud removal were measured at the end of the fourth growing season. Removal of 5% of the lateral buds resulted in higher leaf, stem and total plant biomass in both sexes of P. tremula saplings, compared to intact plants. The effects were greater in the temperature-treated plants, especially in the temperature-treated females. The concentrations of flavonoids and condensed tannins were higher in the bud-removed individuals. The concentration of condensed tannins was also higher in the males than in the females, opposite to the concentration of phenolic acids. There was no significant interaction between bud removal and UVB treatment on either growth or phenolics. Our results suggest that plants can allocate resources to both growth and defense simultaneously in response to tissue loss, and that global warming can modify the responses to some extent.