Chronic limb-threatening ischemia is defined as ischemic rest pain or tissue loss (eg, ulceration/gangrene) that has been present for greater than 2 weeks. Workup includes a careful history, physical examination focused on evaluation of pulses and wounds, lower extremity noninvasive vascular studies (eg, ankle-brachial indices, toe pressures), saphenous vein mapping, and imaging of the lower extremity arterial anatomy (eg, computed tomography, magnetic resonance, or subtraction angiography) if a revascularization intervention is planned.

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.

OBJECTIVE: Prior studies have described risk factors associated with amputation in patients with concomitant diabetes and peripheral arterial disease (DM/PAD). However, the association between the severity and extent of tissue loss type and amputation risk remains less well-described. We aimed to quantify the role of different tissue loss types in amputation risk among patients with DM/PAD, in the context of demographic, preventive, and socioeconomic factors.
METHODS: Applying International Classification of Diseases (ICD)-9 and ICD-10 codes to Medicare claims data (2007-2019), we identified all patients with continuous fee-for-service Medicare coverage diagnosed with DM/PAD. Eight tissue loss categories were established using ICD-9 and ICD-10 diagnosis codes, ranging from lymphadenitis (least severe) to gangrene (most severe). We created a Cox proportional hazards model to quantify associations between tissue loss type and 1- and 5-year amputation risk, adjusting for age, race/ethnicity, sex, rurality, income, comorbidities, and preventive factors. Regional variation in DM/PAD rates and risk-adjusted amputation rates was examined at the hospital referral region level.
RESULTS: We identified 12,257,174 patients with DM/PAD (48% male, 76% White, 10% prior myocardial infarction, 30% chronic kidney disease). Although 2.2 million patients (18%) had some form of tissue loss, 10.0 million patients (82%) did not. The 1-year crude amputation rate (major and minor) was 6.4% in patients with tissue loss, and 0.4% in patients without tissue loss. Among patients with tissue loss, the 1-year any amputation rate varied from 0.89% for patients with lymphadenitis to 26% for patients with gangrene. The 1-year amputation risk varied from two-fold for patients with lymphadenitis (adjusted hazard ratio, 1.96; 95% confidence interval, 1.43-2.69) to 29-fold for patients with gangrene (adjusted hazard ratio, 28.7; 95% confidence interval, 28.1-29.3), compared with patients without tissue loss. No other demographic variable including age, sex, race, or region incurred a hazard ratio for 1- or 5-year amputation risk higher than the least severe tissue loss category. Results were similar across minor and major amputation, and 1- and 5-year amputation outcomes. At a regional level, higher DM/PAD rates were inversely correlated with risk-adjusted 5-year amputation rates (R2 = 0.43).
CONCLUSIONS: Among 12 million patients with DM/PAD, the most significant predictor of amputation was the presence and extent of tissue loss, with an association greater in effect size than any other factor studied. Tissue loss could be used in awareness campaigns as a simple marker of high-risk patients. Patients with any type of tissue loss require expedited wound care, revascularization as appropriate, and infection management to avoid amputation. Establishing systems of care to provide these interventions in regions with high amputation rates may prove beneficial for these populations.

The IntegraⓇ Dermal Regeneration Template (DRT) is a bioengineered dermal substitute that is becoming increasingly popular in the field of reconstruction. Its unique properties allow for immediate wound closure while providing a scaffold for tissue regeneration. Currently, it is commonly used to treat burns, ulcers, and complex wounds. In the setting of traumatic periocular tissue loss, only two prior reports have been published on its use for primary reconstruction. We present our institution\'s experience with a series of four young patients who received primary reconstruction with IntegraⓇ DRT as a full-thickness skin substitute for their large traumatic periorbital skin defects.

Cholesterol crystal embolism (CCE) accompanied by a lower extremity wound is occasionally difficult to differentiate from chronic limb-threatening ischemia (CLTI) and treat. The present multi-center retrospective observational study investigated the clinical characteristics and prognosis of CCE with lower extremity wounds. Consecutive patients (n = 58) clinically diagnosed as CCE with lower extremity wounds between April 2010 and December 2019 were studied. CCE was diagnosed using histological findings, foot condition, renal impairment, and eosinophilia. The primary outcome was 1-year wound healing rate. Patients with CCE were compared with 1309 patients diagnosed with CLTI with tissue loss during the same study period. The CCE group had a significantly more severe Wound, Ischemia, and foot Infection (WIfI) classification compared with the CLTI group. After Kaplan-Meier analysis, the CCE group had a similar 1-year wound healing (55.1 vs 58.3%, P = .096) as the CLTI group. In multivariate stratified Cox regression analysis by WIfI stages, CCE was significantly associated with poor wound healing compared with CLTI [hazard ratio .36 (95% confidence interval .21-.62)]. In conclusion, among the similar WIfI clinical stages, wound healing was significantly worse in the CCE group than in the CLTI group.

Manganese (Mn) is an essential element and is generally considered to be one of the least toxic metals to aquatic organisms, with chronic effects rarely seen at concentrations below 1000 µg/L. Anthropogenic activities lead to elevated concentrations of Mn in tropical marine waters. Limited data suggest that Mn is more acutely toxic to adults than to early life stages of scleractinian corals in static renewal tests. However, to enable the inclusion of sufficient sensitive coral data in species sensitivity distributions to derive water quality guideline values for Mn, we determined the acute toxicity of Mn to the adult scleractinian coral, Acropora muricata, in flow-through exposures. The 48-h median effective concentration was 824 µg Mn/L (based on time-weighted average, measured, dissolved Mn). The endpoint was tissue sloughing, a lethal process by which coral tissue detaches from the coral skeleton. Tissue sloughing was unrelated to superoxidase dismutase activity in coral tissue, and occurred in the absence of bleaching, that is, toxic effects were observed for the coral host, but not for algal symbionts. We confirm that adult scleractinian corals are uniquely sensitive to Mn in acute exposures at concentrations 10-340 times lower than those reported to cause acute or chronic toxicity to coral early life stages, challenging the traditional notion that early life stages are more sensitive than mature organisms. Environ Toxicol Chem 2023;42:1359-1370. © 2023 Commonwealth Scientific and Industrial Research Organisation. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

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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.

BackgroundRevascularisation of patients with chronic limb threatening ischaemia due to arterial lesions in the below the knee segment can be challenging. This study describes a novel technique that allows a complete endovascular reconstruction of the trifurcation (CERT) utilising stents in the below the knee segment when conventional techniques are exhausted, or have failed to deliver an acceptable result, leading to remaining outflow compromise. Methods: Eight patients with Rutherford 5 chronic limb threatening ischaemia underwent CERT between January 1st, 2018 and January 1st, 2020. All patients underwent ultrasound at 6 weeks post operatively and then at variable intervals until the completion of the follow up period in March 2020. Results: Technical success of the CERT technique was achieved in all patients. Six patients had anterior tibial artery/Tibioperoneal trunk reconstructions, whilst 2 patients were stented directly into posterior tibial and peroneal artery. Five patients (63%) achieved wound healing. All-cause mortality was 25% (2 patients) with 1 patient achieving wound healing prior to death. Two stents were occluded during the follow up period. The first was asymptomatic and had achieved wound healing. The second was symptomatic with stent occlusion and a delayed presentation with Rutherford 3 acute limb ischaemia. Conclusions: Complete endovascular reconstruction of the trifurcation is a feasible option to achieve revascularisation in patients with tissue loss and below the knee arterial lesions allowing a continuous reconstruction of the trifurcation segment keeping the anatomical configuration intact. Clinical outcomes appear acceptable however larger series are needed.

Critical limb ischemia (CLI) is an entity with high mortality if not properly treated. The primary aim of CLI revascularization is to enhance wound healing, which greatly depends on microvascular circulation. The available tools for assessment of revascularization success are deficient in the evaluation of local microvascular tissue perfusion, that wound blush (WB) reflects. A reliable technique that assesses capillary flow to foot lesions is needed. This study aims to assess WB angiographically at sites of interest in the foot after revascularization and its impact on limb salvage in CLI.
198 CLI patients (Rutherford category 5/6) with infrainguinal atherosclerotic lesions amenable for endovascular revascularization (EVR) were included. Limbs were directly or indirectly revascularized by EVR. Direct revascularization meant that successful revascularization of the area of interest according to the angiosome concept was achieved. A completion angiographic run was taken to assess WB. Patients were divided into 2 groups; positive and negative WB groups. In the event of a disagreement between the observational investigators, the digital subtraction angiography (DSA) series was analyzed for hemodynamic changes with a computerized 2D color-coded DSA (Syngo iFlow).
176 limbs had successful revascularization in 157 patients. The successful revascularization rate was 88.9% (176/198), with technical failure encountered in 22 limbs. 121 patients had positive WB and 55 patients had negative WB. Direct revascularization of target areas was obtained in 98 limbs (55.7%). There was a significant difference in the rate of achieving direct flow to the lesion between the positive WB and negative WB groups (36.4% vs 19.3%, p≤0.001). We noticed a nonsignificant difference between patients who had direct revascularization of the foot lesion(s) and those who had indirect revascularization as regards limb salvage. Patients were followed up for 25.2 ± 12.7 months. By the end of the first year, limb salvage rate was significantly higher in patients who had positive WB (98% vs 63%, p<0.001, after 2 years (97% vs 58%, p<0.001) and after 3 years (94% vs 51.5%, p<0.001).
WB is an important predictor and a prognostic factor for wound healing in CLI patients with soft tissue lesions.