Lower Extremity Ulcers Research Articles

Putting skin in the game: a descriptive study of lower extremity ulcers in general medical inpatients.

Lower extremity ulcers contribute a significant burden to patient care. Targeted investigation and management are pertinent to improving patient outcomes. We evaluated the aetiology, risk factors, investigations and management of lower extremity ulcers in general medicine patients. There was evidence of under-ordering of appropriate investigations, and over-treatment for infection. We proposed a quality improvement initiative to optimise lower extremity ulcer care.

Effective Management of Chronic Lower-Extremity Ulcers (CLEU) by Fu’s Subcutaneous Needling (FSN)

Effective Management of Chronic Lower-Extremity Ulcers (CLEU) by Fu’s Subcutaneous Needling (FSN)

COVID-19 and COVID-19 Vaccine-Related Skin Ulcerations in the Lower Extremities: A Case Report and Literature Review

Several associations have been made between COVID-19 and vasculitis. Recent data also shows the prevalence and association of de novo vasculitis with either COVID-19 infection or COVID-19 post vaccination. In this article, we present the case of new-onset leukocytoclastic vasculitis, secondary to COVID-19 vaccination, that was complicated by severe infected and nonhealing ulcers in the lower extremities. Case A 53-year-old male patient presented to the dermatology clinics with a three-week history of painful necrotic patches coalescent of the lateral malleolus of the right and left ankles. History goes back to when the patient reported developing pruritic papules two weeks after receiving his second shot of the Pfizer BioNTech COVID-19 vaccine (BNT162b2). Punch biopsy was consistent with leukocytoclastic vasculitis. He was prescribed a four-week course of systemic corticosteroids and antibiotics as per cultures. Vascular assessment confirmed normal peripheral arterial and venous system. Two months later, the patient re-presented with fever and worsening of his lower extremity ulcers. He underwent debridement of his wounds. Intra-operative cultures revealed multidrug resistant bacteria. He required an additional debridement session a few days later and a 14-day course of Piperacillin-Tazobactam. The patient was subsequently discharged on corticosteroids and Azathioprine and followed up in the vascular surgery and rheumatology clinics. At four months follow-up, the patient's wounds were almost completely healed. Conclusion This article highlights a case of severe new-onset COVID-19 vaccine-associated leukocytoclastic vasculitis complicated with infected ulcers that required debridement twice in addition to a prolonged course of antibiotics and immunosuppression therapy. To our knowledge, none of the cases reported in the literature were this severe in nature. In this post-pandemic era, it must remain high on the differential list, and healthcare specialists should maintain a high index of suspicion when evaluating sudden new-onset skin lesions that do not have an immediately apparent etiology.

Usefulness of hot shot intermittent infusion online hemodiafiltration plus far-infrared therapy for dialysis patients with lower extremity arterial disease: a case report

BackgroundLower extremity arterial disease (LEAD) occurs at a high frequency in dialysis patients and is associated with a poor prognosis. In recent years, intermittent infusion online hemodiafiltration (I-OHDF) combined with far-infrared therapy (FIR) has been reported as being useful in dialysis patients with LEAD. However, there are also reports of worsening of the ulcers and gangrene in some cases. Hot shot I-OHDF (HS I-OHDF), which involves intermittent infusion of heated dialysate, is reported as being more effective than conventional I-OHDF for improving the plasma refilling rate (PRR) and peripheral circulation. We report the case of a patient in whom a lower extremity ulcer healed only after we switched from I-OHDF + FIR to HS I-OHDF + FIR, and the usefulness of this treatment.Case presentationThe patient was a 41-year-old male dialysis patient with LEAD who showed worsening of the ulcers in the lower extremity before he was switched from I-OHDF plus FIR to HS I-OHDF plus FIR; we compared the changes in the lower extremity blood flow, PRR, degree of wound healing, and subjective symptoms over time after the switch to HS I-OHDF plus FIR as compared with the values prior to the switching. As compared with the values during I-OHDF plus FIR, the lower extremity blood flow and PRR increased markedly during HS I-OHDF plus FIR. The wounds in the lower extremity improved over time during HS I-OHDF plus FIR and showed complete healing after 6 months; evaluation by visual analog scales (VASs) showed improved scores for all of fatigue, pain, coldness, and insomnia, and the patient reported improved subjective symptoms. The mechanism underlying the effectiveness of HS I-OHDF plus FIR in promoting wound healing is unknown, however, we speculated that the temperature change in the intermittent infusion solution resulted in increased blood flow in the true capillaries (resting vessels) and transfer of the nonthermal effects of FIR to more peripheral vessels.ConclusionsThis case demonstrates that combined use of HS I-OHDF with FIR can enhance the efficacy of FIR in dialysis patients with LEAD by increasing the lower extremity blood flow and PRR, which is useful for wound healing.

Successful treatment of pyoderma gangrenosum with guselkumab

AbstractGuselkumab, a monoclonal antibody known for its effective inhibition of T‐cell‐immunoactivity through specific binding to interleukin‐23 (IL‐23)‐cytokines, may be used for off‐label treatment of pyoderma gangrenosum (PG). Herein, we report two successful cases of off‐label treatment for PG, using guselkumab, after unsuccessful treatments with standard regimens of corticosteroids, immunomodulating therapy and other biological agents. Case 1 involves a 39‐year‐old female with treatment‐resistant peristomal PG post‐colectomy and ileostomy. Case 2 features a 35‐year‐oldfemale with treatment‐resistant PG, presenting with deep necrotic lower extremity ulcers. In both cases, we observed remarkable healing within months to a year. These two cases support the potential use of systemic IL‐23‐targetedtherapy for treatment‐resistant PG.

Association Between red Cell Distribution Width/Albumin Ratio and Diabetic Lower Extremity Ulcers (DLEU) among US Outpatients in the NHANES: A Retrospective Cross-Sectional Study.

Diabetic foot ulcers are common chronic complications of diabetes mellitus that can lead to amputation and death in severe cases. There is limited research on the relationship between the red cell distribution width/albumin ratio and diabetic lower-extremity ulcers. The few studies that have been conducted have been in single-center inpatient settings and there is limited research in outpatient settings. This study investigated this relationship in adult outpatient clinics in the United States. A retrospective cross-sectional study was conducted with 1624 participants of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. Three logistic regression models were developed to assess the association between red cell distribution width/albumin ratio and diabetic lower-extremity ulcers. The ratio was analyzed as a continuous and categorical variable. Stratified analyses were performed based on age, sex, HbA1c level, and body mass index. The study included 1624 adults, with a mean age of 65.0 ± 12.0 years, of whom 58.8% were male. The prevalence of diabetic lower-extremity ulcers was 8.0% (n = 131). Compared with individuals with a lower red cell distribution width/albumin ratio in T1(2.32,2.93), the adjusted OR values for the ratio and ulcers in T2(2.94,3.26), T3(3.27,7.42), and 2.07 (95% CI = 1.19∼3.61), 2.92 (95% CI = 1.63∼5.23). The association between the ratio and ulcers exhibited a non-linear relationship (nonlinear, P = .028). These results support the hypothesis of an S-shaped relationship between red cell distribution width/albumin and diabetic lower-extremity ulcers. Monitoring the RDW/Albumin ratio could be crucial for preventing diabetic lower-extremity ulcers in outpatient settings. Regular assessments may help identify high-risk patients early, enabling timely interventions. Future studies should further assess these two factors and their underlying mechanisms.

Treatment of bacterially contaminated lower extremity ulcers with a fatty acid-containing wound matrix: a case series.

The aim was to evaluate the effectiveness of a marine omega fatty acid-containing multimodal wound matrix (MWM) in reducing bacterial contamination and supporting wound area reduction (WAR) in patients with hard-to-heal wounds of varying aetiologies. A prospective, single-site, pilot case series of patients with hard-to-heal wounds. All wounds were considered non-healing prior to inclusion as they had failed to achieve at least 50% WAR after at least four weeks of standard of care (SoC) treatments. Patients were seen once weekly for wound assessments, matrix application and dressing changes. Baseline and weekly fluorescence images, standard wound images and wound measurements were obtained. A total of three patients, two with venous leg ulcers (VLUs) and one with a diabetic foot ulcer (DFU) were enrolled in this pilot study. The mean baseline wound age prior to study enrolment was 24 weeks, with a mean baseline wound size of 8.61cm2. The two VLUs went on to complete closure. The DFU displayed a total WAR of 53% by six weeks, when the patient was lost to follow-up due to a geographical relocation. The mean percentage area reduction of all wounds combined was 82% upon study completion. The use of MWM proved to be effective and safe in this patient cohort. The wounds included in this case series failed to enter a healing trajectory with SoC wound therapies. The MWM supported wound closure and reduced bacterial loads in this patient cohort.

Discrepancy in opioid prescription patterns for Black or African American patients following lower extremity bypass surgery for chronic limb-threatening ischemia

BackgroundDisparity in the allocation of medical services and resources based on race is present within the health care industry today, including the prescription of postoperative analgesics. The purpose of this study was to evaluate the presence of race-based disparity in the prescription of postdischarge opioids after lower extremity bypass (LEB) surgery for chronic limb-threatening ischemia (CLTI). MethodsRetrospective analysis was conducted on adult CLTI patients who underwent LEB from 2000 to 2023 in the TrinetX database. Patients were stratified into two groups based on race: White (group I) and black or African American (AA) (group II). Primary outcomes were defined as oral opioid prescriptions at 7 days and 30 days after discharge, and mortality at 1 year postoperatively. Secondary outcomes included length of stay and 30-day postoperative outcomes, including myocardial infarction, pulmonary embolism, cerebral vascular accident, deep vein thrombosis, acute kidney injury, major amputation, minor amputation, major adverse cardiac events, and major adverse limb events. Stratified analysis was conducted based on disease stage (rest pain vs lower extremity ulcer vs gangrene). Univariate analysis was performed via two-sample t test and χ2 test. Logistic regression was performed to estimate the association of Black or AA (vs White) race while controlling for pertinent preoperative potential confounders. ResultsThere were 3345 patients who met the inclusion criteria. Group I included 2661 White patients and group II included 684 Black or AA patients. Group II patients were more likely to be younger, female, present with gangrene, and have a history of hypertension, diabetes, chronic kidney disease, or diabetic neuropathy. At both 7 and 30 days after discharge, the Black or AA cohort had significantly lower rates of opioid prescriptions (33.2% vs 42.5% and 35.8% vs 47.2%, respectively) (all P < .05). Stratification by indication showed that opioid prescription disparity persisted despite black or AA patients presenting at worse stages of disease both at 7 and 30 days after discharge (7 days: rest pain 43.4% vs 33.7% [P = .013], ulcer 41.4% vs 31.7% [P = .027], gangrene, 42.7% vs 33.6% [P = .006] and 30 days: rest pain 47.8% vs 37.1% [P = .007], ulcer 45.4% vs 33.5% [P = .007], gangrene, 48.2% vs 36.1% [P < .001]). Adjusted analysis confirmed that Black or AA race was associated with lower rates of 7- (adjusted odds ratio, 0.607; P = .001) and 30-day (adjusted odds ratio, 0.56; P = .001) postdischarge opioid prescriptions. ConclusionsBlack or AA patients were less likely to receive postdischarge opioid prescriptions compared with their White counterparts at 7 and 30 days after LEB for CLTI.

Assessment of potential genetic markers for diabetic foot ulcer among Moscow residents.

Diabetic foot ulcer (DFU) is one of the most severe complications of type 2 diabetes, which is manifested in chronic skin ulcers of lower extremities. DFU treatment remains complex and expensive despite the availability of well-established protocols. Early prediction of potential DFU development at the onset of type 2 diabetes can greatly improve the aftermath of this complication. To assess potential genetic markers for DFU, a group of diabetic patients from Moscow region with and without DFU was genotyped for a number of SNPs previously reported to be associated with the DFU. Obtained results did not confirm previously claimed association of rs1024611, rs3918242, rs2073618, rs1800629, rs4986790, rs179998, rs1963645 and rs11549465 (respectively, in MCP1, MMP9, TNFRSF11B, TNFα, TLR4, eNOS, NOS1AP and HIF1α genes) with the DFU. Surprisingly, the t allele of rs7903146 in the TCF7l2 gene known as one of the most prominent risk factors for type 2 diabetes has shown a protective effect on DFU with OR(95%) = 0.68(0.48-0.96). Non-replication of previously published SNP associations with DFU suggests that the role of genetic factors in the DFU onset is either highly variable in different populations or is not as significant as the role of non-genetic factors.

Effects of Recombinant Human Granulocyte/Macrophage Colony-Stimulating Factor on Diabetic Lower Extremity Ulcers: Case Series of Nine Patients [Response to Letter

Effects of Recombinant Human Granulocyte/Macrophage Colony-Stimulating Factor on Diabetic Lower Extremity Ulcers: Case Series of Nine Patients [Response to Letter

Effects of Recombinant Human Granulocyte/Macrophage Colony-Stimulating Factor on Diabetic Lower Extremity Ulcers: Case Series of Nine Patients [Letter

Effects of Recombinant Human Granulocyte/Macrophage Colony-Stimulating Factor on Diabetic Lower Extremity Ulcers: Case Series of Nine Patients [Letter

Comparative Effectiveness of Placental Allografts in the Treatment of Diabetic Lower Extremity Ulcers and Venous Leg Ulcers in U.S. Medicare Beneficiaries: A Retrospective Observational Cohort Study Using Real-World Evidence.

Objective: To compare the effectiveness of cellular tissue products (CTP) versus standard care in U.S. Medicare beneficiaries with diabetic lower extremity ulcers (DLEUs) or venous leg ulcers (VLUs). Approach: We performed a retrospective cohort study using real-world evidence from U.S. Medicare claims for DLEUs or VLUs between 2016 and 2020. There were three cohorts evaluated: viable cryopreserved placental membrane (vCPM) or viable lyopreserved placental membrane (vLPM); other CTP; and standard care. Claims were collapsed into episodes of care. Univariate and bivariate statistics were used to examine the frequency distribution of demographics and clinical variables. Multivariable zero-inflated binomial regressions were used to evaluate mortality and recurrence trends. Logistic regression compared three adverse outcomes (AOs): amputation; 1-year mortality; and wound recurrence. Results: There were 333,362 DLEU episodes among 261,101 beneficiaries, and 122,012 VLU episodes among 80,415 beneficiaries. DLEU treatment with vLPM was associated with reduced 1-year mortality (-26%), reduced recurrence (-91%), and reduced AOs (-71%). VLU treatment with vCPM or vLPM was associated with reduced 1-year mortality (-23%), reduced recurrence (-80%), and 66.77% reduction in AOs. These allografts were also associated with a 49% and 73% reduced risk of recurrence in DLEU and VLU, respectively, compared with other CTPs. Finally, vCPM or vLPM were associated with noninferior prevention of AOs related to amputation, mortality, and recurrence (95% CI: 0.69-1.14). Conclusions: DLEUs and VLUs treated with vCPM and vLPM allografts are associated with lowered 1-year mortality, wound recurrence, and AOs in DLEUs and VLUs compared with standard care. Decision makers weighing coverage of placental allografts should consider these added short- and long-term clinical benefits relative to costly management and high mortality of Medicare's most frequent wounds.

Epidemiological profile of patients with chronic lower extremity ulcers in two public hospitals in southern Brazil

Epidemiological profile of patients with chronic lower extremity ulcers in two public hospitals in southern Brazil

Prevalence and characteristics of pain in patients with lower-extremity ulcers-A cross-sectional study.

The study aimed to investigate the prevalence and characteristics of pain in different ulcer types and to identify factors associated with pain experience in patients with lower-extremity ulcers. A cross-sectional single-centre study was performed, including 130 newly referred outpatients with lower-extremity ulcers. Pain intensity was measured with a visual analog scale (VAS) and pain characteristics with the short form mcgill pain questionnaire-2 (SF-MPQ-2). The mean pain intensity was 29.5 (SD 31.8) at rest and 35.5 (SD 34.1) during movement (0-100 VAS). 61.5% of the patients experienced pain (VAS > 0) at rest and 70.8% during movement. Moderate to severe pain at rest was seen in 39.2% and in 43.8% of patients during movement. The mean total score on SF-MPQ-2 (range 0-220) was 35.9 (SD 32.6). Most of the patients described pain as intermittent (mean 11.8 SD 13.9). Analgesics were prescribed for 78% of the patients. Ulcer type (i.e., arterial, immunological, pressure and venous) and age were associated with pain severity, and women had a significantly lower well-being score than men. Prevalence of pain in patients with lower-extremity ulcers was high across different ulcer aetiologies. Pain intensity and quality must be assessed to obtain adequate pain management.

'Patera syndrome' during the COVID-19 pandemic in the Canary Islands (Spain).

The number of migrants arriving on the shores of the Canary Islands continues to increase. The conditions under which the crossing is made, in small crowded, unsanitary boats (pateras or cayucos), have many and significant health problems. To describe the demographic, clinical, microbiological characteristics and evolution of a series of patients who recently arrived by patera and required hospitalization. This observational, cross-sectional, and retrospective study included all patients newly arrived in Gran Canaria (Spain) by patera or cayuco from 2020 to 2022. Acute patera syndrome (APS) was defined as one or more of the following: dehydration, hypothermia, shock or rhabdomyolysis. Skin and soft tissue or musculoskeletal patera syndrome (SSTMSPS) was defined as conditions characterized by lesions of the skin, subcutaneous tissue, bone, or joint, excluding superficial erosions. During the study period, 193 migrants were admitted, mostly males with a median age of 23 years from West Africa. A total of 36.99% presented with APS with a single diagnostic criterion (most commonly dehydration, 86.9%), 11.56% with SSTMPS and 51.44% with both syndromes. A total of 109 patients presented with SSTMSPS, the most common being lower extremity ulcers. The most frequently isolated microorganisms were gram-negative (i.e. Shewanella algae). The McMahon score effectively predicted the need for renal replacement therapy in cases of rhabdomyolysis. Twenty patients presented with pneumomediastinum, which was benign. SARS-CoV-2 infection was not a problem in any of them. Surgical intervention was required in 22% of cases, including 8 amputations, all of which were minor. No patient died during admission. Patera syndrome has specific characteristics that should be identified promptly to initiate the most effective treatment for optimal outcomes.

Association between anemia and diabetic lower extremity ulcers among US outpatients in the National Health and Nutrition Examination Survey: a retrospective cross-sectional study.

The aim of this study was to explore the relationship between hemoglobin levels, anemia and diabetic lower extremity ulcers in adult outpatient clinics in the United States. A retrospective cross-sectional study was conducted on 1673 participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. Three logistic regression models were developed to evaluate the relationship between anemia and diabetic lower extremity ulcers. Model 1 adjusted for demographic and socioeconomic variables (age, sex, race and ethnicity, educational level, family income, and marital status). Model 2 included additional health-related factors (BMI, cardiovascular disease, stroke, family history of diabetes, hyperlipidemia, alcohol and smoking status). Model 3 further included clinical and laboratory variables (HbA1c, CRP, total cholesterol, and serum ferritin levels). Stratified analyses were also conducted based on age, sex, HbA1c level, body mass index (BMI), and serum ferritin level. The study included 1673 adults aged 40 years and older, with a mean age of 64.7 ± 11.8 years, of whom 52.6% were male. The prevalence of diabetic lower extremity ulcers (DLEU) was 8.0% (136 participants). Anemia was found in 239 participants, accounting for 14% of the study group. Model 1 showed an OR of 2.02 (95% CI=1.28~3.19) for anemia, while Model 2 showed an OR of 1.8 (95% CI=1.13~2.87). In Model 3, the OR for DFU in patients with anemia was 1.79 (95% CI=1.11~2.87). Furthermore, when serum ferritin was converted to a categorical variable, there was evidence of an interaction between DLEU status and serum ferritin in increasing the prevalence of DLEU. After adjusting for confounding variables, higher levels of anemia were proportionally associated with an increased risk of incident DLEU. These results suggest that monitoring T2DM patients during follow-up to prevent the development of DLEU may be important. However, further prospective studies are needed to provide additional evidence.

Treating chronic wounds in an acute care setting: the forgotten diagnosis.

Chronic wounds include lower extremity ulcers, diabetic foot ulcers, and pressure injuries, and can take months or years to heal. Wounds place a high burden on outpatient and inpatient care settings. This burden is expected to increase markedly in the United States as the population ages and with increased rates of diabetes, obesity, and COVID-19. To articulate the effect of chronic, hard-to-heal wounds on acute care facilities, and how a few days of inpatient care can have a significant effect on the healing trajectory. An expert panel of 7 members, all with extensive knowledge and experience in the assessment and treatment of chronic wounds in an acute care setting, was convened in March 2022. The panel discussed the role of hospitals as part of the longer-term healing pathway of chronic wounds. Chronic wounds have a significant effect on hospitals that includes unseen costs, bed occupancy, demands on bedside nurses, and wound complications that lead to extended stays or readmissions. A successful inpatient wound program offers appropriate identification of previously undiagnosed wounds, elevation of bedside care through simplified protocols, quickly and easily understood education and easy dressing selection, and comprehensive discharge planning with a multidisciplinary team for continuity of care and reduced risk of readmission. Hospitals can play a key role in the management of chronic wounds, thus reducing the effect on each facility and the wider care network.

Chronic wounds of the lower limbs: a guide for non-specialists

Chronic lower-extremity ulcers are a growing public health problem, resulting in significant costs for society and patients, and having a significant impact on the quality of life of patients and informal caregivers. As general practitioners are often solicited early on, the acquisition of basic knowledge regarding wound care management is therefore essential to initiate local care, to make an early diagnosis and identify emergencies and patients that need a referral. The CASE and TIMERS frameworks enable a holistic assessment of the patient and the wound, to propose a treatment of the wound based on its etiology combined with appropriate local wound care. This framework allows also to identify atypical, severe, or recalcitrant wounds requiring specialized advice.

Myeloproliferative Neoplasms Are Associated with Increased Risk of Major Adverse Limb Events Among Patients Hospitalized for Peripheral Arterial Disease

Background: Myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are at high risk of cardiovascular (CV) disease, including atherosclerosis and peripheral arterial disease (PAD). Major adverse limb events (MALE), including major amputation, are dreaded complications of PAD that portend poor prognosis. Among patients with MPN, arterial thrombotic events are common and prior studies suggest that PAD is a risk factor for arterial thrombosis in this patient population. However, there are limited data on outcomes of patients with MPN and PAD. Therefore, the effect of MPN status on MALE, in-hospital death and unplanned readmissions among patients hospitalized for PAD. Methods: This was a retrospective cohort analysis of the National Readmission Database (NRD) of adult patients with a primary diagnosis of PAD from 2017 and 2018 with or without a history of MPN, as identified by ICD-10 codes. Primary outcome was MALE which was a composite of index hospitalization death, major amputation, 30-day readmission for PAD, lower extremity ulceration, gangrene, rest pain, major amputation or arterial thromboembolism. Secondary outcomes were bleeding complications at index hospitalization (including gastrointestinal, intracranial, post-procedure, and retroperitoneal bleeding), 90-day readmissions for any-cause, PAD, CV reason (including PAD, myocardial infarction, stroke, or heart failure), and bleeding. Propensity scores (PS) for estimating probability of MPN were calculated using non-parsimonious multivariable logistic regression that included all baseline patient characteristics examined. PS matching (PSM) 1 MPN case to 5 non-MPN controls was performed. Patients between groups were compared and standardized mean difference (SMD) was calculated for variables before and after PSM. Imbalances between groups were insignificant if SMD for a given co-variable was &amp;lt; 0.10. Odds ratio (OR) for MALE and in-hospital outcomes were calculated using logistic regression. For 90-day readmission analyses, patients who died during index hospitalization were excluded and hazard ratios (HR) were estimated using Cox proportional hazards regression. Risk factors for MALE among patients with MPN were assessed using backward stepwise logistic regression. Results: After PSM, 1702 patients with MPN (1338 ET, 273 PV, 91 PMF) were matched with 8510 non-MPN patients. After PSM, variables were well-balanced between patients with and without MPN, Table. MPN was associated with increased risk of MALE (40.3% vs 27.9%, OR 1.75, 95% CI 1.57 - 1.95) and major amputation at index hospitalization (34.6% vs 23.5%, OR 1.72, 95% CI 1.54 - 1.92) but not in-hospital death (1.8% vs 2.0%, OR 0.92, 95% CI 0.63 - 1.36) or bleeding (17.5% vs 19.5%, OR 0.90, 95% CI 0.79 - 1.03). MPN was associated with increased risk of 90-day readmission for any-cause (HR 1.21, 95% CI 1.10 - 1.33), PAD (HR 1.22, 95% CI 1.11 - 1.35), and CV reason (HR 1.32, 95% CI 1.17 - 1.49) but not for bleeding (HR 1.33, 95% CI 0.90 - 1.97), Figure. Among patients with MPN, ET (OR 2.08, 95% CI 1.44 - 3.01), end-stage renal disease (OR 1.59, 95% CI 1.12 - 3.11), anemia (OR 1.75, 95% CI 1.39 - 2.21), gangrene (HR 1.95, 95% CI 1.38 - 2.75), and sepsis (OR 1.90, 95% CI 1.36 - 2.66) were associated with increased risk of MALE while compared surgical bypass (OR 0.46, 95% CI 0.31 - 0.68) and endovascular revascularization (OR 0.71, 95% CI 0.54 - 0.94) during index hospitalization were associated with decreased risk of MALE. Conclusions: Among patients hospitalized for PAD, MPN was associated with increased risk of MALE and 90-day readmission for any-cause, PAD, and CV reasons. Among patients with MPN, ET was associated with increased risk of MALE while revascularization during index hospitalization was associated with decreased risk. Further studies are needed to further elucidate risk of MALE and adverse CV events among patients with MPN in order to improve clinical outcomes in this high-risk patient population.

Adipose-derived Mesenchymal Stem Cells are Ideal for the Cell-based Treatment of Refractory Wounds: Strong Potential for Angiogenesis.

Although Mesenchymal Stem Cells (MSCs)-based therapy has been proposed as a promising strategy for the treatment of chronic lower-extremity ulcers, their optimal sources, amounts, and delivery methods are urgently needed to be determined. In this study, we compared the heterogeneity of the human MSCs derived from bone marrow (BMSCs), umbilical cord (UCMSCs), and adipose tissue (ADSCs) in accelerating wound healing and promoting angiogenesis and explored the underlying mechanism. Briefly, a diabetic rat model with a full-thickness cutaneous wound on the dorsal foot was developed. The wound was topically administered with three types of MSCs. Additionally, we carried out in vitro and in vivo analysis of the angiogenic properties of the MSCs. Moreover, the molecular mechanism of the heterogeneity of the MSCs derived from the three tissues was explored by transcriptome sequencing. When compared with the BMSCs- and UCMSCs-treated groups, the ADSCs-treated group exhibited markedly accelerated healing efficiency, characterized by increased wound closure rates, enhanced angiogenesis, and collagen deposition at the wound site. The three types of MSCs formed three-dimensional capillary-like structures and promoted angiogenesis in vitro and in vivo, with ADSCs exhibiting the highest capacity for tube formation and pro-angiogenesis. Furthermore, transcriptome sequencing revealed that ADSCs had higher expression levels of angiogenesis-associated genes. Our findings indicate that MSCs-based therapy accelerates the healing of ischemia- and diabetes-induced lower-extremity ulcers and that adipose tissue-derived MSCs might be ideal for therapeutic angiogenesis and treatment of chronic ischemic wounds.