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Stem Cells Translational Medicine May 2021For patients with angiitis-induced critical limb ischemia (AICLI), cell transplantation, such as purified CD34 cells (PCCs) and peripheral blood mononuclear cells... (Randomized Controlled Trial)
Randomized Controlled Trial
Three-year outcomes of peripheral blood mononuclear cells vs purified CD34 cells in the treatment of angiitis-induced no-option critical limb ischemia and a cost-effectiveness assessment: A randomized single-blinded noninferiority trial.
For patients with angiitis-induced critical limb ischemia (AICLI), cell transplantation, such as purified CD34 cells (PCCs) and peripheral blood mononuclear cells (PBMNCs), is gradually being used as a promising treatment. This was the first randomized single-blinded noninferiority trial (number: NCT02089828) specifically designed to evaluate the therapeutic efficacies of the transplantation of PCCs vs those of PBMNCs for the treatment of AICLI. We aimed to compare the mid-term safety and efficacy between the two groups and determine their respective advantages. From April 2014 to September 2019, 50 patients with AICLI were equally allocated to the two groups, except for 1 lost patient, 1 amputee, and 1 patient who died of heart disease. The other 47 patients completed the 36-month follow-up. The endpoints were as follows: major amputation-free survival and total amputation-free survival at 6 months, which were 96.0% and 84.0% in the PBMNCs group and 96.0% and 72.0% in the PCCs group, respectively. These rates remained stable at 12, 24, and 36 months. The PCCs group had a significant higher probability of rest pain relief than the PBMNCs group, whereas earlier significant improvements in the Rutherford classification were observed in the PBMNCs group. Accordingly, PCCs would be preferred for patients with significant pain, whereas PBMNCs may be a good option for patients with two or more critically ischemic limbs. Concerning cost-effectiveness, PCCs are not more cost-effective than PBMNCs. These outcomes require verification from long-term trials involving larger numbers of patients.
Topics: Chronic Limb-Threatening Ischemia; Cost-Benefit Analysis; Humans; Ischemia; Leukocytes, Mononuclear; Pain; Treatment Outcome; Vasculitis
PubMed: 33399273
DOI: 10.1002/sctm.20-0033 -
JACC. Cardiovascular Interventions Sep 2021
Topics: Hospitals; Humans; Ischemia; Peripheral Arterial Disease; Treatment Outcome; Vascular Surgical Procedures
PubMed: 34503744
DOI: 10.1016/j.jcin.2021.07.037 -
European Journal of Vascular and... Feb 2020
Topics: Humans; Ischemia; Peripheral Vascular Diseases; Vascular Surgical Procedures
PubMed: 32029196
DOI: 10.1016/j.ejvs.2020.01.001 -
International Angiology : a Journal of... Dec 2021A pro-inflammatory state and a poor nutritional status have been associated with severity and prognosis of patients with peripheral arterial disease (PAD). The clinical... (Observational Study)
Observational Study
BACKGROUND
A pro-inflammatory state and a poor nutritional status have been associated with severity and prognosis of patients with peripheral arterial disease (PAD). The clinical applicability of the different pre-operative nutritional and inflammatory biomarkers in patients with critical limb-threatening ischemia (CLTI) was analyzed.
METHODS
A retrospective observational study was performed, that included all patients with CLTI revascularized from January 2016 to July 2019. The inflammatory state was calculated using neutrophil/lymphocyte (NLR), lymphocyte/monocyte (LMR) and platelet/lymphocyte ratios (PLR). For nutritional status, the Prognostic Nutritional Index (PNI) was calculated. Mortality and number of major amputations at 6 months and hospital length-of stay were studied.
RESULTS
310 patients were included. Higher levels of NLR and lower levels of PNI were associated with mortality (6.61±5.6 vs. 3.98±3.27, P=0.034; 40.33±7.89 vs. 45.73±7.48, P=0.05, respectively). Lower levels of PNI and LMR (42.57±7.82 vs. 45.44±7.65, P=0.036; 2.77±1.61 vs. 3.22±1.75, P=0.013, respectively) and higher levels of NLR (6.91±7.85 vs. 3.94±2.57, P=0.023) were associated with major amputations. The mean hospital length-of-stay was higher in patients with lower levels of PNI and LMR (P=0.000 and P=0.003) and higher levels of NLR and PLR (P=0.001 and P=0.002). A PNI<42.87 predicted short-term mortality with a 66.7% of sensitivity and a 66.8% of specificity (P=0.000).
CONCLUSIONS
Our experience suggests that these inflammatory and nutritional biomarkers are independent predictors of short-term mortality and major amputations. In addition, our results suggest that PNI could be used to predict the short-term mortality with high sensitivity and specificity.
Topics: Humans; Ischemia; Lymphocytes; Neutrophils; Nutrition Assessment; Prognosis; Retrospective Studies
PubMed: 34636508
DOI: 10.23736/S0392-9590.21.04739-8 -
Journal of Vascular Surgery Feb 2020Patients presenting with chronic limb-threatening ischemia and diabetic foot ulceration (DFU) are at high risk of major lower limb amputation. Long-standing concern...
OBJECTIVE
Patients presenting with chronic limb-threatening ischemia and diabetic foot ulceration (DFU) are at high risk of major lower limb amputation. Long-standing concern exists regarding late presentation and delayed management contributing to increased amputation rates. Despite multiple guidelines existing on the management of both conditions, there is currently no accepted time frame in which to enact specialist care and treatment. This systematic review aimed to investigate potential time delays in the identification, referral, and management of both chronic limb-threatening ischemia and DFU.
METHODS
A systematic review conforming to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards was performed searching MEDLINE, Embase, The Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature from inception to November 14, 2018. All English-language qualitative and quantitative articles investigating or reporting the identification, causes, and outcomes of time delays within "high-income" countries (annual gross domestic product per person >$15,000) were included. Data were extracted independently by the investigators. Given the clinical crossover, both conditions were investigated together. A study protocol was designed and registered at the International Prospective Register of Systematic Reviews.
RESULTS
A total of 4780 articles were screened, of which 32 articles, involving 71,310 patients and 1388 health care professionals, were included. Twenty-three articles focused predominantly on DFU. Considerable heterogeneity was noted, and only 12 articles were deemed of high quality. Only four articles defined a delay, but this was not consistent between studies. Median times from symptom onset to specialist health care assessment ranged from 15 to 126 days, with subsequent median times from assessment to treatment ranging from 1 to 91 days. A number of patient and health care factors were consistently reported as potentially causative, including poor symptom recognition by the patient, inaccurate health care assessment, and difficulties in accessing specialist services. Twenty articles reported outcomes of delays, namely, rates of major amputation, ulcer healing, and all-cause mortality. Although results were heterogeneous, they allude to delays being associated with detrimental outcomes for patients.
CONCLUSIONS
Time delays exist in all aspects of the management pathway, which are in some cases considerable in length. The causes of these are complex but reflect poor patient health-seeking behaviors, inaccurate health care assessment, and barriers to referral and treatment within the care pathway. The adoption of standardized limits for referral and treatment times, exploration of missed opportunities for diagnosis, and investigation of novel strategies for providing specialist care are required to help reduce delays.
Topics: Chronic Disease; Delayed Diagnosis; Diabetic Foot; Humans; Ischemia; Lower Extremity; Time-to-Treatment; Treatment Outcome
PubMed: 31676182
DOI: 10.1016/j.jvs.2019.08.229 -
Journal of Vascular Surgery Oct 2022In 2019, the Global Vascular Guidelines on chronic limb-threatening ischemia (CLTI) introduced the concept of limb-based patency (LBP) defined as maintained patency of a...
OBJECTIVE
In 2019, the Global Vascular Guidelines on chronic limb-threatening ischemia (CLTI) introduced the concept of limb-based patency (LBP) defined as maintained patency of a target artery pathway after intervention. The purpose of this study was to investigate the relationship between LBP and major adverse limb events (MALE) after infrainguinal revascularization for CLTI.
METHODS
Consecutive patients undergoing revascularization for CLTI between 2016 and 2019 at a single tertiary institution with a dedicated limb preservation team were included. Subjects with aortoiliac disease, prior infrainguinal stents, or existing bypass grafts were excluded. Demographics, Global Limb Anatomic Staging System scores, Wound, Ischemia, foot Infection (WIfI) stages, revascularization details, and limb-specific outcomes were reviewed. LBP was defined by the absence of reintervention, occlusion, critical stenosis (>70%), or hemodynamic compromise with ongoing symptoms of CLTI. MALE included thrombectomy or thrombolysis, new bypass, open surgical graft revision and/or major amputation.
RESULTS
We analyzed 184 unique limbs in 163 patients. This cohort was composed of 66.9% male patients with a mean age of 72 years. Baseline characteristics included diabetes (66%), tissue loss (91%), and advanced WIfI stages (30% stage 3, 51% stage 4). Global Limb Anatomic Staging System stage 3 anatomic patterns were common (n = 119 [65%]). Sixty limbs were treated with open bypass (65% involving tibial targets) and 124 underwent endovascular intervention (70% including infrapopliteal targets). The 12-month freedom from MALE and loss of LBP were 74.0% ± 3.7% and 48.6% ± 4.2%, respectively. Diabetes (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.13-5.83; P = .025) and loss of LBP (HR, 4.12; 95% CI, 1.96-8.64; P < .001) were independent predictors of MALE in a Cox proportional hazard model. Loss of LBP was the sole independent predictor of major limb amputation after revascularization (HR, 4.97; 95% CI, 1.89-13.09; P = .001). Loss of LBP impacted both intermediate-risk limbs (HR, 2.85; 95% CI, 1.02-7.97; P = .047 in WIfI stages 1-3) and high-risk limbs (HR, 3.99; 95% CI, 1.32-12.11; P = .014 in WIfI stage 4). However, the loss of LBP had the greatest impact on patients presenting with WIfI stage 4 disease (31% vs 8% major limb amputation at 12 months in limbs without vs with maintained LBP).
CONCLUSIONS
The anatomic durability of revascularization, as measured by LBP, is a key determinant of treatment outcomes in CLTI regardless of the initial mode of intervention undertaken. Loss of LBP is most detrimental in patients presenting with advanced limb threat (WIfI stage 4).
Topics: Aged; Amputation, Surgical; Chronic Limb-Threatening Ischemia; Endovascular Procedures; Female; Humans; Ischemia; Limb Salvage; Lower Extremity; Male; Peripheral Arterial Disease; Retrospective Studies; Risk Factors; Treatment Outcome
PubMed: 35697305
DOI: 10.1016/j.jvs.2022.04.042 -
PloS One 2022There is limited qualitative research on the experience of patients undergoing lower limb amputation due to chronic limb threatening ischemia (CLTI) and their...
PURPOSE
There is limited qualitative research on the experience of patients undergoing lower limb amputation due to chronic limb threatening ischemia (CLTI) and their participation in amputation-level decisions. This study was performed to understand patient lived experiences related to amputation and patient involvement in shared decision making.
MATERIALS AND METHODS
Phenomenological interviews were conducted with Veterans 6-12 months post transtibial or transmetatarsal amputation due to CLTI. Interviews were read and summarized by two analysts who discussed the contents of each interview and relationships between interviews to identify emergent, cross-cutting elements of patient experience.
RESULTS
Twelve patients were interviewed between March and August 2019. Three cross cutting elements of patient lived experience and participation in shared decision making were identified: 1) Lacking a sense of decision making; 2) Actively working towards recovery as response to a perceived loss of independence; and 3) Experiencing amputation as a Veteran.
CONCLUSIONS
Patients did not report a high level of involvement in shared decision making about their amputation or amputation level. Understanding patient experiences and priorities is crucial to supporting shared decision making for Veterans with amputation due to CLTI.
Topics: Amputation, Surgical; Chronic Limb-Threatening Ischemia; Foot; Humans; Ischemia; Limb Salvage; Peripheral Arterial Disease; Risk Factors; Treatment Outcome; Veterans; Veterans Health
PubMed: 35303030
DOI: 10.1371/journal.pone.0265620 -
Journal of Cardiology Jan 2022The current study aimed to reveal clinical features and prognosis of asymptomatic contralateral limbs in patients undergoing revascularization for chronic...
BACKGROUND
The current study aimed to reveal clinical features and prognosis of asymptomatic contralateral limbs in patients undergoing revascularization for chronic limb-threatening ischemia (CLTI).
METHODS
We analyzed a database of 520 CLTI patients registered in a prospective, multicenter registry in Japan. Severe ischemia in asymptomatic contralateral limbs was determined as the Wound, Ischemia, and foot Infection (WIfI) classification system Ischemia (I) grade 2/3.
RESULTS
The prevalence of diabetes mellitus and dialysis-dependent renal failure was 74.2% and 53.5%, respectively. Asymptomatic limbs accounted for 65.0% [95% confidence interval (CI), 60.9-69.1%] of the overall population, and 55.0% (95% CI, 49.6-60.4%) of the asymptomatic contralateral limbs had WIfI I-2/3. The multivariate analysis identified age ≥65 years, dialysis-dependent renal failure, WIfI I-3 in the index limb, and loss of pressure sensation in the contralateral limb as independent risk factors for WIfI I-2/3 in asymptomatic contralateral limbs (all p < 0.05). The 3-year cumulative incidence rate of major adverse limb events (MALE) in asymptomatic contralateral limbs was 19.3% (95% CI, 15.1-23.7%), whereas that of all-cause mortality was 46.9% (95% CI, 41.0-52.5%). The corresponding rate including a composite of mortality and MALE was 58.8% (95% CI, 52.9-64.6%). In asymptomatic contralateral limbs, the adjusted hazard ratio of WIfI I-2/3 versus I-0/1 was 1.53 (95% CI, 1.11-2.10) for a composite of mortality and MALE, 1.96 (95% CI, 1.14-3.36) for MALE, and 1.37 (95% CI, 0.95-1.96) for mortality (p = 0.009, 0.015, and 0.091, respectively).
CONCLUSIONS
Two-thirds of CLTI patients had an asymptomatic contralateral limb, and approximately half of the asymptomatic contralateral limbs were exposed to severe ischemia. Older age, dialysis-dependent renal failure, WIfI I-3 in the index limb, and loss of pressure sensation in the contralateral limb were independently associated with severe ischemia in asymptomatic contralateral limbs. In addition to mortality, MALE commonly occurred in asymptomatic contralateral limbs, especially with WIfI I-2/3.
Topics: Aged; Amputation, Surgical; Chronic Disease; Chronic Limb-Threatening Ischemia; Humans; Ischemia; Limb Salvage; Peripheral Arterial Disease; Predictive Value of Tests; Prospective Studies; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 34470712
DOI: 10.1016/j.jjcc.2021.08.021 -
Journal of Vascular Surgery Mar 2023Despite societal guidelines that peripheral vascular intervention (PVI) should not be the first-line therapy for intermittent claudication, a significant number of...
OBJECTIVE
Despite societal guidelines that peripheral vascular intervention (PVI) should not be the first-line therapy for intermittent claudication, a significant number of patients will undergo PVI for claudication within 6 months of diagnosis. The aim of the present study was to investigate the association of early PVI for claudication with subsequent interventions.
METHODS
We evaluated 100% of Medicare fee-for-service claims to identify all beneficiaries with a new diagnosis of claudication from January 1, 2015 to December 31, 2017. The primary outcome was late intervention, defined as any femoropopliteal PVI performed >6 months after the claudication diagnosis (through June 30, 2021). Kaplan-Meier curves were used to compare the cumulative incidence of late PVI for claudication patients with early (≤6 months) PVI vs those without early PVI. A hierarchical Cox proportional hazards model was used to evaluate the patient- and physician-level characteristics associated with late PVIs.
RESULTS
A total of 187,442 patients had a new diagnosis of claudication during the study period, of whom 6069 (3.2%) had undergone early PVI. After a median follow-up of 4.39 years (interquartile range, 3.62-5.17 years), 22.5% of the early PVI patients had undergone late PVI vs 3.6% of those without early PVI (P < .001). Patients treated by high use physicians of early PVI (≥2 standard deviations; physician outliers) were more likely to have received late PVI than were patients treated by standard use physician of early PVI (9.8% vs 3.9%; P < .001). Patients who had undergone early PVI (16.4% vs 7.8%) and patients treated by outlier physicians (9.7% vs 8.0%) were more likely to have developed CLTI (P < .001 for both). After adjustment, the patient factors associated with late PVI included receipt of early PVI (adjusted hazard ratio [aHR], 6.89; 95% confidence interval [CI], 6.42-7.40) and Black race (vs White; aHR, 1.19; 95% CI, 1.10-1.30). The only physician factor associated with late PVI was a majority of practice in an ambulatory surgery center or office-based laboratory, with an increasing proportion of ambulatory surgery center or office-based laboratory services associated with significantly increased rates of late PVI (quartile 4 vs quartile 1; aHR, 1.57; 95% CI, 1.41-1.75).
CONCLUSIONS
Early PVI after the diagnosis of claudication was associated with higher late PVI rates compared with early nonoperative management. High use physicians of early PVI for claudication performed more late PVIs than did their peers, especially those primarily delivering care in high reimbursement settings. The appropriateness of early PVI for claudication needs critical evaluation, as do the incentives surrounding the delivery of these interventions in ambulatory intervention suites.
Topics: Humans; Aged; United States; Intermittent Claudication; Chronic Limb-Threatening Ischemia; Peripheral Arterial Disease; Endovascular Procedures; Risk Factors; Treatment Outcome; Medicare; Limb Salvage; Retrospective Studies; Ischemia
PubMed: 37276171
DOI: 10.1016/j.jvs.2022.10.025 -
Cardiovascular Therapeutics 2023The response to ischemia in peripheral artery disease (PAD) depends on compensatory neovascularization and coordination of tissue regeneration. Identifying novel...
The response to ischemia in peripheral artery disease (PAD) depends on compensatory neovascularization and coordination of tissue regeneration. Identifying novel mechanisms regulating these processes is critical to the development of nonsurgical treatments for PAD. E-selectin is an adhesion molecule that mediates cell recruitment during neovascularization. Therapeutic priming of ischemic limb tissues with intramuscular E-selectin gene therapy promotes angiogenesis and reduces tissue loss in a murine hindlimb gangrene model. In this study, we evaluated the effects of E-selectin gene therapy on skeletal muscle recovery, specifically focusing on exercise performance and myofiber regeneration. C57BL/6J mice were treated with intramuscular E-selectin/adeno-associated virus serotype 2/2 gene therapy (E-sel/AAV) or LacZ/AAV2/2 (LacZ/AAV) as control and then subjected to femoral artery coagulation. Recovery of hindlimb perfusion was assessed by laser Doppler perfusion imaging and muscle function by treadmill exhaustion and grip strength testing. After three postoperative weeks, hindlimb muscle was harvested for immunofluorescence analysis. At all postoperative time points, mice treated with E-sel/AAV had improved hindlimb perfusion and exercise capacity. E-sel/AAV gene therapy also increased the coexpression of MyoD and Ki-67 in skeletal muscle progenitors and the proportion of Myh7 myofibers. Altogether, our findings demonstrate that in addition to improving reperfusion, intramuscular E-sel/AAV gene therapy enhances the regeneration of ischemic skeletal muscle with a corresponding benefit on exercise performance. These results suggest a potential role for E-sel/AAV gene therapy as a nonsurgical adjunct in patients with life-limiting PAD.
Topics: Mice; Animals; Neovascularization, Physiologic; E-Selectin; Mice, Inbred C57BL; Muscle, Skeletal; Ischemia; Genetic Therapy; Peripheral Arterial Disease; Hindlimb; Muscle Development; Disease Models, Animal
PubMed: 37251271
DOI: 10.1155/2023/6679390