Prognostic Implications of Initial Focal Contrast Enhancement in Acute Type B Intramural Hematoma.

BACKGROUND: The prognostic implication of initial focal contrast enhancement (FCE), including focal intimal disruption (FID) and intramural blood pool (IBP), in acute type B intramural hematoma (IMH) remain unclear. OBJECTIVES: The purpose of this study was to compare the prognostic implications in IMH with or without FCE. METHODS: A total of 574 patients were enrolled. FID was defined as an intimal disruption with contrast-filled out-pouching from the aorta lumen with a communicating orifice of >3 mm, and IBP was defined as a localized contrast medium-filled pool inside the IMH. RESULTS: A total of 207 (36.1%) patients with initial FCE, including 132 (63.8%) FIDs and 75 (36.2%) IBPs, were identified. Patients with FCE accompanying IMH were more likely to have hypertension (P = 0.001), pleural effusion (P = 0.006), fewer aortic segments involved (P < 0.001), more adverse aortic events (AAEs) (P < 0.001), and fewer freedom from intervention (P = 0.002). Pleural effusion (HR: 1.79; 95% CI: 1.25-2.55; P = 0.001) and FCE (HR: 1.51; 95% CI: 1.12-2.02; P = 0.006) were identified to be the independent risk factors of AAEs. In the subgroup analysis, IMH with initial FID were more likely to progress than those with initial IBP (P < 0.001). FIDs located at the proximal descending aorta (HR: 2.95; 95% CI: 1.65-5.29; P < 0.001) were associated with AAEs. CONCLUSIONS: Patients with FCE accompanying IMH were more likely to progress, especially in those initial FID localized at the proximal descending aorta. (Nature course and predictors of progression of intramural hematoma: A retrospective, multicenter study; ChiCTR2300073829).

Exploration of SERPINA family functions and prognostic value in breast cancer based on transcriptome and in vitro analysis.

Breast cancer poses a significant risk to women worldwide, yet specific role of SERPINA gene family in breast cancer remains unclarified. Data were collected from online databases. SERPINA family gene expression was presented, and prognosis value was evaluated. Multi-omics methods were employed to explore the SERPINA-related biological processes, followed by comprehensive analyses of their roles in breast cancer. Single-cell data were analyzed to characterize the SERPINA family gene expression in different cell clusters. We selected SERPINA5 as the target gene. Via pan-cancer analysis, SERPINA5 was also investigated in various cancers. The experimental validation was conducted in MDA-MB-231 cell line eventually. SERPINA family showed differential expression in breast cancer, which were mainly expressed in myeloid cells, epithelial cells, and dendritic cells. SERPINA5 expression was upregulated in breast cancer, which was associated with a better prognosis. Immune infiltration illustrated the positive correlativity between SERPINA5 intensity and eosinophilic recruitment. Pan-cancer analysis indicated the function of SERPINA5 as a potential biomarker in other cancers. Finally, experimental validation demonstrated that SERPINA5 contributes to lower invasion and metastatic potential of breast cancer cells. With bioinformatics analysis, the significant role SERPINA family genes functioned in breast cancer was comprehensively explored, with SERPINA5 emerging as a key gene in suppressing breast cancer progression.

Risk factors for at-risk foot and peripheral artery disease among the population with diabetes: A multicommunity-based cross-sectional study.

AIMS: This study aimed to investigate the prevalence, characteristics, and influence factors of the at-risk foot with diabetes mellitus (DM). METHODS: This study included 3030 DM patients from the at-risk foot screening program of Shanghai in China between March 21 and April 30 in 2021. Data were collected from the questionnaire survey, physical examination, and fasting blood sample. RESULTS: The prevalence of at-risk foot was 27.8% among DM patients. After adjusted, the risk of higher at-risk grade increased with age and urinary albumin creatinine ratio (OR = 1.04, 95%CI = 1.02-1.06; OR = 1.001, 95%CI = 1.000-1.002, respectively), whereas decreased with estimated glomerular filtration rate (eGFR) (OR = 0.991, 95%CI = 0.984-0.998). The incidence of peripheral artery disease (PAD) was 11.1% in all people with DM, and age, pulse rate, and low-density lipoprotein were independent risk factors for PAD. In contrast, high-density lipoprotein, eGFR, and lymphocyte-to-monocyte ratio were independent protective factors for PAD. Glycated hemoglobin HbA1c was not an independent risk factor for increased risk grade or more severe PAD. CONCLUSIONS: The at-risk foot accounted for a high percentage among DM patients. Advanced age and renal dysfunction are independent risk factors for the at-risk foot. Glycemic control does not reduce the risk grade of at-risk foot and the incidence of PAD.

Evaluation of the lower extremity blood supply in no-option critical limb ischemia patients with stem cell transplantation by time maximum intensity projection CT perfusion: A single-centre prospective study.

OBJECTIVES: Cell therapy has had satisfactory safety and efficacy outcomes for no-option critical limb ischaemia (NO-CLI) patients. In the current study, we aimed to compare the image quality of ischaemic lower limb blood vessels shown on volumetric CT-based time maximum intensity projection CT perfusion (t-MIP CTP) versus single-phase CTA (sCTA). We also tried to quantify the blood flow of the ischaemic lower extremity based on the t-MIP technique, not only to precisely show the dynamic change in blood flow from before to after cell therapy but also to detect any relationship between this change and patient prognosis. METHODS: A total of 31 patients with thromboangiitis obliterans (TAO)-induced NO-CLI who had been referred from the department of vascular surgery to undergo autologous stem cell transplantation into a single limb from January 2020 to March 2021 were prospectively enrolled in this study. Preoperative sCTA or t-MIP CTP and postoperative 1-month t-MIP CTP were performed in all patients. Clinical outcomes, including the 1-month ankle-brachial index (ABI) and 3-month CLI status, were also analysed. Image quality, including objective scores (attenuation, signal-to-noise ratio [SNR] and contrast-to-noise ratio [CNR]), subjective scores and collateral scores, was compared between preoperative sCTA and t-MIP CTP. Vascular volume was calculated as the total volume (mL) of lower limb arteries within the scanning range. All images and calculations were performed by 2 separate radiologists. Receiver operating characteristic curves were drawn to reveal the sensitivity and specificity of vascular volume and ABI in predicting prognosis. RESULTS: Both sCTA and t-MIP CTP images exhibited good quality for diagnosis. t-MIP CTP images showed significantly higher attenuation, SNR and CNR in all arterial segments (popliteal artery, anterior tibial artery, posterior tibial artery and peroneal artery). In subjective and collateral score evaluations, t-MIP CTP images were also significantly better than sCTA images (both p < .05). At 1 month after transplantation, both vascular volume and ABI showed significant improvement (both p < .01). At 3 months after transplantation, 38.71% of patients (12/31) achieved CLI relief (Rutherford class < 4). Through the receiver operating characteristic (ROC) curve, the 1-month vascular volume increase ratio showed better ability to predict the 3-month prognosis (radiologist 1: AUC, 0.757; sensitivity, 0.750; specificity, 0.840; radiologist 2: AUC, 0.803; sensitivity, 0.500; specificity, 1.000) than the 1-month ABI increase ratio (AUC, 0.607; sensitivity, 0.230; specificity, 0.820) or 1-month ABI (AUC, 0.410; sensitivity, 0.080; specificity, 0.580). CONCLUSION: t-MIP CTP showed significantly higher-quality images of ischaemic limb vascularity than sCTA. t-MIP CTP can reveal the anatomical information of collaterals more accurately, which is of great importance for NO-CLI patients undergoing cell transplantation. The 1-month vascular volume increase ratio can predict the 3-month prognosis more precisely on this basis.

The efficacy and safety of Gore conformable thoracic stent graft and Valiant Captivia thoracic stent graft for acute type B aortic dissection.

BACKGROUND: To evaluate the safety and efficacy of the conformable thoracic aortic endograft (Conformable TAG Thoracic Endoprosthesis [CTAG]; W. L. Gore & Associates, Flagstaff, Ariz) and Valiant Captivia thoracic stent graft (Medtronic Inc., Santa Rosa, CA) for acute type B aortic dissection (TBAD). METHODS: The early and mid-term outcomes were analyzed for 413 patients undergoing TEVAR using conformable TAG thoracic endoprosthesis and Valiant Captivia thoracic stent graft for acute TBAD. 100 propensity-matched pairs of patients were generated, including 100 patients in the CTAG group and 200 patients in the Valiant Captivia group. RESULTS: Operative mortality were 2.33% (3 of 129) in the CTAG group and 1.76% (5 of 284) in the Valiant Captivia group. The median follow-up was 41.67 (26.00-60.67) months. No significant difference in mortality (9 [7.00%] vs. 36 [12.68%], P = 0.95) or re-intervention rate (3 [2.33%] vs. 20 [7.04%], P = 0.29) was observed between two groups. CTAG group have a lower incidence rate of distal stent graft-induced new entry tear than Valiant Captivia group (2.33% vs. 9.86%, P = 0.045). Lower incidence of type Ia endoleak was identified in the CTAG group (2.22%) than the Valiant Captivia group (14.41%) in patients with type III arch (P = 0.039). CONCLUSIONS: Both Valiant Captivia thoracic stent graft and CTAG thoracic endoprosthesis can be safely performed for acute TBAD with low operative mortality, favorable mid-term survival and freedom from reintervention. CTAG thoracic endoprosthesis had fewer dSINE even with larger oversizing and potentially suitable for type III arch with fewer type Ia endoleaks.

Comparison between endovascular aneurysm repair-selected and endovascular aneurysm repair-only strategies for the management of ruptured abdominal aortic aneurysms: An 11-year experience at a Chinese tertiary hospital.

Objectives: The aim of this study was to review our management experience of ruptured abdominal aortic aneurysms (RAAAs) using an endovascular aneurysm repair (EVAR)-only strategy, and discuss the feasibility of this strategy. Materials and methods: A retrospective analysis of clinical data was performed in patients with RAAAs from January 2009 to October 2020. Our strategy toward operative treatment for RAAAs evolved from an EVAR-selected (from January 2009 to April 2014) to an EVAR-only (from May 2014 to October 2020) strategy. Baseline characteristics, thirty-day mortality, perioperative complications, and long-term outcomes of patients were compared between the two periods. Results: A total of 93 patients undergoing emergent RAAA repair were eventually included. The overall operation rate in RAAAs at our centre was 70.5% (93/132). In the EVAR-only period, all 53 patients underwent ruptured endovascular aneurysm repair (rEVAR). However, only 47.5% (19/40) of patients in the EVAR-selected period underwent rEVAR, and the remaining 21 patients underwent emergent open surgery. Thirty-day mortality in the EVAR-only group was 22.6% (12/53) compared with 25.0% (10/40) for the EVAR-selected group (P = 0.79). Systolic blood pressure ≤70 mmHg [adjusted odds ratio (OR) 4.99, 95% confidence interval (CI), 1.13-22.08, P = 0.03] and abdominal compartment syndrome (adjusted OR 3.72, 95% CI, 1.12-12.32, P = 0.03) were identified as independent risk factors responsible for 30-day mortality. After 5 years, 47.5% (95% CI, 32.0-63.0%) of patients in the EVAR-selected group were still alive versus 49.1% (95% CI, 32.3-65.9%) of patients in the EVAR-only group (P = 0.29). Conclusion: The EVAR-only strategy has allowed rEVAR to be used in nearly all the RAAAs with similar mortality comparing with the EVAR-selected strategy. Due to the avoidance of operative modality selection, the EVAR-only strategy was associated with a more simplified algorithm, less influence on haemodynamics, and a shorter operation and recovery time.

Autologous Stem Cells Transplantation for No-Option Angiitis-Induced Critical Limb Ischemia: Recurrence and New Lesion.

Although satisfying outcomes have been demonstrated in terms of autologous stem cell transplantation in the treatment of angiitis-induced critical limb ischemia (AICLI), few studies have systematically reported the recurrence conditions. In the current study, we aimed to investigate recurrence conditions of a relatively large AICLI cohort in our center during a long-term follow-up period. From May 2009 to August 2020, 181 patients with AICLI received peripheral blood mononuclear cells (PBMNCs) or purified CD34+ cells (PCCs) transplantation. The main outcomes included recurrence and new lesions. Patient demographic data, ischemic limb characteristics, interventional characteristics, etc., were identified and analyzed. A logistic multivariable regression was performed to identify the independent risk factors for recurrence by a stepwise selection of variables. One hundred forty-eight patients were enrolled in this study. The mean follow-up period was 62.3 ± 37.4 months (range 12-144 months). The 5- and 10-year recurrence-free rates were 88.5% (95% confidence interval [CI] 3.1%-82.6%) and 71.7% (95% CI 7.6%-58.2%), respectively. The 5- and 10-year new lesion-free rates were 93.2% (95% CI 2.2%-89.0%) and 91.7% (95% CI 2.7%-86.6%), respectively. The finding of multiple limbs involved (OR 1.322 95% CI 1.123-12.549, P = .036) and ischemia relief period ≥5 months (OR 3.367 95% CI 1.112-10.192, P = .032) were demonstrated to be independent risk factors for recurrence in patients with AICLI who underwent cell transplantation. For patients with AICLI who responded to cell transplantation, the durability of this therapy was satisfactory, with 5- and 10-year recurrence-free rates of 88.5% and 71.7%, respectively. Multiple limbs involved at admission and ischemia relief period ≥5 months were demonstrated to be independent risk factors for recurrence after transplantation.

Return to work after cell transplantation in patients with angiitis-induced critical limb ischaemia and factors related: a single-centre retrospective cohort study.

BACKGROUND: Angiitis-induced critical limb ischaemia (AICLI) patients, who are usually young and have a high amputation rate, always lose their ability to return to the labour force. Return to work (RTW) not only indicates patients' physical health, showing that they could undertake the work, but also demonstrates their psychological well-being. While cell transplantation showed satisfactory efficacy in limb salvage, few studies of AICLI patients' RTW after transplantation have been reported. METHODS: From May 2009 to May 2021, AICLI patients who underwent cell transplantation and completed no less than 12 months of follow-up were retrospectively enrolled. The primary endpoint was RTW. Patient demographics and characteristics of the ischaemic limbs were reviewed to analyse independent risk factors for RTW. RESULTS: A total of 171 AICLI patients (170 males) were enrolled with a mean age of 41.9 ± 9.6 years (range: 20-57 years). The 12-month and 24-month RTW cumulative rates were 69.4% (95% confidence interval [CI] 61.6-75.6%) and 70.1% (95% CI 62.3-76.2%), respectively. Age < 40 years (odds ratio [OR] 2.659, 95% CI 1.138-6.719) and preoperative occupation as a mental worker (OR 8.930, 95% CI 2.665-42.847) were identified as independent protective factors for RTW. Perioperative limb infection with ulcer or gangrene (OR 0.250, 95% CI 0.075-0.779) was identified as an independent risk factor. CONCLUSION: AICLI patients who underwent cell transplantation usually had a satisfactory midterm RTW cumulative rate. AICLI patients < 40 years old with preoperative occupation as mental workers were more likely to return to work. Prevention of limb infection during the perioperative period is of great significance to RTW.

The peripheral blood mononuclear cells versus purified CD34+ cells transplantation in patients with angiitis-induced critical limb ischemia trial: 5-year outcomes and return to work analysis-a randomized single-blinded non-inferiority trial.

BACKGROUNDS: Patients with AICLI constitute a considerable proportion of NO-CLI patients and cannot be treated with surgical or endovascular treatment. Although cell therapy has shown satisfactory results in treating AICLI, research comparing the efficacy of treatment with the 2 kinds of cell products is rare. The aim of this study was to report the 5-year outcomes of a randomized single-blinded noninferiority trial (Number: NCT02089828) on peripheral blood mononuclear cells (PBMNCs) and purified CD34+ cells (PCCs) transplantation for treating angiitis-induced critical limb ischemia (AICLI). METHODS: A randomized single-blinded non-inferiority trial (Number: NCT02089828) was performed. Fifty patients were randomized 1:1 to the PBMNCs and PCCs groups. Efficacy outcomes, safety outcomes and patients' work conditions were analyzed. The primary efficacy outcomes included major amputation and total amputation over 60 months. RESULTS: During the 60-month follow-up, 1 patient was lost to follow-up, 1 died, and 2 underwent major amputation. The major amputation-free survival rate (MAFS) was 92.0% (95% confidence interval [CI] 82.0%-100.0%) in the PBMNCs group and 91.7% (95% CI 81.3%-100.0%) in the PCCs group (P = 0.980). Compared with the PCCs group, the PBMNCs group had a significantly higher 5-year new lesion-free survival rate (100.0% vs. 83.3% [95% CI 69.7-99.7%], P = 0.039). All patients lost their ability to work before transplantation, and the 5-year cumulative return to work (RTW) rates were 88.0% in the PBMNCs group and 76.0% in the PCCs group (P = 0.085). CONCLUSION: The long-term follow-up outcomes of this trial not only demonstrated similar efficacy and safety for the 2 types of autoimplants but also showed a satisfactory cumulative RTW rate in AICLI patients who underwent cell transplantation. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02089828. Registered 14 March 2014, https://clinicaltrials.gov/ct2/show/record/NCT02089828 .

Prediction of 2-Year Major Adverse Limb Event-Free Survival After Percutaneous Transluminal Angioplasty and Stenting for Lower Limb Atherosclerosis Obliterans: A Machine Learning-Based Study.

BACKGROUND: The current scoring systems could not predict prognosis after endovascular therapy for peripheral artery disease. Machine learning could make predictions for future events by learning a specific pattern from existing data. This study aimed to demonstrate machine learning could make an accurate prediction for 2-year major adverse limb event-free survival (MFS) after percutaneous transluminal angioplasty (PTA) and stenting for lower limb atherosclerosis obliterans (ASO). METHODS: A lower limb ASO cohort of 392 patients who received PTA and stenting was split to the training set and test set by 4:1 in chronological order. Demographic, medical, and imaging data were used to build machine learning models to predict 2-year MFS. The discrimination and calibration of artificial neural network (ANN) and random forest models were compared with the logistic regression model, using the area under the receiver operating curve (ROCAUC) with DeLong test, and the calibration curve with Hosmer-Lemeshow goodness-of-fit test, respectively. RESULTS: The ANN model (ROCAUC = 0.80, 95% CI: 0.68-0.89) but not the random forest model (ROCAUC = 0.78, 95% CI: 0.66-0.87) significantly outperformed the logistic regression model (ROCAUC = 0.73, 95% CI: 0.60-0.83, P = 0.01 and P = 0.24). The ANN model the logistic regression model demonstrated good calibration performance (P = 0.73 and P = 0.28), while the random forest model showed poor calibration (P < 0.01). The calibration curve of the ANN model was visually the closest to the perfectly calibrated line. CONCLUSION: Machine learning models could accurately predict 2-year MFS after PTA and stenting for lower limb ASO, in which the ANN model had better discrimination and calibration. Machine learning-derived prediction tools might be clinically useful to automatically identify candidates for PTA and stenting.

Long-Term Outcomes of Peripheral Blood Mononuclear Cells in the Treatment of Angiitis-Induced No-Option Critical Limb-Threatening Ischemia.

Background: Peripheral blood mononuclear cells (PBMNCs) showed encouraging short outcomes in the treatment of angiitis-induced no-option critical limb-threatening ischemia (AICLTI) in the pilot study. This study aimed to demonstrate the long-term outcomes of this treatment. Methods: From May 2014 to December 2018, patients diagnosed with AICLTI and treated by autotransplantation of PBMNCs in our center were enrolled and analyzed. The primary endpoint was major amputation-free survival (MAFS), the secondary endpoints included peak pain-free walking time (PPFWT), Wong-Baker FACES pain rating scale score (WFPRSS), labor recovery, ankle-brachial index (ABI), transcutaneous partial oxygen pressure (TcpO2), and SF-36v2 scores. Results: A total of 58 patients were enrolled. During a minimal follow-up of 36 months, the MAFS was 93.1% and the labor competence restored rate was 62.1%. The WFPRSS was decreased from 8.7 ± 1.6 to 1.6 ± 3.2, and PPFWT was significantly improved from 2.9 ± 4.2 min to 16.6 ± 6.9 min. The quality of life was also significantly improved at each follow-up point. Perfusion evaluating parameters, such as ABI and TcPO2, were also significantly improved. No critical adverse event was observed during the treatment and follow-up period. Conclusions: The treatment of AICLTI by autotransplantation of PBMNCs demonstrated encouraging long-term results. It could not only restore labor competence, improve the quality of life, but also significantly reduce the major amputation rate.

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.

Outcomes of endovascular stent graft repair for penetrating aortic ulcers with or without intramural hematoma.

OBJECTIVE: We investigated the outcomes of endovascular repair for penetrating aortic ulcers (PAUs) with and without intramural hematoma (IMH). METHODS: Patients with PAUs who had undergone thoracic endovascular aortic repair (TEVAR) or endovascular abdominal aortic repair (EVAR) at our center were enrolled. Patient demographics, presenting symptoms, and anatomic characteristics were collected and analyzed to investigate the TEVAR/EVAR indications, perioperative complications, and mortality. RESULTS: We identified 138 patients with PAU. Of the 138 patients, 58 (42.0%) had also had IMH. Compared with the patients without IMH, the patients with IMH had had significantly greater emergency admission rates (P < .01), a larger aortic diameter (P = .03), and a greater incidence of stent-induced new entry development (P = .02). No significant differences were found in mortality or freedom from reintervention between patients with PAUs with and without IMH during follow-up. However, the cumulative survival rates calculated using Kaplan-Meier analysis for patients who had undergone TEVAR/EVAR during their first hospitalization were significantly greater than those who had undergone delayed TEVAR/EVAR during follow-up. CONCLUSIONS: TEVAR/EVAR was safe and effective, with encouraging outcomes for patients with PAUs with or without IMH, and can be used more aggressively for symptomatic patients. The presence of PAUs with IMH did not seem to adversely affect long-term mortality. However, but stent-induced new entry was more likely to develop.

Autologous peripheral blood-derived stem cells transplantation for treatment of no-option angiitis-induced critical limb ischemia: 10-year management experience.

BACKGROUND: Previous studies have demonstrated that no-option angiitis-induced critical limb ischemia (NO-AICLI) could be significantly improved by transplantation of peripheral blood-derived stem cells (PBDSCs). Additionally, a randomized controlled trial (RCT) recently conducted by us suggested that peripheral blood-derived purified CD34+ cells (PCCs) were not inferior to non-purified peripheral blood mononuclear cells (PBMNCs) at limb salvage in treatment of NO-AICLI. However, most of these clinical trials whether RCT or single-arm studies were characterized with a small sample size and absence of long-term outcomes. METHODS: To analyze long-term clinical outcomes of PBDSCs transplantation for NO-AICLI, we reviewed clinical data of patients with NO-AICLI receiving PBDSCs transplantation at our center during the past decade. Meanwhile, we first compared the long-term safety and efficacy of intramuscular transplantation of PCCs versus PBMNCs in a sizable number of patients with NO-AICLI. RESULTS: From May 2009 to December 2019, a total of 160 patients with NO-AICLI patients were treated by PBDSCs transplantation (82 with PCCs, 78 with PBMNCs) at our center. Baseline characteristics between two groups were similar. Up to June 2020, the mean follow-up period was 46.6 ± 35.3 months. No critical adverse events were observed in either group. There was one death during the follow-up period. A total of eight major amputations occurred. The cumulative major amputation-free survival (MAFS) rate at 5 years after PBDSCs transplantation was 94.4%, without difference between two groups (P = .855). Wound healing, rest pain, pain-free walking time, ankle-brachial index, transcutaneous oxygen pressure, and quality of life (QoL) also significantly improved after PBDSCs transplantation. CONCLUSIONS: Autologous PBDSCs intramuscular transplantation could significantly decrease the major amputation rates and improve the QoL in patients with NO-AICLI. Long-term observation of a large sample of patients confirmed that the clinical benefits of PBDSCs transplantation were durable, without difference between the PCCs and PBMNCs groups.

Multiple Overlapping Stent Implantation Combined with Coil Embolization for a Suprarenal Aortic Pseudoaneurysm with Impending Rupture in a Patient with Behçet's Disease.

Behçet's disease is an autoimmune vasculitis, which mainly manifests as aneurysm when arteries are involved. Treatments including graft interposition or stent-graft implantation are best performed after active inflammation subsides, otherwise there will be complications such as anastomotic pseudoaneurysms and graft occlusion. We report the treatment of a suprarenal abdominal aortic pseudoaneurysm in a patient with Behçet's disease via multiple overlapping stent implantation combined with coil embolization which was performed in a subacute fashion because of impending rupture of the pseudoaneurysm. She was maintained on long-term immunosuppressive therapy and remained symptom free at 2-year follow-up.

Predictors of responders to mononuclear stem cell-based therapeutic angiogenesis for no-option critical limb ischemia.

BACKGROUND: Although the mononuclear cell (MNC) transplantation could theoretically induce therapeutic angiogenesis in the patients with no-option critical limb ischemia (NO-CLI), the clinical responses to this approach are inconsistent among different clinical trials. The purpose of this study was to identify the prognostic factors of responders and develop a predictive nomogram to guide patient selection. METHODS: We retrospectively reviewed a consecutive NO-CLI cohort who received peripheral blood-derived transplantation in our center. The patients who survived and achieved complete remission of CLI at 6 months post-transplantation were defined as responders. Logistic regression models were used to screen and identify the prognostic factors based on which predictive nomogram was developed. A receiver operating characteristic (ROC) curve and a calibration curve were drawn to determine the discrimination level and predictive accuracy. RESULTS: The study ultimately enrolled 103 patients, including 58 responders and 45 non-responders. Based on the multivariate regression analysis, age ≥ 50 years (odds ratio [OR] 0.201, P = 0.004), blood fibrinogen > 4 g/L (OR 0.176, P = 0.003), arterial occlusion above the knee/elbow (OR 0.232, P = 0.010), the transcutaneous pressure of oxygen (TcPO2) (OR 1.062, P = 0.006), and the Log total transplanted CD34+ cell count (OR 3.506, P = 0.046) were identified as independent prognostic factors of the responders in the nomogram. An area under the ROC curve of 0.851 indicated good discrimination, and the calibration curve of the predicted probability showed optimal agreement with that of the observed probability. CONCLUSIONS: Age, blood fibrinogen, arterial occlusion level, TcPO2, and the total transplanted CD34+ cell count were independent prognostic factors of the responders. A nomogram with high discrimination and accuracy was developed to provide individualized predictions. TRAIL REGISTRATION: ChiCTR, ChiCTR1800019401 . Registered 9 November 2018-Retrospectively registered.

Purified CD34+ cells versus peripheral blood mononuclear cells in the treatment of angiitis-induced no-option critical limb ischaemia: 12-Month results of a prospective randomised single-blinded non-inferiority trial.

BACKGROUND: Peripheral blood mononuclear cells (PBMNCs) and purified CD34+ cells (PCCs) are increasingly being used at treating no-option critical limb ischaemia (NO-CLI). We aimed to compare the efficacies and uncover the advantages associated with each treatment approach. METHODS: A randomised single-blinded non-inferiority trial (Number: NCT 02089828) was performed. NO-CLI patients were 1:1 randomised to the PBMNCs and PCCs groups, and compared in relation to safety and efficacy outcomes. The primary efficacy outcomes included major amputation and total amputation over 12 months. The major amputation-free survival (MAFS) and total amputation-free survival (TAFS) rates were calculated. FINDINGS: Fifty patients (25 per group, 47 with thromboangiitis obliterans and 3 with other angiitis) were enrolled, with a median follow-up period of 24.5 months (interquartile range: 17-34 months). One patient in the PCCs group was lost at 2 months and one major amputation occurred in the PBMNCs group at 3 months post-transplantation. The total amputation rates at 6 months post-transplantation were 28.0% in the PCCs group and 16.0% in the PBMNCs group (p = 0.343), and remained unchanged at 12 months. The groups did not differ regarding the MAFS and TAFS (Breslow-Wilcoxon test: p = 0.3014 and p = 0.3414). The PCCs group had a significantly higher probability of rest pain relief than the PBMNCs group (Breslow-Wilcoxon test: p = 0.0454). INTERPRETATION: PCCs was not inferior to PBMNCs at limb salvage in the treatment of angiitis-induced NO-CLI and appeared to induce earlier ischaemia relief. Each cell type had specific advantages. These outcomes require verification from longer-term trials involving larger numbers of patients. FUND: Training program for outstanding academic leaders of Shanghai health and family planning system (Hundred Talent Program，Grant No. 2018BR40); China National Natural Science Funds (Grant No. 30801122); The excellent core member training programme at Zhongshan Hospital, Fudan University, China (Grant No. 2015ZSYXGG02); and Zhongshan Funds for the Institute of Vascular Surgery, Fudan University, China. CLINICAL TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov (NCT 02089828).

A Five-Year Study of the Efficacy of Purified CD34+ Cell Therapy for Angiitis-Induced No-Option Critical Limb Ischemia.

Angiitis-induced critical limb ischemia (AICLI) patients constitute a remarkable proportion of no-option critical limb ischemia (CLI) patients. Stem cell therapy has become an innovative and promising option for no-option CLI patients. As one of these promising stem cell therapies, purified CD34+ cell transplantation (PuCeT) has shown favorable short-term results. However, the long-term efficacy of PuCeT has yet to be reported. This study evaluates the long-term efficacy of PuCeT in AICLI patients. Twenty-seven AICLI patients were enrolled from May 2009 to December 2011. Granulocyte colony-stimulating factor (G-CSF) and enoxaparin sodium were administered for 5 days. On day 5, CD34+ cell isolation was performed, and cells were transplanted by intramuscular injection. The primary endpoint, major-amputation-free survival rate (MAFS), as well as secondary endpoints, such as peak pain-free walking time (PPFWT) and the Wong-Baker FACES pain rating scale score (WFPRSS), were routinely evaluated during the 5-year follow-up period. The endpoints were as follows: the MAFS was 88.89%; PPFWT increased from 3 ± 3 to 17 ± 6 minutes; WFPRSS decreased from 7 ± 2 to 0.3 ± 1.7; the ulcer healing rate was 85.71%; the recurrence rate was 11.11%; and SF-36v2 scores were significantly improved at 5 years after PuCeT. The rate of labor recovery 5 years after PuCeT was 65.38%, and no severe adverse effect was observed during the treatment. PuCeT demonstrated long-term efficacy and durability as a treatment of AICLI not only in achieving limb salvage but also in recovering the labor competence and improving the quality of life of patients. Stem Cells Translational Medicine 2018;7:583-590.

Therapeutic efficacy of CD34+ cell-involved mononuclear cell therapy for no-option critical limb ischemia: A meta-analysis of randomized controlled clinical trials.

Early-phase clinical trials in patients with critical limb ischemia (CLI) have shown positive results of mononuclear cell therapy. The current meta-analysis investigated whether cluster of differentiation (CD) 34+ mononuclear cell therapy (CD34+MCT) is effective for no-option CLI. Ten randomized controlled clinical studies of CD34+MCT for no-option CLI with 479 patients were identified and analyzed for pooled results. Compared to control groups, the CD34+MCT was associated with lower total amputation (odds ratio (OR): 0.45, p=0.01; 95% confidence interval (CI): 0.24-0.85) and a higher complete ulcer healing rate (OR: 2.80, p=0.008; 95% CI: 1.31-6.02), but showed no advantage in major amputation (OR: 0.58, p=0.11; 95% CI: 0.29-1.14) and all-cause mortality (OR: 0.82, p=0.62; 95% CI: 0.36-1.83) . Studies with a high CD34+ cell dosage showed significant results in major amputation (OR: 0.38, p=0.002; 95% CI: 0.21-0.70), total amputation (OR: 0.31, p=0.0002; 95% CI: 0.17-0.57) and complete ulcer healing (OR: 7.58, p=0.0005; 95% CI: 2.40-23.88), which were not observed in the low-dose studies. However, inclusion of placebo-controlled studies showed no improvement of the CD34+MCT in total amputation (OR: 0.67, p=0.42; 95% CI: 0.25-1.79), major amputation (OR: 1.31, p=0.43; 95% CI: 0.67-2.54) or complete ulcer healing (OR: 1.52, p=0.27; 95% CI: 0.72-3.21), which were extremely significant in non-placebo-controlled studies ( p<0.001). In conclusion, the significant results of CD34+MCT might not support its therapeutic benefit due to high placebo-effect risk and considerable heterogeneity caused by distinct cell doses. More sizable double-blinded, randomized, placebo-controlled trials with higher CD34+ cell dosage are needed in the future.