Filgrastim, fibrinolysis, and neovascularization

Objective: Segmental recanalization of chronically occluded arteries was observed in patients with chronic limb-threatening ischemia (CLTI) treated with Filgrastim, a granulocyte colony stimulating factor, every 72 hours for up to a month, and an infra-geniculate programmed compression pump (PCP) for 3 hours daily. Molecular evidence for fibrinolysis and neovascularization was sought.
Methods: CLTI patients were treated with PCP alone (N=19), or with Filgrastim and PCP (N=8 and N=6, at 2 institutions). ELISA was used to measure the plasma concentration of Plasmin and of Fibrin Degradation Products (FDP), and the serum concentration of proteins associated with neovascularization. In the PCP alone group blood was sampled on day 1 (baseline) and after 30 days of daily PCP. In the Filgrastim and PCP group blood was drawn on day 1, and one day after the 5th and the 10th Filgrastim doses. Each blood draw occurred before and after 2 hours of supervised PCP.
Results: Significant (p&lt..., Population: CLTI patients who were not candidates for, or had failed, previous invasive revascularization procedures.
Inclusion criteria: Patients complaining of ischemic forefoot rest pain, gangrene, and/or ischemic ulceration were enrolled if the ankle brachial arterial index was <0.45.
Exclusion criteria: Acute limb ischemia, non-salvageable extremity, untreated hypercoagulable disorder, sickle cell disease, myeloproliferative disorder, dialysis, creatinine above 3.5 mg/dl, active cancer, dementia, non-compliance, intolerance of PCP, body mass index over 34, venous stasis ulcer, history of lymphoma or leukemia, uncorrected symptomatic coronary artery disease, severe carotid stenosis, sepsis proximal to the forefoot, allergy to Filgrastim.
Patient groups: Table 2 lists the patient characteristics. Blood assays were performed on 2 patient groups. The first group was treated at a university-affiliated institution (UC, 2012-13) with PCP alone (N=19). The second group (N=14) was t..., Guide

Brackets: “[protein]” mean “concentration of” that protein
T=0: first blood draw on a particular day
T=2HR: blood draw after 2 hours of PCP
Patients 1201-1219: PCP alone at a university-affiliated institution: Table Gaps: two patients stopped PCP before 30 days.
Patients 1401 to 1408: Filgrastim+PCP at a hospital, with all assays done at a university-affiliated institution. Table Gaps: two patients stopped Filgrastim at 5 doses (1404 due to transfer out of state, and 1408 due to resolution of rest pain), and one at 7 doses (1406 due to intolerance of the PCP); one did not store the filgrastim correctly (1401) and had to start over, and one stopped at 5 doses only to resume several months later (1407).
Patients P003-P009: Filgrastim+PCP at a university-affiliated institution:  Table Gap: P009 had only one blood draw on last day (T=0): did not wear PCP on that day.
, The human data obtained from the University affiliated hospitals were obtained and published with each patient's consent., # Filgrastim, fibrinolysis, and neovascularization

Dataset DOI: [10.5061/dryad.b2rbnzsgw](10.5061/dryad.b2rbnzsgw)

## Description of the data and file structure

The key hematologic and ELISA data were obtained in patients treated with Filgrastim and the ArtAssist Device together, and were derived from 2 independent university-affiliated institutions from patients with Chronic Limb Threatening Ischemia (CLTI) recruited from the Vascular Surgery practices at each institution. The control group of hematologic and ELISA data was obtained from patients treated with the ArtAssist Device alone. The goal was to measure hematologic (CD34, VEGFR2) and ELISA evidence supporting clinical evidence of neovascularization (VEGF, HGF, MMP9, PDGF...) in patient serum and of fibrinolysis (plasmin, Fibrin Degradation Products) in patient plasma and serum. Also, in the control group, the goal was to measure evidence of endothelial cell activation by the ArtAssist device, including MCP-1 serum level (ELIS...

### 研究目标
在接受每72小时一次、最长持续1个月的非格司亭（Filgrastim，一种粒细胞集落刺激因子）联合每日3小时膝下程序化加压泵（infra-geniculate programmed compression pump, PCP）治疗的慢性肢体威胁性缺血（chronic limb-threatening ischemia, CLTI）患者中，观察到慢性闭塞动脉的节段性再通。本研究旨在探寻纤溶与新生血管形成的分子学证据。

### 研究方法
本研究纳入的CLTI患者分别接受单纯PCP治疗（N=19），或联合非格司亭与PCP治疗（来自2家研究机构的N=8与N=6）。采用酶联免疫吸附试验（ELISA）检测血浆纤溶酶（Plasmin）与纤维蛋白降解产物（Fibrin Degradation Products, FDP）的浓度，以及血清中与新生血管形成相关蛋白的浓度。单纯PCP治疗组分别于第1天（基线）及每日PCP治疗30天后采集血液样本。非格司亭联合PCP治疗组则于第1天、第5次和第10次非格司亭给药后1天采集血液样本。所有血液采集均在监督下的PCP治疗2小时前后进行。

### 研究结果
显著（p<……）（原文截断）

### 研究人群
纳入既往有创血管重建术治疗无效或无治疗指征的CLTI患者。

### 纳入标准
符合以下条件的缺血性前足静息痛、坏疽和/或缺血性溃疡患者纳入本研究：踝肱指数<0.45。

### 排除标准
急性肢体缺血、不可挽救的肢体、未治疗的高凝状态疾病、镰状细胞病、骨髓增殖性疾病、透析治疗、肌酐>3.5mg/dl、活动性恶性肿瘤、痴呆、治疗依从性差、无法耐受PCP、体重指数>34、静脉性溃疡、淋巴瘤或白血病病史、未矫正的症状性冠状动脉疾病、重度颈动脉狭窄、前足近端败血症、对非格司亭过敏。

### 患者分组
表2列出了患者的基线特征。本研究对2组患者进行了血液检测。第一组于大学附属医疗机构（UC，2012-2013年）接受单纯PCP治疗（N=19）。第二组（N=14）为……（原文截断）。

### 补充说明
1. 括号说明：`[protein]`表示「该蛋白的浓度」
2. T=0：某一日的首次血液采集
3. T=2HR：PCP治疗2小时后的血液采集
4. 患者1201-1219：于大学附属医疗机构接受单纯PCP治疗：数据缺失：2名患者在30天治疗前停止了PCP治疗。
5. 患者1401至1408：于某医院接受非格司亭+PCP治疗，所有检测均于大学附属医疗机构完成。数据缺失：2名患者在完成5次给药后停止非格司亭治疗（1404号患者因转至外州，1408号患者因静息痛缓解），1名患者在完成7次给药后停止治疗（1406号患者因无法耐受PCP）；1名患者未正确储存非格司亭（1401号），需重新开始给药，1名患者在完成5次给药后停止治疗，数月后恢复给药（1407号）。
6. 患者P003-P009：于大学附属医疗机构接受非格司亭+PCP治疗：数据缺失：P009仅在治疗最后一日完成1次血液采集（T=0），当日未佩戴PCP。

本研究从大学附属医院获取的人类数据均已获得每位患者的知情同意后采集并发表。

# 非格司亭、纤溶与新生血管形成
数据集DOI：[10.5061/dryad.b2rbnzsgw](10.5061/dryad.b2rbnzsgw)

## 数据与文件结构说明
本研究的核心血液学与ELISA数据来自接受非格司亭与ArtAssist装置联合治疗的CLTI患者，数据来源于2家独立的大学附属医疗机构，招募自各机构的血管外科门诊患者。血液学与ELISA数据的对照组来自仅接受ArtAssist装置治疗的患者。本研究旨在检测患者血清中与新生血管形成相关的血液学（CD34、VEGFR2）及ELISA标志物（VEGF、HGF、MMP9、PDGF……）证据，以及患者血浆与血清中纤溶相关标志物（纤溶酶、FDP）的临床证据。在对照组中，本研究同时旨在检测ArtAssist装置诱导内皮细胞活化的证据，包括血清MCP-1水平（ELISA……）