Abstract
Objective:
To investigate the safety and effectiveness of catheter-based therapy (CBT) compared to conventional catheter-directed thrombosis (CDT) for non-oncological patients with inferior vena cava thrombosis (IVCT), as well to evaluate the differences between CBTs using AngioJet rheolytic thrombectomy (ART) and large lumen catheter aspiration (LLCA).
Methods:
This retrospective single-center study included eligible patients with IVCT treated with CBTs coupled with/without CDT or CDT alone as the first-line treatment between January 3, 2015 and January 28, 2022. The baseline demographics, comorbidities, clinical characteristics, treatment details, course data were all reviewed.
Results:
A total of 106 patients (128 limbs) were included, with 42 cases were treated with ART, 30 with LLCA, and 34 with CDT alone. Technical success rates were 100% (128/128), and 95.5% (84/88) limbs treated with CBT subsequently underwent CDT. The mean duration of CDT time and total infusion agent dosage in patients with CBTs were lower than those who underwent CDT alone (P < .05). Similarities were observed in ART compared to LLCA (P < .05). At the end of CDT, clinical success was achieved in 85.2% (75/88) of limbs treated with CBTs and 77.5% (31/40) of limbs with CDT alone, and 88.5% (46/52) in ART and 80.6% (29/36) in LLCA. The 12-month follow-up showed slightly lower incidences of recurrent thrombosis (7.7% vs 15.2%) and post-thrombotic syndrome (14.1% vs 21.2%), which persisted in patients who underwent ART compared to LLCA (4.3% vs 12.9% and 8.5% vs 22.6%). Patients who underwent CBTs tended to have lower minor complications (5.6% vs 17.6%) but were at higher risk of transient macroscopic hemoglobinuria (58.3% vs 0%) and recoverable acute kidney injury (11.1% vs 2.9%) compared to CDT alone. These findings were similar in ART compared to LLCA (2.4% vs 10.0%, 100% vs 0%, and 16.7% vs 3.3%, respectively). LLCA seemed to have more hemoglobin losses (10.50 ± 9.20 vs 5.57 ± 10. 42 g/L, P < .05).
Conclusion:
CBTs coupled with/without CDT are safe and effective in patients with IVCT, reducing the clot burden in a moderate time, restoring blood flow rapidly, minimizing thrombolytic drug requirement and lowering minor bleeding complication compared to CDT alone. ART and LLCA have comparable outcomes but with different adverse event profiles.
Keywords
Introduction
Acute inferior vena cava thrombosis (IVCT) is an underrecognized but severe condition of venous thromboembolism (VTE), which has wide varieties of clinical manifestations and may present as swelling and discomfort in extremity, or as a series of non-specific or silent symptoms. 1,2 Isolated IVCT is extremely rare and is frequently accompanied by lower extremity deep vein thrombosis (LEDVT). Among these patients, it is estimated that 2.6% to 15% may suffer from IVCT, 2,3 and the prevalence may reach up to 30% in patients with inferior vena cava filter (IVCF), which is a major predisposing factor for the development of IVCT. 4 However, the true incidence may be underestimated due to a lack of standardized screening and the increasing use of IVCF. 2,3 If left untreated, post thrombotic syndrome (PTS) will develop in up to 90% patients with IVCT, disabling venous claudication in 45%, pulmonary embolism (PE) in 30%, and venous ulceration in 15%. 1,2 IVCT also has a mortality rate approximately twice as high as that of deep vein thrombosis (DVT) confined to the lower extremities. 5
Despite the tricky conditions mentioned above, a major clinical challenge still lies in determining the optimal strategies for acute IVCT. 3 Anticoagulation therapy is typically the foundational treatment for IVCT and is essential for mitigating related symptoms and lowering the risk of recurrence. 1,2 However, 20% to 50% of patients with proximal DVT who undergo anticoagulation alone experience unsatisfactory prognosis, 6 particularly when massive clot burden involves the inferior vena cava (IVC). To minimize this untoward sequela, a trend of more aggressive endovascular therapy (ET) has emerged. As previously described, 1,7 a variety of new modalities aimed at mechanical disruption of the clots have emerged, and catheter-based thrombectomy (CBT), including thromboaspiration, microfragmentation, pharmacomechanical thrombectomy, and ultrasound-accelerated catheter-directed thrombolysis (CDT), have become more available. However, most research on CBTs has focused on LEDVT, and relatively little is known about how CBTs compared to conventional CDT, one of the most well-established and commonly used ETs, in critical areas such as safety and competitive device performance in patients with IVCT. 3
We wonder whether the use of CBTs or CDT alone can be considered as an available option for acute IVCT in nononcologic patients, as well as the distinctions of device performance between different CBTs. Hence, the primary objective of this single-center study is to compare the safety and effectiveness of CBTs to conventional CDT in the management of non-oncological patients with IVCT, and the secondary objective is to evaluate the differences in device performance between patients who undergo CBTs using the AngioJet rheolytic thrombectomy (ART) device and those who undergo CBTs using the large lumen catheter (LLC).
Methods
Patients and Study Design
The data collection protocol and informed consent were approved by our Institutional Review Board. We conducted a retrospective cohort study of patients with acute (defined as the duration from related symptom onset to treatment being within 2 weeks) IVCT (with or without associated iliofemoral thrombosis) treated with CBTs or CDT as the first-line treatment at a single academic center between January 3, 2015 and January 28, 2022. Of these patients, 82 (77.4%) had IVCT coupled with unilateral LEDVT, 22 (20.8%) had IVCT and bilateral lower extremity DVT, and 2 (1.9%) had isolated IVCT. The data of baseline demographics, clinical history, hematological and physical examination data, comorbidities and thrombotic risk factors, treatment details, and follow-up findings were retrospectively captured from medical database system and/or the paper records. The exclusion criteria were patients who had confirmed cancer, underwent Straub catheter thrombectomy, underwent CDT using urokinase, were concomitant with heparin-induced thrombocytopenia (HIT) or lack of complete information. A total of 187 patients with ongoing IVCT were recorded, and 81 were subsequently excluded: the confirmed cancer (n = 36), Straub catheter thrombectomy (n = 5), CDT with urokinase (n = 20), concomitant with HIT (n = 8), or lack of complete information (n = 12). Of the remaining 106 eligible patients, 72 underwent CBTs with ART or LLC aspiration (LLCA), and 34 patients underwent CDT alone.
Management Strategies Details
The diagnosis and extent of IVCT were initially verified by CT venography and further confirmed by catheter venography. The management strategies were selected based upon operator preference, economic cost, and device availability. For patients with a potentially life-threatening thrombus in the IVC or above the IVCF, a filter was inserted before the CBTs or CDT procedure and was retrieved after the condition at risk was relieved. Anticoagulant treatment using low molecular weight heparin (LMWH) at a bolus dose of 100 units/kg twice daily was initiated immediately when DVT was identified. CBTs applied in this study were mainly composed of ART or LLCA, coupled with/without CDT or CDT alone, which were performed for mechanical fragmentation, clots aspiration, or thrombus thrombolysis based on a 6F ART catheter (Solent catheter; Boston Scientific, Marlborough, MA, USA), an 8F LLC (Mach1 catheter, Boston Scientific, Marlborough, MA, USA), or 4F multiple-side hole thrombolytic catheter (Uni*Fuse; AngioDynamic; Latham, NY, USA). If under 50% thrombus removal rate was observed at post-CBTs or if patients underwent CDT alone, a dose-reduced thrombolytic therapy of rt-PA was administered, as previously described. 8,9 Balloon angioplasty and/or stent placement were used for lesions that caused over 50% diameter narrowing of the iliocaval vein, robust collateral filling, and/or a mean pressure gradient of more than 2 mmHg. 1,7,8 At the end of LMWH, combined oral warfarin or directed rivaroxaban therapies were used for anticoagulation for at least 6 months. 9 In addition, the use of compression stockings for more than 1 year was recommended.
Definitions of Clinical Outcome and Safety
Technical success of the procedure was defined as the successful completion of CBTs or CDT. The efficacy of CBTs or CDT was evaluated by thrombus scores based on pre- or post-treatment venography imaging. 10 Thrombus removal grades were evaluated as grade III (100% thrombus removal rate), grade II (50%-99%), and grade I (<50%). Grades II and III (i.e., ≥50% thrombus removal rate) were considered as clinical success. Symptom improvement was assessed by measuring the limb circumference difference at 15 cm above the knee and 10 cm below the knee, as well as using a visual analog scale to assess leg pain pre-treatment and at discharge. 8 The outcomes were evaluated at the 12-month follow-up, including recurrent DVT or death, and the resolution of symptoms was evaluated using the Villalta scale 11 via re-examination or telephone.
Safety outcomes included procedure-related complications and thrombolysis/anticoagulant-related complications. The former was related to the manipulation process, and the latter was categorized into major complications, including intracranial bleeding or bleeding-related death, surgery, cessation of therapy, hemoglobin level decrease to 2.0 g/dL, or 2 units blood transfusion, and minor complications, including less severe bleeding manageable with local compression, sheath upsizing, and/or alterations of thrombolytic agent/anticoagulant dose, based on the Society of Interventional Radiology (SIR) reporting standards. 12
Statistical Analysis
Statistical analyses were performed by the SPSS statistical software package (version 23.0; SPSS Inc., Chicago, Illinois, USA). Continuous variables were presented as mean ± standard deviation (SD), while categorical data were shown as proportions. To compare data between patients who underwent CBTs and CDT, or to assess the correlation between pre- and post-treatment variables, the t-test was used. The significance of qualitative variables was tested with a chi-square test or Fisher exact test. Findings with a P < .05 were deemed statistically significant.
Results
Baseline Demographics and Clinical Characteristics
A total of 106 eligible patients [mean age 51.8 years, and 61.3% male (n = 65)] with IV CT were included in this study. Of these, 72 (67.9%) patients underwent CBTs as the first-line treatment, including 42 treated with ART and 30 with LLCA, while the remaining 34 (32.1%) patients underwent CDT alone. The demographics, presentation, lesion characteristics, comorbidities, and risk factors were summarized in Table 1. The onset of IVCF-related symptoms was ≤7 days in 64.2% (68/106) of patients. Regrading thrombus distribution, 94.3% (100/106) occurred in the infrarenal IVC, and 98.1% (104/106) involved iliofemoral vein segments, with 42.5% (45/106) involving the left limb. Of the included patients, 33.0% (35/106) had identified PE. The major comorbidities and risk factors for these patients with IVCT were filter dwelling in 56.6% (60/106) of cases, followed by hypertension (30/106) and a history of major surgery history (25/106). The dwelling time of IVCF mainly focused on ≤30 days (37/60), and the filters used were mainly spindle-shaped (including OptEase filter (27/60) and Aegisy filter (18/60)). The data based on both groups, including age, gender, onset of symptoms at presentation, thrombus segment and limbs involved, dwelling IVCF-related information, comorbidities and risk factors, were all comparable (P > .05).
Demographics, Presentation, Lesion Characteristics, Comorbidities and Risk Factors of Patients With IVCT.a
Abbreviations: IVCT, inferior vena cava thrombosis; CBTs, catheter-based therapies; CDT, catheter-directed thrombosis; SD, standard deviation; DVT, deep vein thrombosis; PE, pulmonary embolism; IVCFs, inferior vena cava filters; VTE, venous thromboembolism; N/A, not applicable.
a Continuous data are presented as the means ± standard deviations; categorical data are given as the counts (percentage).
b Fisher exact test.
Procedure Details, Immediate and Short-Term Follow-Up Outcomes
All 106 patients successfully underwent CBTs or CDT, the technical success rates were both 100%. The incidence of filter-related IVCT was slightly higher in CBTs patients than in CDT patients (61.1% vs 47.1%, P > .05). The filter types included 15 (25.0%) permanent and 45 (75.0%) retrievable filters, while the remaining 46 (43.4%) cases suffered from non-filter related IVCT. Of these patients, 54.7% (58/106) received newly placed filters before undergoing CBTs or CDT. Of which, 100% (46/46) in non-filter related IVCT and 20.0% (12/60) in filter-related IVCT, and all newly placed and 17 previously placed IVCFs were successfully retrieved post-treatment after evaluation. The treatment details and intraoperative procedures are presented in Table 2.
Procedure Induced Characteristics by CBTs or CDT.a
Abbreviations: CBTs, catheter-based therapies; CDT, catheter-directed thrombosis; N/A, not applicable; IVC, inferior vena cava; VTE, venous thromboembolism; PTS, post-thrombotic syndrome; SIR, Society of Interventional Radiology; PE, pulmonary embolism.
a Continuous data are presented as the means ± standard deviations; categorical data are given as the counts (percentages).
b Fisher exact test.
As calculated, a total of 106 patients and 128 limbs [67 (52.3%) in the left limbs, 59 (46.1%) in the right limbs, and 2 (1.56%) in the IVC] were treated with CBTs (88 limbs) or CDT (40 limbs). The thrombus removal grades according to initial venography were all grade I pre-treatments. Following completion of CBTs, 84 (95.5%) limbs evaluated under thrombus removal grade I subsequently received adjunctive CDT with dose-reduced rt-PA. The mean duration of adjunctive CDT time and mean total infusion agent dosage were both lower than those in patients underwent CDT alone (both P < .05). At the end of CDT, clinical success was achieved in 85.2% (75/88) limbs treated with CBTs and 77.5% (31/40) limbs with CDT alone. Comparisons of outcomes by CBTs treatment approach between ART and LLCA were performed and are shown in Table 3. Subgroup analysis showed that the reduced dosage of thrombotic agent and duration of adjunctive CDT continued in patients who underwent ART (P < .05). ART seemed to have a higher rate of thrombus removal grade III (42.3% vs 22.2%, P = .051). The major symptoms, including lower extremity pain and swelling in the affected limbs, were significantly improved in both CBTs (80/88) and CDT (32/40) patients. At completion, iliofemoral or IVC balloon angioplasty (62.5% vs 55.9%, P > .05) and iliofemoral stents (23.6% vs 14.7%, P > .05) were performed.
Comparisons of Outcomes by CBTs Treatment Approach Between ART and LLCA.a
Abbreviations: CBTs, catheter-based therapies; ART, AngioJet rheolytic thrombectomy; LLCA, large lumen catheter aspiration; SD, standard deviation; IVC, inferior vena cava; CDT, catheter-directed thrombosis; VTE, venous thromboembolism; PTS, post-thrombotic syndrome; SIR, Society of Interventional Radiology; PE, pulmonary embolism; N/A, not applicable.
a Continuous data are presented as the means ± standard deviations; categorical data are given as the counts (percentages).
b Fisher exact test.
A total of 89 (83.9%) patients had follow-up information available at the 12-month. Among them, 78 limbs (88.6%) underwent CBTs and 33 limbs (82.5%) underwent CDT alone. The Villalta score was used to evaluate PTS at the 12-month follow-up, and it was found that the frequencies of recurrent VTE and PTS were 7.7% (6/78) versus 15.2% (5/33) and 14.1% (11/78) versus 21.2% (7/33) in patients treated with CBTs and CDT alone, respectively. Among the patients who underwent CBTs, mild PTS (n = 7) and moderate PTS (n = 4) were observed. In contrast, patients who underwent CDT alone presented with mild PTS (n = 3), moderate PTS (n = 3), and severe PTS (n = 1). The subgroup analysis revealed that ART seemed to have a slightly lower recurrence of VTE (4.3% vs 12.9%) and PTS (8.5% vs 22.6%) at the 12-month follow-up.
Safety Outcomes
Except for transient macroscopic hemoglobinuria occurring after the first 24 hours in 42 (58.3%) patients who underwent CBTs, mainly concentrated on patients who underwent ART (42/42), no other procedure-related complications including vessel perforation or damage, bradycardia, arrhythmias, or PE occurred. The incidence of acute kidney injury (AKI) was slightly higher in patients who underwent CBTs compared to patients who underwent CDT alone (11.1% vs 2.9%, P > .05). Among patients who underwent CBTs, AKI was mainly observed in those treated with ART (16.7% vs 3.3%, P > .05), and all recovered after hydration measures during the perioperative period. Minor complications such as bleeding events (SIR A, B category) occurred in 5.6% (4/72) of patients who underwent CBTs compared with 17.6% (6/34) of patients who underwent CDT, including hematoma of the puncture site (n = 5), small hematoma at epistaxis (n = 3), and gingival bleeding (n = 2), ART seemed to have a lower incidence when compared with LLCA (2.4% vs 10.0%, P > .05), and all of the above complications recovered with nominal treatments. No major death event was observed in either group. Notably, 1 (2.9%) patient who underwent CDT suffered from a major complication that required a blood transfusion. In the subgroup analysis between ART and LLCA, LLCA tended to have more hemoglobin losses of 10.50 ± 9.20 g/L when compared to 5.57 ± 10.42 g/L in patients with ART at post-CBTs (P < .05).
Discussion
IVCT, although similar in many aspects to LEDVT, has distinct treatment options. 2,13 These options ranged from conservative anticoagulation with various medicines to open surgical thrombectomy. 2,14 While somewhat effective, open vein thrombectomy proves to be challenging, risky and associated with some adverse events, which has fueled an interest in ETs. 14 At present, CBT modalities have emerged as an important option in the management of IVCT patients due to the larger clot burden in the IVC. 2,13 As the findings, our present study demonstrated that CBTs with/without CDT were safe and effective as first-line endovascular modalities in patients with IVCT. CBTs had distinct advantages of accelerated reduction of clot burden in a moderate time, speedy restoration of blood flow, reduced thrombolytic drug requirement, and lower minor bleeding complication, but potentially increased risk of recoverable AKI and economic cost compared to CDT alone. In contrast, primary CDT had a lower risk of AKI but increased bleeding complications (primarily minor bleeding). Moreover, subgroup analyses between ART and LLCA revealed comparable outcomes with different adverse event profiles.
Definitive studies comparing CBT and CDT for IVCT are not available. The largest prospective randomized clinical trials, such as CaVenT 15 and ATTRACT, 16 have rarely investigated CBTs or CDT for patients with IVCT as a distinct entity, as IVCT is often classified as proximal DVT. Alkhouli et al 17 compared CDT plus anticoagulation versus anticoagulation alone in the treatment of 563 patients with IVCT, demonstrated no significant difference in mortality between CDT and anticoagulation alone. However, bleeding events and resource utilization were higher in CDT therapy. Ye et al 18 described the successful use of ART for the treatment of symptomatic acute and subacute IVCT, indicating that the ART was safe and effective in thrombus removal. In the present study, we utilized CBTs with/without CDT compared with CDT alone to determine the outcomes, it appeared that CBTs were safe and effective as ET modalities in eligible patients with symptomatic IVCT, with high levels of technical success and clinical success, symptoms alleviation, and a low prevalence of minor complication, recurrent VTE and PTS. This implies that it may be reasonable and valuable to extend the utility of CBTs as first-line therapy in IVCT patients.
The distinctions between ART and LLCA in patients with IVCT are largely unknown, and most information has been speculated from studies concerning LEDVT. Oǧuzkurt et al 19 described that the thrombus removal rate (≥50%) of LLCA coupled with CDT in patients with LEDVT was 96.6%, and the incidences of minor and major bleeding complications were 10.1% and 1.4%, respectively. PEARL registry study 20 showed that ART adjunctive with CDT as a treatment modality for LEDVT, resulted in a thrombus removal rate (≥50%) of 96%, and the incidences of minor and major bleeding sequelae were 0.9% and 3.6%, respectively. The subgroup analyses evaluated within patients with IVCT who underwent ART and LLCA showed similar outcomes. Patients assigned to an initial ART tended to have slightly improved thrombus removal grade III and fewer minor complications, as well as recurrent VTE and PTS in the present study. This may be attributed to the fact that these techniques are different in terms of working mechanisms. ART is composed of pharmaco-mechanical effect high-pressure and high-speed injection of lytic drugs, which can fragment and aspirate clots. In contrast, LLCA relies on the manual negative-pressure suction effect, which can have difficulty completely aspirating the thrombus due to limited length and diameter of LLC. LLCA is undeniably a simple and cost-effective strategy, with a lower transient macroscopic hemoglobinuria and recoverable AKI to alleviate IVCT symptoms in a short period of time, but it also has limitations such as excessive intraoperative blood loss compared with ART. 19,20
Despite the utilization of filter devices into IVC to prevent fatal PE of DVT is a well-established option, 21 there is a paucity of data supporting the use of IVCF, and controversies remain as IVCF can lead to various complications. Increased risk of DVT with IVCT have been described, and IVCF-related thrombosis is one of the common adverse events of IVCF placement, which may represent a de novo event or progressive IVCF occlusion due to interception of LEDVT debris. 13 Besides that, complications including filter migration (<1%), fractures (2%-10%), and IVC wall or adjacent organ perforation (0%-41%) have also been observed. 22 Ahmad et al 4 conducted a follow-up study of 1718 cases who underwent IVCF placement, revealing the incidence of IVCF-related thrombosis reached up to 18%. In the present study, we found that the indwelling IVCFs were the major risk factor fostering the required IVCT, which accounted for the majority (56.6%) of IVCT cases. Although the presence or absence of IVCF impacts the outcomes of treatment, there are currently no specific guidelines or recommendations to aid with the standard treatments. Our previous study revealed that both the ART and LLCA have a high thrombus removal rate in IVCF-related iliocaval vein thrombosis. 23 In the present study, CBTs were compared with conventional CDT, indicating that CBTs using ART or LLCA can minimize the dosages of thrombolytic agents and decrease the risk of bleeding complications.
Although acute IVCT is less frequently identified, its related complications are significant and alarming. 22 The GARFIELD-VTE trail demonstrated that IVCT patients had a higher risk of all-cause mortality rate (13.28% vs 4.91%) compared to those patients who underwent LEDVT. 24 Alkhouli et al 17 found that patients treated with CDT had a 1.62-fold higher rate of in-hospital PE than those who underwent anticoagulation, and Nagarsheth et al 14 found that patients who suffered from post-procedure PE may have benefited from a temporary filter. Hence, IVCT may carry a greater risk of lethal PE, and placing a filter may be considered given the more extensive and possible free-floating thrombus. 22 In the present study, we found 33.0% of patients with IVCT had suffered from concomitant PE. Temporary filters were inserted into the IVC above or below the renal vein in 54.7% of patients with extensive thrombus or thrombus exceeding through the tip of the original IVCF that were evaluated as potentially life-threatening prior to further treatments. The results indicated that no patient experienced PE or PE related-death. All newly placed filters and 17 previous placed filters that were still in use were retrieved when feasible to avoid an increased incidence of IVCT in the future.
With respect to the 22 patients with IVCT associated with bilateral LEDVT, bilateral CBTs coupled with adjunctive CDT or CDT alone were used in the present study, which was similar to the description by Nagarsheth et al. 14 We maintained a similar total dose of rt-PA compared with unilateral LEDVT by reducing the unilateral catheter infusion by half, which also yielded very good angiographic and clinical results. At the completion venogram after CBTs treatment, there was no need for IVC stenting due to the acuity of the thrombus and adequate patency. Although the hypothesis that long term outcomes would improve with ETs, judicious use of in-time anticoagulant therapy can serve as a cornerstone to promote the prognosis and decrease the risk of thrombosis recurrence. 1,2,6 When considering anticoagulant medications, we are faced with options of one kind or another. Unfractionated or LWMH is commonly applied, followed by oral anticoagulants. With the accumulation of experience, LWMH was used as anticoagulant for patients without HIT during hospitalization in the present study, and novel oral anticoagulants were not available until 2016, therefore, there were mixed applications between warfarin and rivaroxaban in our out-hospital patients. In the present study, we observed a decrease in recurrent VTE compared to previous study. 6,15,16
It should be noted that this study has several limitations. For a start, catheters used in the present study were not specifically designed for the large space of the IVC, except for the 6F ART and 8F LLC, other diameters of catheters were unavailable at that time. A more powerful 8F ZelanteDVT catheter may be more effective, 14 but some patients who used it were not included in this study. Future mechanical thrombectomy devices that can potentially treat patients with a higher bleeding risk and minimize expenditures through avoidance of fibrinolytic agents should be considered. 8 Another, the drawbacks of selective basis may exist, as some patients were transferred from other hospitals due to limited medical conditions, and oncological patients were excluded. A third, this study is limited to an early short-range observation, and some PTS may present beyond a longer follow-up. Available long-term follow-up data will continue to be recorded. Moreover, given that our study was limited by a result of the small numbers of cases, a relatively low follow-up rate, and other undefined risk factors, the conclusions should be interpreted with caution. In addition, a well-designed prospective trial with a longer follow-up period is warranted to determine the benefit of ETs for quality of life, performance status, and long-term PTS in IVCT patients.
Conclusion
CBTs coupled with/without CDT are safe and effective as first-line ETs in patients with IVCT, reducing clot burden in a moderate time, restoring blood flow rapidly, minimizing thrombolytic drug requirement, and lowering minor bleeding complication compared to CDT alone. However, they may pose a potentially increased risk of recoverable AKI. Conventional CDT has comparable outcomes with lower risk of AKI, but an increased risk of bleeding complications. In terms of CBT modalities, ART and LLCA have comparable outcomes but different adverse event profiles.
Footnotes
Authors’ Note
Maofeng Gong and Qing Zhao share first authorship. The datasets generated and analyzed during the current study are not publicly available, as the experimental data are related to other experiments that are progressing but are available from the corresponding author upon reasonable request. The study protocol was reviewed and approved by the institutional review board (IRB) of the Nanjing First Hospital, Nanjing Medical University (Nanjing, China). In addition, the study was performed in accordance with the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies. The content of the manuscript is original, and it has not been published or accepted for publication.
Author Contributions
MFG and QZ contributed to this project development, manuscript writing/editing. RJ and ZLL contributed to data collection, manuscript associated editing. JK contributed to data analysis. BXZ and XH contributed to manuscript editing. JPG contributed to project development, manuscript editing. All authors contributed to the article and approved the submitted version.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Natural Science Foundation of China (81871463) and Xinghuo Talent Program of Nanjing First Hospital.
