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Journal of Vascular Surgery May 2023Postoperative morbidity in patients undergoing lower extremity amputation (LEA) has remained high. Studies investigating the influence of the anesthetic modality on the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Postoperative morbidity in patients undergoing lower extremity amputation (LEA) has remained high. Studies investigating the influence of the anesthetic modality on the postoperative outcomes have yielded conflicting results. The aim of our study was to assess the effects of regional anesthesia vs general anesthesia on postoperative complications for patients undergoing LEA.
METHODS
We systematically searched PubMed, Embase, MEDLINE, Web of Science, and Google Scholar from 1990 to 2022 for studies investigating the effect of the anesthetic modality on the postoperative outcomes after LEA. Regional anesthesia (RA) included neuraxial anesthesia and peripheral nerve blocks. The outcomes included 30-day mortality, respiratory failure (unplanned postoperative intubation, failure to wean, mechanical ventilation >24 hours), surgical site infection, cardiac complications, urinary tract infection, renal failure, sepsis, venous thrombosis, pneumonia, and myocardial infarction.
RESULTS
Of the 25 studies identified, we included 10 retrospective observational studies with 81,736 patients, of whom 69,754 (85.3%) had received general anesthesia (GA) and 11,980 (14.7%) had received RA. In the GA group, 50,468 patients were men (63.8%), and in the RA group, 7813 patients were men (62.3%). The results of the meta-analyses revealed that GA was associated with a higher rate of respiratory failure (odds ratio, 1.38; 95% confidence interval, 1.06-1.80; P = .02) and sepsis (odds ratio, 1.21; 95% confidence interval, 1.11-1.33; P < .0001) compared with RA. No differences were found in postoperative 30-day mortality, surgical site infection, cardiac complications, urinary tract infection, renal failure, venous thrombosis, pneumonia, and myocardial infarction between the GA and RA groups.
CONCLUSIONS
The results of our meta-analysis have shown that GA could be associated with a higher rate of respiratory failure and sepsis compared with RA for LEA.
Topics: Male; Humans; Female; Surgical Wound Infection; Retrospective Studies; Treatment Outcome; Anesthesia, Conduction; Amputation, Surgical; Pneumonia; Myocardial Infarction; Anesthesia, General; Lower Extremity; Respiratory Insufficiency; Postoperative Complications
PubMed: 36243265
DOI: 10.1016/j.jvs.2022.10.005 -
Journal of Vascular Surgery May 2023No consensus has yet been reached regarding the optimal treatment of patients with thromboangiitis obliterans (TO) and chronic limb ischemia. In the present study, we... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
No consensus has yet been reached regarding the optimal treatment of patients with thromboangiitis obliterans (TO) and chronic limb ischemia. In the present study, we aimed to summarize the results on endovascular treatment of such patients.
METHODS
We performed a meta-analysis using the following databases: PubMed, Scopus, and the Cochrane Library. The eligible studies had been reported up to December 2021 and had evaluated endovascular angioplasty to treat patients with TO and chronic limb ischemia. The early (mortality and technical success) and late (primary/secondary patency and limb salvage) outcomes were evaluated. StatsDirect (StatsDirect Ltd, Merseyside, UK) was used for the statistical analysis.
RESULTS
Overall, 15 eligible studies were included (only endovascular in 11 studies and both endovascular and open repair in 4 studies). Among 601 patients, 402 endovascular procedures (416 limbs) were recorded (angioplasty plus stenting for 7.2% and angioplasty plus thrombolysis for 3.7%). The clinical presentation was intermittent claudication (stage II-III) for 7.9% of the patients and critical ischemia (stage IV-VI) for 92.1% of the patients. Most of the patients had had lesions below the knee, and five had had upper extremity lesions. The pooled technical success rate was 86% (range, 81.1%-90.3%), with no in-hospital mortality. The other complications included perforations (1.9%), wound complications (2.2%), and distal embolism (0.2%). Primary patency was 65.7% (range, 52.7%-77.6%) at 12 months and 50.7% (range, 23.3%-77.9%) at 36 months. Secondary patency was 76.2% (range, 57.5%-90.8%) at 12 months and 64.5% (range, 32.3%-90.6%) at 36 months. The limb salvage rate was 94.1% (range, 90.7%-96.7%) at 12 months and 89.1% (range, 80.6%-95.4%) at 36 months.
CONCLUSIONS
Endovascular angioplasty for patients with TO and chronic limb ischemia was associated with optimal safety and low complication rates. The technical success and late outcomes were acceptable.
Topics: Humans; Thromboangiitis Obliterans; Angioplasty, Balloon; Angioplasty; Peripheral Vascular Diseases; Arterial Occlusive Diseases; Ischemia; Limb Salvage; Vascular Patency; Retrospective Studies; Treatment Outcome
PubMed: 36174815
DOI: 10.1016/j.jvs.2022.09.017 -
Journal of Endovascular Therapy : An... Apr 2024Infrapopliteal lesions are generally complex to treat due to small vessel diameter, long lesion length, multilevel disease, and severe calcification. Therefore,... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Infrapopliteal lesions are generally complex to treat due to small vessel diameter, long lesion length, multilevel disease, and severe calcification. Therefore, different vessel preparation devices have been developed to contribute to better peri- and postprocedural outcomes. This systematic review aims to compare different vessel preparation techniques prior to plain old balloon angioplasty (POBA) or drug-coated balloon (DCB) angioplasty with POBA or DCB alone in infrapopliteal arterial disease.
METHODS
Medline, EMBASE, and Cochrane databases were searched for studies published between 2000 and 2022 assessing the value of adjunctive vessel preparation in infrapopliteal arterial disease. The primary outcomes were 12-month primary patency and limb salvage.
RESULTS
A total of 1685 patients with 1913 lesions were included in 11 POBA studies. Methodological quality was assessed as poor to moderate in these studies. Only 2 studies with 144 patients assessed vessel preparation in conjunction with DCB angioplasty. These randomized trials were assessed as high quality and found no significant benefit of adjunctive atherectomy to DCB angioplasty. The pooled Kaplan-Meier estimates of 12-month primary patency and limb salvage in the POBA studies were 67.8% and 80.9% for POBA, 62.1% and 86.4% for scoring balloons, 67.9% and 79.6% for mechanical atherectomy (MA), and 79.7% and 82.6% for laser atherectomy, respectively. Within the pooled data only scoring balloons and MA demonstrated significantly improved 12-month limb salvage compared to POBA.
CONCLUSIONS
Different forms of adjunctive vessel preparation demonstrate similar 12-month outcomes compared to POBA and DCB angioplasty alone in infrapopliteal disease, with the exception of improved 12-month limb salvage in scoring balloons and MA. However, since the included studies were heterogeneous and assessed as poor to moderate methodological quality, selection bias may have played an important role. Main conclusion is that this systematic review found no additional value of standard use of vessel preparation.
CLINICAL IMPACT
Infrapopliteal arterial disease is associated with chronic limb-threatening ischemia (CLTI) and generally complex to treat due to small vessel diameter, long lesion length, multilevel disease and severe calcification. A wide range of vessel preparation devices have been developed to contribute to improved peri- and postprocedural outcomes in these complex lesions. This systematic review aims to compare different vessel preparation techniques prior to plain old balloon angioplasty (POBA) or drug coated balloon (DCB) angioplasty with POBA or DCB angioplasty alone in infrapopliteal arterial disease. Different forms of adjunctive vessel preparation demonstrate similar 12-month outcomes compared to POBA and DCB angioplasty alone in infrapopliteal disease, with the exception of improved 12-month limb salvage in scoring balloons and mechanical atherectomy (MA). However, since the included studies were heterogeneous and assessed as poor to moderate methodological quality, selection bias may have played an important role. Main conclusion is that this systematic review found no additional value of standard use of vessel preparation.
Topics: Humans; Femoral Artery; Popliteal Artery; Peripheral Arterial Disease; Risk Factors; Treatment Outcome; Angioplasty, Balloon; Coated Materials, Biocompatible; Vascular Patency
PubMed: 36062761
DOI: 10.1177/15266028221120752 -
Anatolian Journal of Cardiology Oct 2022Nonbacterial thrombotic endocarditis is characterized by the presence of organized thrombi on cardiac valves, often associated with hypercoagulable states. There is a...
BACKGROUND
Nonbacterial thrombotic endocarditis is characterized by the presence of organized thrombi on cardiac valves, often associated with hypercoagulable states. There is a paucity of data regarding the predictors of mortality in patients with nonbacterial thrombotic endocarditis. Our primary aim was to identify predictors of in-hospital mortality in patients with nonbacterial thrombotic endocarditis.
METHODS
A systematic literature review of all published cases and case series was performed until May 2018 according to Preferred Reporting Items for Systematic Review and Meta-analyses statement guidelines. We applied random forest machine learning model to identify predictors of in-patient mortality in patients with nonbacterial thrombotic endocarditis.
RESULTS
Our search generated a total of 163 patients (mean age, 46 ± 17 years; women, 69%) with newly diagnosed nonbacterial thrombotic endocarditis. The in-hospital mortality rate in the study cohort was 30%. Among the patients who died in the hospital, initial presentation of pulmonary embolism (12.2 vs. 2.6%), splenic (38.7 vs. 10.5%), and renal (40.8 vs. 9.6%) infarcts were higher compared to patients alive at the time of discharge. Higher rates of malignancy (71.4 vs. 39.4%, P = .0003) and lower rates of antiphospholipid syndrome (8.1 vs. 48.2%, P = .0001) were noted in deceased patients. Random forest machine learning analysis showed that older age, presence of antiphospholipid syndrome, splenic infarct, renal infarct, peripheral thromboembolism, pulmonary embolism, myocardial infarction, and mitral valve regurgitation were significantly associated with increased risk of in-hospital mortality.
CONCLUSION
Patients admitted with nonbacterial thrombotic endocarditis have a high rate of in-hospital mortality. Factors including older age, presence of antiphospholipid syndrome, splenic/renal infarct, lower limb thromboembolism, pulmonary embolism, myocardial infarction, and mitral valve regurgitation were significantly associated with increased risk of in-hospital mortality in patients with nonbacterial thrombotic endocarditis.
Topics: Adult; Antiphospholipid Syndrome; Endocarditis, Non-Infective; Female; Humans; Middle Aged; Mitral Valve Insufficiency; Myocardial Infarction; Pulmonary Embolism; Thromboembolism
PubMed: 36052565
DOI: 10.5152/AnatolJCardiol.2022.1282 -
Hellenic Journal of Cardiology : HJC =... 2023Patients with mitral stenosis (MS) may be predisposed to acute cerebrovascular events (ACE) and peripheral thromboembolic events (TEE). Concomitant atrial fibrillation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with mitral stenosis (MS) may be predisposed to acute cerebrovascular events (ACE) and peripheral thromboembolic events (TEE). Concomitant atrial fibrillation (AF), mitral annular calcification (MAC) and rheumatic heart disease (RHD) are independent risk factors. Our aim was to evaluate the incidence of ACEs in MS patients and the implications of AF, MAC and RHD on thromboembolic risks.
METHODS
This systematic review was registered on PROSPERO (CRD42021291316). Six databases were searched from inception to 19th December 2021. The clinical outcomes were composite ACE, ischaemic stroke/transient ischaemic attack (TIA) and peripheral TEE.
RESULTS
We included 16 and 9 papers, respectively, in our qualitative and quantitative analyses. The MS cohort with AF had the highest incidence of composite ACE (31.55%; 95% CI 3.60-85.03; I = 99%), followed by the MAC (14.85%; 95% CI 7.21-28.11; I = 98%), overall MS (8.30%; 95% CI 3.45-18.63; I = 96%) and rheumatic MS population (4.92%; 95% CI 3.53-6.83; I = 38%). Stroke/TIA were reported in 29.62% of the concomitant AF subgroup (95% CI 2.91-85.51; I = 99%) and in 7.11% of the overall MS patients (95% CI 1.91-23.16; I = 97%). However, the heterogeneity of the pooled incidence of clinical outcomes in all groups, except the rheumatic MS group, was substantial and significant. The logit-transformed proportion of composite ACE increased by 0.0141 (95% CI 0.0111-0.0171; p < 0.01) per year of follow-up.
CONCLUSION
In the MS population, MAC and concomitant AF are risk factors for the development of ACE. The scarcity of data in our systematic review reflects the need for further studies to explore thromboembolic risks in all MS subtypes.
Topics: Humans; Mitral Valve Stenosis; Ischemic Attack, Transient; Incidence; Brain Ischemia; Stroke; Heart Valve Diseases; Rheumatic Heart Disease; Atrial Fibrillation; Thromboembolism
PubMed: 36041698
DOI: 10.1016/j.hjc.2022.08.002 -
Drugs Aug 2022High-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or acetylsalicylic acid (ASA) plus low-dose rivaroxaban is lacking. Therefore, we conducted a network meta-analysis on the effectiveness of all antithrombotic regimens studied in PAD.
METHODS
A systematic search was conducted to identify randomized controlled trials. The primary endpoints were major adverse cardiovascular events (MACE) and major bleedings. Secondary endpoints were major adverse limb events (MALE) and acute limb ischaemia (ALI). For each outcome, a frequentist network meta-analysis was used to compare relative risks (RRs) between medication and ASA. ASA was the universal comparator since a majority of studies used ASA as in the reference group.
RESULTS
Twenty-four randomized controlled trials were identified including 48,759 patients. With regard to reducing MACE, clopidogrel [RR 0.78, 95% confidence interval (CI) 0.66-0.93], ticagrelor (RR 0.79, 95% CI 0.65-0.97), ASA plus ticagrelor (RR 0.79, 95% CI 0.64-0.97), and ASA plus low-dose rivaroxaban (RR 0.84, 95% CI 0.76-0.93) were more effective than ASA, and equally effective to one another. As compared to ASA, major bleedings occurred more frequently with vitamin K antagonists, rivaroxaban, ASA plus vitamin K antagonists, and ASA plus low-dose rivaroxaban. All regimens were similar to ASA concerning MALE, while ASA plus low-dose rivaroxaban was more effective in preventing ALI (RR 0.67, 95% CI 0.55-0.80). Subgroup analysis in patients undergoing peripheral revascularization revealed that ≥ 3 months after intervention, evidence of benefit regarding clopidogrel, ticagrelor, and ASA plus ticagrelor was lacking, while ASA plus low-dose rivaroxaban was more effective in preventing MACE (RR 0.87, 95% CI 0.78-0.97) and MALE (RR 0.89, 95% CI 0.81-0.97) compared to ASA. ASA plus clopidogrel was not superior to ASA in preventing MACE ≥ 3 months after revascularization. Evidence regarding antithrombotic treatment strategies within 3 months after a peripheral intervention was lacking.
CONCLUSION
Clopidogrel, ticagrelor, ASA plus ticagrelor, and ASA plus low-dose rivaroxaban are superior to ASA monotherapy and equally effective to one another in preventing MACE in PAD. Of these four therapies, only ASA plus low-dose rivaroxaban provides a higher risk of major bleedings. More than 3 months after peripheral vascular intervention, ASA plus low-dose rivaroxaban is superior in preventing MACE and MALE compared to ASA but again at the cost of a higher risk of bleeding, while other treatment regimens show non-superiority. Based on the current evidence, clopidogrel may be considered the antithrombotic therapy of choice for most PAD patients, while in patients who underwent a peripheral vascular intervention, ASA plus low-dose rivaroxaban could be considered for the long-term (> 3 months) prevention of MACE and MALE.
Topics: Aspirin; Clopidogrel; Fibrinolytic Agents; Hemorrhage; Humans; Network Meta-Analysis; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Ticagrelor; Vitamin K
PubMed: 35997941
DOI: 10.1007/s40265-022-01756-6 -
Journal of Vascular Surgery Mar 2023The objective of this study was to evaluate the application of the Global Anatomic Staging System (GLASS) in the endovascular treatment of chronic limb-threatening... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective of this study was to evaluate the application of the Global Anatomic Staging System (GLASS) in the endovascular treatment of chronic limb-threatening ischemia (CLTI).
METHODS
We performed systematic research between June 2019 and February 2022, including articles investigating the relationship of GLASS classification with the outcomes of endovascular interventions in the treatment of CLTI. Data from the included studies were pooled and meta-analyzed. The primary endpoints were limb-based patency (LBP) at 1-year follow-up and immediate technical failure (ITF). Secondary endpoints included major amputation. We performed subgroup analysis between studies that reported on calcium modifier inclusion during GLASS classification and studies that did not.
RESULTS
Eleven studies, including 1816 patients (1975 limbs) met the inclusion criteria. The pooled ITF rates for GLASS stages I, II, and III are 5.52% (95% confidence interval [CI], 3.74%-8.07%), 7.39% (95% CI, 5.32%-10.18%), and 21.07% (95% CI, 13.48%-31.39%) respectively. The pooled LBP for GLASS stages I, II, and III are 68.43% (95% CI, 53.44%-80.37%), 41.52% (95% CI, 18.91%-68.37%), and 38.64% (95% CI, 19.83%-61.57%). The relative risk (RR) for ITF regarding composite GLASS I and II stages vs GLASS III is 3.96 (95% CI, 1.96-7.98). The RR for LBP of GLASS I and II versus GLASS stage III is 1.51 (95% CI, 0.86-2.64). Pooled major amputation rates for the composite GLASS I, II and GLASS III stages are 7.62% (95% CI, 5.44%-10.58%) and 15.43% (95% CI, 11.72%-20.05%) respectively, whereas the RR between GLASS I, II, and GLASS III stages is 1.84 (95% CI, 1.18-2.87).
CONCLUSIONS
Our study demonstrated that patients with CLTI undergoing endovascular interventions classified as GLASS stage III had almost a four-fold risk increase for ITF and 1.84 times the risk of major amputation compared with stages I and II. Additionally, GLASS classification correctly predicted ITF for all three stages, whereas it failed to predict stage I and II LBP outcomes. Safe conclusions regarding LBP cannot be drawn due to the low quality and small number of the included studies, necessitating further research. Furthermore, we displayed the importance of calcium moderator inclusion in the accurate classification of GLASS.
Topics: Humans; Chronic Limb-Threatening Ischemia; Endovascular Procedures; Treatment Outcome; Calcium; Risk Factors; Limb Salvage; Ischemia; Peripheral Arterial Disease; Retrospective Studies; Chronic Disease
PubMed: 35953002
DOI: 10.1016/j.jvs.2022.07.183 -
European Journal of Vascular and... Dec 2022To assess the comparative effectiveness and temporal changes in quality of life (QoL) outcomes after revascularisation, major lower extremity amputation (MLEA), and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the comparative effectiveness and temporal changes in quality of life (QoL) outcomes after revascularisation, major lower extremity amputation (MLEA), and conservative management (CM) in chronic limb threatening ischaemia (CLTI).
DATA SOURCES
MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science.
REVIEW METHODS
A systematic review and meta-analysis were performed on QoL measured by any QoL instrument in adult patients with CLTI after open surgery (OS), endovascular intervention (EVI), MLEA, or CM. Randomised controlled trials and prospective observational studies published in any language between 1 January 1990 and 21 May 2021 were included. There was a pre-specified measurement time point of six months. Random effects meta-analysis was conducted on total scores for each QoL instrument. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach (PROSPERO registration: CRD42021253953).
RESULTS
Fifty-five studies with 8 909 patients were included. There was significant heterogeneity in the methods used to measure QoL, and the study characteristics. In particular, 14 different QoL instruments were used with various combinations of disease specific and generic instruments within each study. A narrative summary is therefore presented. Comparative effectiveness data showed there was reasonable certainty that QoL was similar between OS and EVI at six months. Temporal outcomes suggested small to moderate improvements in QOL six months after OS and EVI compared with baseline. Limited data indicated that QoL can be maintained or slightly improved after MLEA or CM. Treatment effects were overestimated owing to small study effects, selective non-reporting, attrition, and survivorship bias.
CONCLUSION
QoL after OS and EVI appears to be similar. Revascularisation may provide modest QoL benefits, while MLEA or CM can maintain QoL. However, certainty of evidence is generally low or very low, and interpretation is hampered by significant heterogeneity. There is a need for a CLTI specific QoL instrument and methodological standardisation in QoL studies.
Topics: Humans; Quality of Life; Chronic Limb-Threatening Ischemia; Amputation, Surgical; Vascular Surgical Procedures; Conservative Treatment; Observational Studies as Topic
PubMed: 35952907
DOI: 10.1016/j.ejvs.2022.07.051 -
Medicine Jul 2022There are limited data on the optimal timing and frequency of postpartum follow-up visits after hypertensive disorders of pregnancy (HDP) for primary prevention and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
There are limited data on the optimal timing and frequency of postpartum follow-up visits after hypertensive disorders of pregnancy (HDP) for primary prevention and early detection of cardiovascular diseases (CVDs) in high-risk women. We aimed to evaluate the risk of cardiovascular outcomes later in life in women with prior HDP in different years postpartum and in preeclamptic women with severe features, or early onset of preeclampsia.
METHODS
We searched MEDLINE, Cochrane Library, Web of Science, and Scopus without language restriction for relevant articles published from inception to March 16, 2022. We included prospective and retrospective cohort studies assessing hypertension, ischemic heart disease, heart failure, venous thromboembolism, peripheral vascular disease, stroke, dementia, composite cardiovascular and/or cerebrovascular diseases, and mortality after 6 weeks postpartum, in women with prior HDP compared with controls. Two authors independently selected and appraised the studies. Article quality was independently assessed using the Newcastle-Ottawa Scale (NOS). Random-effect models were used for meta-analysis. Stratified analyses based on years postpartum, severity, and onset of preeclampsia were performed.
RESULTS
We included 59 studies for qualitative review, of which 56 were included in quantitative meta-analysis, involving 1,262,726 women with prior HDP and 14,711,054 controls. Women with prior HDP had increased risks of hypertension (relative risk [RR] 3.46, 95% confidence interval [CI]: 2.67-4.49), ischemic heart disease (RR 2.06, 95% CI: 1.38-3.08), and heart failure (RR 2.53, 95% CI: 1.28-5.00) later in life, compared with those with normotensive pregnancies. The risk of hypertension was highest during 5 years postpartum (RR 5.34, 95% CI: 2.74-10.39). Compared with normotensive pregnancies, the risk of future CVDs significantly increased in preeclamptic women.
DISCUSSION
A history of HDP is associated with approximately 2- to 4-fold increase in the risk of CVDs. Screening for CVDs and their risk factors in women with prior HDP since delivery, especially the first 5 years after delivery is suggested for early detection and appropriate management. Evidence on the risks of CVDs in preeclampsia with severe features and early onset of preeclampsia is limited due to having few studies and high heterogeneity.
FUNDING
The Royal Golden Jubilee PhD Program-RGJ (PHD/0183/2561); Thailand Science Research and Innovation (TSRI) Research Career Development Grant-RSA (RSA6180009); Targeted Research Grants Program of the Faculty of Medicine, Prince of Songkla University, Thailand.
REGISTRATION
CRD42020191550.
Topics: Cardiovascular Diseases; Female; Heart Failure; Humans; Hypertension, Pregnancy-Induced; Myocardial Ischemia; Postpartum Period; Pre-Eclampsia; Pregnancy; Prospective Studies; Retrospective Studies
PubMed: 35905265
DOI: 10.1097/MD.0000000000029646 -
The Cochrane Database of Systematic... Jul 2022Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients, the disease progresses to critical limb ischaemia (CLI), also known as critical... (Review)
Review
BACKGROUND
Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients, the disease progresses to critical limb ischaemia (CLI), also known as critical limb-threatening ischaemia. In a substantial number of individuals with CLI, no effective treatment options other than amputation are available, with around a quarter of these patients requiring a major amputation during the following year. This is the second update of a review first published in 2011.
OBJECTIVES
To evaluate the benefits and harms of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for CLI.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 8 November 2021.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention, conventional conservative therapy, or placebo).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes of interest were all-cause mortality, pain, and amputation. Our secondary outcomes were angiographic analysis, ankle-brachial index (ABI), pain-free walking distance, side effects and complications. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included four RCTs involving a total of 176 participants with a clinical diagnosis of CLI. Participants were randomised to receive either intramuscular cell implantation of BMMNCs or control. The control arms varied between studies, and included conventional therapy, diluted autologous peripheral blood, and saline. There was no clear evidence of an effect on mortality related to the administration of BMMNCs compared to control (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.15 to 6.63; 3 studies, 123 participants; very low-certainty evidence). All trials assessed changes in pain severity, but the trials used different forms of pain assessment tools, so we were unable to pool data. Three studies individually reported that no differences in pain reduction were observed between the BMMNC and control groups. One study reported that reduction in rest pain was greater in the BMMNC group compared to the control group (very low-certainty evidence). All four trials reported the rate of amputation at the end of the study period. We are uncertain if amputations were reduced in the BMMNC group compared to the control group, as a possible small effect (RR 0.52, 95% CI 0.27 to 0.99; 4 studies, 176 participants; very low-certainty evidence) was lost after undertaking sensitivity analysis (RR 0.52, 95% CI 0.19 to 1.39; 2 studies, 89 participants). None of the included studies reported any angiographic analysis. Ankle-brachial index was reported differently by each study, so we were not able to pool the data. Three studies reported no changes between groups, and one study reported greater improvement in ABI (as haemodynamic improvement) in the BMMNC group compared to the control group (very low-certainty evidence). One study reported pain-free walking distance, finding no clear difference between BMMNC and control groups (low-certainty evidence). We pooled the data for side effects reported during the follow-up, and this did not show any clear difference between BMMNC and control groups (RR 2.13, 95% CI 0.50 to 8.97; 4 studies, 176 participants; very low-certainty evidence). We downgraded the certainty of the evidence due to the concerns about risk of bias, imprecision, and inconsistency.
AUTHORS' CONCLUSIONS
We identified a small number of studies that met our inclusion criteria, and these differed in the controls they used and how they measured important outcomes. Limited data from these trials provide very low- to low-certainty evidence, and we are unable to draw conclusions to support the use of local intramuscular transplantation of BMMNC for improving clinical outcomes in people with CLI. Evidence from larger RCTs is needed in order to provide adequate statistical power to assess the role of this procedure.
Topics: Adult; Amputation, Surgical; Bone Marrow; Humans; Ischemia; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Transplantation, Autologous
PubMed: 35802393
DOI: 10.1002/14651858.CD008347.pub4