Systematic Review and Meta-Analysis of the Impact of Surgeon-Physician Co-management Models on Short Term Outcomes for Vascular Surgery Inpatients.

OBJECTIVE: As the population ages, vascular surgeons are treating progressively older, multimorbid patients at risk of peri-operative complications. An embedded physician has been shown to improve outcomes in general and orthopaedic surgery. This systematic review and meta-analysis aimed to investigate the impact of surgeon-physician co-management models on morbidity and mortality in vascular inpatients. DATA SOURCES: PubMed, Scopus, Embase, conference abstract listings, and clinical trial registries. REVIEW METHODS: Studies comparing adult vascular surgery inpatients under co-management with "standard of care" were eligible. The relative risks (RRs) of mortality, medical complications, and 30 day re-admission between co-management and standard care were calculated. The effect of co-management on the mean length of stay was calculated using weighted means. Risk of bias was assessed using the Methodological Index for Non-Randomised Studies, and certainty assessment with the GRADE analysis tools. RESULTS: No randomised trials were identified. Eight single institution studies between 2011 and 2020 with 7 410 patients were included. All studies were observational using before-after methodology. Studies were of high to moderate risk of bias, and outcomes were of very low GRADE certainty of evidence. Co-management was associated with a statistically significantly lower relative risk of mortality (RR 0.64, 95% confidence interval [CI] 0.44 - 0.92; p = .02), cardiac complications (RR 0.47, 95% CI 0.25 - 0.87; p = .02), and infective complications (RR 0.49, 95% CI 0.35 - 0.67; p < .001) in vascular inpatients. No statistically significant differences in length of stay (MD -0.6 days, 95% CI -1.44 - 0.24 days; p = .16) and 30 day re-admission (RR 0.96, 95% CI 0.84 - 1.08; p = .49) were noted. CONCLUSION: Early results of physician and surgeon co-management for vascular surgery inpatients showed promising results from very low certainty data. Further well designed, prospective studies are needed to determine how to maximise the impact of physicians within a vascular service to improve patient outcomes while effectively using hospital resources.

Systematic Review and Meta-Analysis of Nonoperative Management for SVS Grade II Blunt Traumatic Aortic Injury.

BACKGROUND: Society for Vascular Surgery (SVS) grade II blunt traumatic aortic injury is defined as intramural hematoma with or without external contour abnormality. It is uncertain whether this aortic injury pattern should be treated with endovascular stent-grafting or nonoperative measures. Since the adoption of the SVS Guidelines on endovascular repair of blunt traumatic aortic injury, the practice pattern for management of grade II injuries has been heterogenous. The objective of the study was to report natural history outcomes of grade II blunt traumatic aortic injury. METHODS: A systematic review of published traumatic aortic injury studies was performed. Online database searches were current to November 2022. Eligible studies included data on aortic injuries that were both managed nonoperatively and classified according to the SVS 2011 Guidelines. Data points on all-cause mortality, aorta-related mortality and early aortic intervention were extracted and underwent meta-analysis. The methodology was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. RESULTS: Thirteen studies were included in the final analysis with a total of 204 cases of SVS grade II blunt traumatic aortic injury treated nonoperatively. The outcomes rates were estimated at 10.4% (95% confidence interval [CI] 6.7%-14.9%) for all-cause mortality, 2.9% (95% CI 1.1%-5.7%) for aorta-related mortality, and 3.3% (95% CI 1.4%-6.2%) for early aortic intervention. The studies included in the analysis were of fair quality with a mean Downs and Black score 15 (±1.8). CONCLUSIONS: Grade II blunt traumatic aortic injury follows a relatively benign course with few instances of aortic-related mortality. Death in the setting of this injury pattern is more often attributable to sequelae of multisystem trauma and not directly related to aortic injury. The current data support nonoperative management and imaging surveillance for grade II blunt traumatic aortic injury instead of endovascular repair. Longer-term effects on the aorta at the site of injury are unknown.

Editor's Choice - Systematic Review and Meta-Analysis of Lower Extremity Vascular Complications after Arterial Access for Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA): An Inevitable Concern?

OBJECTIVE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to temporise non-compressible torso haemorrhage. Recent data have suggested that vascular access complications secondary to REBOA placement are higher than initially anticipated. This updated systematic review and meta-analysis aimed to determine the pooled incidence rate of lower extremity arterial complications after REBOA. DATA SOURCES: PubMed, Scopus, Embase, conference abstract listings, and clinical trial registries. REVIEW METHODS: Studies including more than five adults undergoing emergency REBOA for exsanguinating haemorrhage that reported access site complications were eligible for inclusion. A pooled meta-analysis of vascular complications was performed using the DerSimonian-Laird weights for the random effects model, presented as a Forest plot. Further meta-analyses compared the relative risk of access complications between different sheath sizes, percutaneous access techniques, and indications for REBOA. Risk of bias was assessed using the Methodological Index for Non-Randomised Studies (MINORS) tool. RESULTS: No randomised controlled trials were identified, and the overall study quality was poor. Twenty-eight studies including 887 adults were identified. REBOA was performed for trauma in 713 cases. The pooled proportion rate of vascular access complications was 8.6% (95% confidence interval 4.97 - 12.97), with substantial heterogeneity (I2 = 67.6%). There was no significant difference in the relative risk of access complications between 7 and > 10 F sheaths (p = .54), or between ultrasound guided and landmark guided access (p = .081). However, traumatic haemorrhage was associated with a significantly higher risk of complications compared with non-traumatic haemorrhage (p = .034). CONCLUSION: This updated meta-analysis aimed to be as comprehensive as possible considering the poor quality of source data and high risk of bias. It suggested that lower extremity vascular complications were higher than originally suspected after REBOA. While the technical aspects did not appear to impact the safety profile, a cautious association could be drawn between REBOA use for traumatic haemorrhage and a higher risk of arterial complications.

Optimal Management of Asymptomatic Carotid Artery Stenosis: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: Management of asymptomatic carotid artery stenosis (ACAS), including carotid endarterectomy (CEA), carotid artery stenting (CAS), and best medical treatment (BMT), remains inconsistent in current practice. Early studies reported a benefit of CEA vs. BMT; however, the current risk-benefit profile of invasive therapy lacks consensus. By evaluating the effects of modern BMT vs. invasive intervention on patient outcomes, this study aimed to influence the future management of ACAS. METHODS: A systematic review and series of network meta-analyses were performed assessing peri-operative (within 30 days) and long term (30 days - 5 years) stroke and mortality risk between ACAS interventions. Total stroke, major, minor, ipsilateral, and contralateral stroke subtypes were assessed independently. Traditional (pre-2000) and modern (post-2000) BMT were compared to assess clinical improvements in medical therapy over the previous two decades. Risks of myocardial infarction (MI) and cranial nerve injury (CNI) were also assessed. RESULTS: Seventeen reports of 14 310 patients with > 50% ACAS were included. CEA reduced the odds of a peri-operative stroke event occurring vs. CAS (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1 - 2.2 [0 - 20 fewer/1 000]). CEA and CAS reduced the long term odds of minor strokes (OR 0.35, 95% CI 0.21 - 0.59 [20 fewer/1 000]) and ipsilateral strokes (OR 0.27, 95% CI 0.19 - 0.39 [30 fewer/1 000]) vs. all BMT. CEA reduced the odds of major strokes and combined stroke and mortality vs. traditional BMT; however, no difference was found between CEA and modern BMT. CAS reduced the odds of peri-operative MI (OR 0.49, 95% CI 0. 26 - 0.91) and CNI (OR 0.07, 95% CI 0.01 - 0.42) vs. CEA. CONCLUSION: Modern BMT demonstrates similar reductions in major stroke, combined stroke, and mortality to CEA. The overall risk reductions are low and data were unavailable to assess subgroups which may benefit from intervention. However, BMT carries the potential to reduce the requirement for surgical intervention in patients with ACAS.

Adipose-derived stem cells in patients with venous ulcers: Systematic review.

OBJECTIVES: Few studies have reported on the safety and durability of adipose-derived stem cells (ADSCs) to support healing in patients with venous leg ulcers (VLU). To establish if there is any evidence to support ADSC use in VLU patients, a systematic review was conducted. METHODS: A systematic review was conducted following the PRISMA guidelines. PubMed and Embase databases were searched for relevant papers. References from retrieved papers were reviewed to identify any extra eligible studies. RESULTS: After duplicate removal, 950 papers were screened for eligibility of which 932 were excluded based on title and abstract. Four papers were included in the final analysis (one randomised study and three non-randomised studies). 66 patients in total received ADSCs for VLU treatment. The only randomised paper reported 6-month healing rates of 75% with ADSCs compared to 50% in controls. 100% healing was achieved in one study. The remaining 2 studies reported 25% and 58% healing; however, they included patients with relatively large VLUs. Pain scores decreased after ADSCs application where reported. No serious procedure related complications were reported. CONCLUSION: ADSCs may enhance ulcer healing in patients with chronic VLU and appears safe based on initial reports. Large, randomised trials are needed to definitively establish the technique's role in VLU patients.

Systematic review of the relationship between Hollenhorst plaques and cerebrovascular events.

BACKGROUND: Few studies have evaluated the association between asymptomatic cholesterol emboli on fundoscopy (known as Hollenhorst plaque) and the subsequent risk of stroke or death.1. AIM: To evaluate the association between the presence of asymptomatic cholesterol retinal emboli and the risk of cerebrovascular events, with assessment of the need for carotid intervention. METHODS: PubMed, Embase, and Cochrane Library databases were searched using appropriate terms. The systematic review was conducted according to PRISMA guidelines. RESULTS: Initial search revealed 43 in Medline and 46 in Embase databases. Twenty-four potentially eligible studies were included after duplicate and non-related studies were excluded based on title and abstract. Three more studies were identified from reference lists. Seventeen studies were included in the final analysis. Asymptomatic cholesterol emboli were present in 1343 patients. Approximately 17.8% (n = 181) had history of either cerebro-vascular Accident (CVA) or transient ischaemic attacks (TIAs) at presentation (more than 6 months). Nine studies mentioned the incidence of cerebrovascular events during follow-up. Of 780 patients, 93 evolved to stroke, TIAs, or death from a major carotid event during the follow-up period (6-86 m), an incidence of about 12%. Death due to stroke was documented in 3 studies (n = 12). CONCLUSION: The presence of asymptomatic retinal emboli indicates a risk of a cerebrovascular event when compared to patients with no plaques seen on fundoscopy. The evidence suggests that these patients warrant referral for medical optimization of cardiovascular risk factors. Currently, there is no recommendation to support carotid endarterectomy in patients with Hollenhorst plaques, or retinal emboli, and further studies are needed to assess this.

The role of tranexamic acid in reducing post-operative bleeding and seroma formation in breast surgery: A meta-analysis.

INTRODUCTION: Tranexamic acid (TXA) reduces blood loss and blood transfusion requirements in surgery. Seroma and haematoma formation occur as complications of breast surgery. We aimed to perform a meta-analysis evaluating TXA in reducing post-operative haematoma and seroma formation for breast surgery. METHODS: A systematic review was performed in accordance with PRISMA guidelines. Results were expressed as dichotomous variables pooled as odds ratios (OR) with corresponding 95% confidence intervals (CIs) using the Mantel-Haenszel method. RESULTS: Seven studies including 1446 patients were included. There were 1830 breast surgery procedures performed with TXA administered in 797 cases (43.6%). There was a significant reduction in haematoma rates in the TXA group (TXA: 3.184% (22/691) vs Control: 6.787% (64/943), OR: 0.41, 95% CI: 0.20-0.86, P = 0.020). Based on surgical procedure, haematoma rates were similar for TXA and control groups in cancer surgery (P = 0.230). Haematoma rates reduced following TXA use in cosmetic procedures (TXA: 3.807% (15/394) vs. Control: 9.091% (34/374), OR: 0.41, 95% CI: 0.22-0.75, P = 0.004). Haematoma rates were also reduced in procedures where axillary lymph node dissection (ALND) was not performed; in the TXA group, 3.379% (22/651) developed a haematoma versus 6.623% (60/906) in the control group (OR: 0.45, 95% CI 0.27-0.77, P = 0.003). TXA administration did not impact seroma formation or infection rates. CONCLUSION: Perioperative administration of TXA may impact the incidence of haematoma in breast surgery, particularly in cosmetic procedures and procedures without ALND. Well-designed randomised studies are required to determine its true efficacy. TXA has no effect on seroma formation or infection in breast surgery.

Vascular access device type for systemic anti-cancer therapies: a scoping review protocol.

INTRODUCTION: Vascular access devices (VADs) are the most common invasive procedure performed in acute medicine and cancer patients undergo multiple invasive vascular access procedures. Our aim is to identify the type of evidence available regarding the best choice of VAD for cancer patients undergoing systemic anti-cancer therapy (SACT). In this article, the authors frame the scoping review protocol used, which will systematically report all published and unpublished literature around the use of VADs for the infusion of SACT in oncology. INCLUSION CRITERIA: For studies to be included, they must focus on people or populations aged 18 years or older and report on vascular access in cancer patients. The concept is the variety of VAD use in cancer and reported insertion and post-insertion complications. The context surrounds the intravenous treatment of SACT whether in a cancer centre or non-cancer setting. METHODS: The JBI scoping review methodology framework will guide the conduct of this scoping review. Electronic databases (CINAHL, Cochrane, Medline and Embase) will be searched. Grey literature sources and the reference lists of key studies will be reviewed to identify those appropriate for inclusion. No date limits will be used in the searches and studies will be limited to the English language. Two reviewers will independently screen all titles and abstracts and full-text studies for inclusion, and a third reviewer will arbitrate disagreements. All bibliographic data, study characteristics and indicators will be collected and charted using a data extraction tool.

Outcomes of Saphenous Vein Intervention in the Management of Superficial Venous Incompetence: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To determine the most effective modality of intervention to treat saphenous vein insufficiency. SUMMARY OF BACKGROUND DATA: Endovenous therapies have instigated a paradigm shift in the management of superficial venous incompetence. When compared with open surgery, endovenous interventions (foam sclerotherapy, radiofrequency ablation, endovenous laser ablation (EVLA), mechanochemical ablation, and CAE closure) potentially offer reduced morbidity with similar procedural efficacy. METHODS: A systematic review and series of network meta-analyses of randomized controlled trials were performed assessing risks of procedural failure (within 6-weeks) and recurrence (6-weeks to 5-years), defined by ultrasound, between the different modalities of intervention for superficial venous incompetence. Treatment comparisons addressing risks of common adverse events, venous clinical severity score, and pain were also performed. RESULTS: A systematic search identified 51 articles, describing 36 randomized controlled trials, incorporating 7576 limbs. Outcome data on 10 modalities of intervention were analyzed up to 5-year follow-up. CAE resulted in the lowest risk of procedural failure within 6-weeks. Foam sclerotherapy had the highest risk of recurrence while high ligation with stripping (HLS) and Conservatrice Hemodynamique de l'Insuffisance Veineuse en Ambulatoire were ranked best to reduce long-term recurrence. No intervention increased risks of venous thromboembolism and there was minimal difference in morbidity between treatments. All interventions improved venous clinical severity score (range -1.02 to -4.95), however, radiofrequency ablation demonstrated the greatest improvement, followed by EVLA and HLS between 2 to 5-years. EVLA was associated with the highest risk of pain, while mechanochemical ablation offered the least. CONCLUSIONS: Although CAE offered the lowest risk of initial procedural failure, HLS resulted in lower rates of long-term recurrence without considerably increasing morbidity when compared with other endovenous options.

Marrow changes and reduced proliferative capacity of mesenchymal stromal cells from patients with "no-option" critical limb ischemia; observations on feasibility of the autologous approach from a clinical trial.

BACKGROUND AIMS: Approximately 1 in 3 patients with critical limb ischemia (CLI) are not suitable for surgical or endovascular revascularization. Those "no-option" patients are at high risk of amputation and death. Autologous bone marrow mesenchymal stromal cells (MSCs) may provide a limb salvage option. In this study, bone marrow characteristics and expansion potentials of CLI-derived MSCs produced during a phase 1b clinical trial were compared with young healthy donor MSCs to determine the feasibility of an autologous approach. Cells were produced under Good Manufacturing Practice conditions and underwent appropriate release testing. METHODS: Five bone marrow aspirates derived from patients with CLI were compared with six young healthy donor marrows in terms of number of colony-forming units-fibroblast (CFUF) and mononuclear cells. The mean population doubling times and final cell yields were used to evaluate expansion potential. The effect of increasing the volume of marrow on the CFUF count and final cell yield was evaluated by comparing 5 CLI-derived MSCs batches produced from a targeted 30 mL of marrow aspirate to five batches produced from a targeted 100 mL of marrow. RESULTS: CLI-derived marrow aspirate showed significantly lower numbers of mononuclear cells with no difference in the number of CFUFs when compared with healthy donors' marrow aspirate. CLI-derived MSCs showed a significantly longer population doubling time and reduced final cell yield compared with young healthy donors' MSCs. The poor growth kinetics of CLI MSCs were not mitigated by increasing the bone marrow aspirate from 30 to 100 mL. CONCLUSIONS: In addition to the previously reported karyotype abnormalities in MSCs isolated from patients with CLI, but not in cells from healthy donors, the feasibility of autologous transplantation of bone marrow MSCs for patients with no-option CLI is further limited by the increased expansion time and the reduced cell yield.

Potentially undiagnosed cognitive impairment in patients with peripheral arterial disease: A systematic review of the literature.

INTRODUCTION: It is purported that patients with peripheral arterial disease (PAD) may have impaired cognitive function due to concomitant cerebrovascular disease. Such disease may be clinically unrecognized but can impact on a patient's recovery and prognosis. The purpose of this systematic review was to interrogate the body of published evidence on undiagnosed cognitive impairment in PAD patients. METHODS: A search strategy encompassing MEDLINE, Scopus, and the Cochrane database was developed to identify peer-reviewed articles examining rates of undiagnosed cognitive impairment in patients with PAD. The following search terms were used: 'PAD'; 'PVD'; 'dementia'; 'peripheral arterial disease'; 'peripheral vascular disease'; 'cognitive impairment'; 'alzheimer's disease' and 'cogniti∗'. Our primary outcome was the incidence of previously undiagnosed cognitive impairment in patients with PAD. RESULTS: The initial search yielded 1492 titles. After removal of duplicates, 961 abstracts were screened to ascertain if they were eligible for inclusion. Abstract review yielded 62 full texts for further evaluation. Eight case-control studies consisting of 1161 patients were included. Analysis of these studies revealed that PAD patients performed significantly worse than controls on a variety of neuropsychological measures. CONCLUSION: Our review indicated that PAD patients are more likely to suffer with undiagnosed cognitive impairment than healthy controls.

Clinical outcomes following open anterior shoulder stabilization for glenohumeral instability in the young collision athlete.

BACKGROUND: Anterior glenohumeral instability occurs most commonly in those aged 15-29, with 72% of individuals younger than 22 years suffering recurrent episodes; collision athletes are at particular risk. In the setting of subcritical glenoid bone loss, arthroscopic Bankart repair is widely used despite concerns of recurrent dislocations when compared with open techniques. Furthermore, indications for bone-block procedures are evolving with the Latarjet procedure being favored amongst recent authors as a primary stabilization method in elite and contact athletes. OBJECTIVE: To determine the efficacy of open modified Bankart stabilization in treating anterior glenohumeral instability in young collision athletes. METHODS: This was a retrospective review of outcomes of consecutive patients aged 15-20 years who underwent unilateral or bilateral open stabilization for recurrent anterior glenohumeral instability over a 7-year period (2007-2015). The cohort was selected as recent literature suggests that this is the group with the highest redislocation rate and poorest outcomes. Outcome assessments included redislocation rate, return to sport, pain score, patient-related satisfaction scores, and the Western Ontario Shoulder Instability Index. RESULTS: A total of 60 patients (55 male: 5 female) of mean age 18 years (range: 15-20 years) were available for follow-up at 7 years. All but 3 were competitive athletes with 18 competing regionally and 9 internationally; rugby union and rugby league represent the most common sports. Fifty-five of 60 (92%) have returned to their desired level of sport with 62% of athletes returning to their previous level of competition sport and 1 retuning at a higher level. The mean postoperative pain score was 2.5/10. The mean time to return to play was 14 months (range: 5-48 months). Eight of 60 shoulders reported redislocation (13%), 7 of these being traumatic dislocations after return to high-impact sporting activities. At 7 years of follow-up, 4 of 60 shoulders (7%) had undergone revision surgery. CONCLUSION: Young collision athletes represent a challenging cohort of instability patients. This study of open modified Bankart in young collision sport athletes revealed excellent outcomes with 92% return to sport and a low revision rate. The results from this cohort rival those of arthroscopic repair. The open procedure described here in this 7-year series represents a robust, reliable technique that could be considered as an alternative to arthroscopic Bankart due to concern for recurrence, while avoiding potential morbidity and complication of bone-block procedures. There is still a role for the open modified Bankart procedure in treating traumatic anterior instability.

Systematic review and meta-analysis of endovascular interventions for Stanford type A aortic dissection.

OBJECTIVE: The standard surgical approach to Stanford type A aortic dissection is open repair. However, up to one in four patients will be declined surgery because of prohibitive risk. Patients who are treated nonoperatively have an unacceptably high mortality. Endovascular repair of the ascending aorta is emerging as an alternative treatment for a select group of patients. The reported rates of technical success, mortality, stroke, and reintervention have varied. The objective of the study was to systematically report outcomes for acute type A dissections repaired using an endovascular approach. METHODS: The systematic review and meta-analysis was conducted in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. We performed online literature database searches through April 2020. The demographic and procedural characteristics of the individual studies were tabulated. Data on technical success, short-term mortality, stroke, and reintervention were extracted and underwent meta-analysis using a random effects model. RESULTS: Fourteen studies with 80 cases of aortic dissection (55 acute and 25 subacute) were included in the final analysis. A wide variation was found in technique and device design across the studies. The outcomes rates were estimated at 17% (95% confidence interval [CI], 10%-26%) for mortality, 15% (95% CI, 8%-23%) for technical failure, 11% (95% CI, 6%-19%) for stroke and 18% (95% CI, 9%-31%) for reintervention. The mean Downs and Black quality assessment score was 13.9 ± 3.2. CONCLUSIONS: The technique for endovascular repair of type A aortic dissection is feasible and reproducible. The results of our meta-analysis demonstrate an acceptable safety profile for inoperable patients who otherwise would have an extremely poor prognosis. Data from clinical trials are required before the technique can be introduced into routine clinical practice.

Validation of ERICVA Risk Score as a Predictor of One Year Amputation-Free Survival of Patients with Critical Limb Ischemia.

BACKGROUND: The ERICVA score was derived to predict amputation-free survival in patients with critical limb ischemia (CLI). It may be a useful tool to stratify patients in trials of novel interventions to treat CLI but, as yet, it has not been externally validated. METHODS: A prospective database of CLI patients was developed during prescreening of patients for a phase 1 stem cell therapy clinical trial. The primary outcome was amputation free survival (AFS) at 1 year. Both the full ERICVA scale (11 parameters) and simplified ERICVA scale (5 parameters) were validated. Data analysis was performed by calculation of the area under the receiver operating characteristic (ROC) curve examining the predictive value of the scores. The Chi-square test was used to examine the association between risk group and one-year AFS and the cumulative survival of the three risk groups was compared using Kaplan Meier survival curves. RESULTS: A series of 179 CLI patients were included in the analysis. The Chi-square test of independence showed a significant association between the risk group (high, medium and low) and one-year AFS outcome (P = 0.0007). Kaplan-Meier survival curve showed significant difference in one-year AFS between the three risk groups (log-rank P < 0.001). The area under the curve (AUC) was found to be 0.63 and 0.61 for the full and simplified score, respectively. The sensitivity of the full score was 0.44 with specificity of 0.84. The simplified score had a sensitivity of 0.28 and specificity of 0.92. CONCLUSION: The ERICVA risk score system was found to have a fair validity but cannot be considered reliable as a single predictor of one year AFS of CLI patients. The simplified score had an AUC almost identical to the full score and can accordingly replace the full score.

Autologous bone marrow mesenchymal stromal cell therapy for "no-option" critical limb ischemia is limited by karyotype abnormalities.

BACKGROUND: Critical limb ischemia (CLI) is the most severe manifestation of peripheral vascular disease. Revascularization is the preferred therapy, but it is not achievable in 25%-40% of patients due to diffuse anatomic distribution of the disease or medical comorbidities. No-option CLI represents an unmet medical need. Mesenchymal stromal cells (MSCs) may provide salvage therapy through their angiogenic and tissue-trophic properties. This article reports a phase 1b clinical study examining the safety and feasibility of intramuscular transplantation of autologous bone-marrow MSCs for patients with no-option CLI. METHODS: Twelve patients were enrolled in the clinical trial, and nine proceeded to bone marrow aspiration and culture expansion of MSCs. RESULTS: A high rate of karyotype abnormality (>30%) was detected in the produced cell batches, resulting in failure of release for clinical administration. Four patients were treated with the investigational medicinal product (IMP), three with a low dose of 20 × 106 MSCs and one with a mid-dose of 40 × 106 MSCs. There were no serious adverse events related to trial interventions, including bone marrow aspiration, IMP injection or therapy. CONCLUSIONS: The results of this trial conclude that an autologous cell therapy approach with MSCs for critical limb ischemia is limited by the high rate of karyotype abnormalities.

Concomitant vs. Staged Treatment of Varicose Tributaries as an Adjunct to Endovenous Ablation: A Systematic Review and Meta-Analysis.

OBJECTIVE: This review compares the outcomes of both concomitant and staged superficial varicose tributary (SVT) interventions as an adjunct to endovenous truncal ablation. METHODS: A systematic search of Medline through Pubmed, Embase, and the Cochrane Central Register of Controlled Trials was last performed in November 2019. All studies comparing the outcomes of both concomitant and staged treatments for SVT as an adjunct to endovenous truncal ablation were included. Each included study was subject to an evaluation of methodological quality using the Downs and Black assessment tool. Outcomes assessed included rates of re-intervention, complications, and thrombotic events. Quality of life (QOL) and disease severity were also analysed. Data were pooled with a random effects model. RESULTS: Fifteen studies (6 915 limbs) were included for analysis. Included studies were of reasonable methodological quality. Re-intervention rates were significantly lower in the concomitant group (6.3% vs. 36.1%) when compared with staged intervention (relative risk [RR] 0.21 [95% CI 0.07-0.62], p = .004, I2 = 90%, p ≤ .001). Reported complications (RR 1.14 [95% CI 0.67-1.93], p = .64) and rates of deep venous thrombosis (RR 1.41 [95% CI 0.72-2.77] p = .31) were similar in each group. Overall disease severity (Venous Clinical Severity Score) was lower in the concomitant group (-1.16 [95% CI, -1.97- -0.35] p = .005), while QOL, assessed using the Aberdeen Varicose Vein Questionnaire, favoured concomitant treatment when measured at less than three months (weighted mean difference [WMD] -3.6 [95% CI, -7.17- -0.03] p = .050) and between three and 12 months (WMD -1.61 [95% CI, -2.99- -0.23] p = .020). CONCLUSION: Concomitant and staged treatments are safe and effective. Improvements in early disease severity and QOL scores were better in the concomitant group. While meta-analysis suggests that concomitant intervention offers significantly lower rates of re-intervention, studies assessing its merits are subject to some biases. This benefit was not reflected by the randomised trial subgroup analysis, which identified no difference in re-intervention.

Outcomes of a 2-Portal Endoscopic Technique for Osseous Lesions Resulting in Posterior Ankle Impingement Syndrome.

Posterior ankle impingement syndrome is common in sporting populations and encompasses a range of disorders that cause posterior ankle pain during maximal forced plantarflexion. The aim of this study was to evaluate the short- and medium- to long-term outcomes of 2-portal endoscopic surgery for osseous lesions causing posterior ankle impingement syndrome. This was a retrospective case series analysis of all patients who underwent 2-portal endoscopic surgery at a single institution between 2005 and 2016. Visual analogue scales and selected components of the Short Form of the Revised Foot Function Index were used to assess ankle function, with the median follow-up time being 4.8 years. Of the 52 patients, 49 (94%) were able to return to their previous sport/physical activity, with the mean time taken being 5.8 months. At the completion of follow-up, the mean pain score during exercise had improved from 7.5 to 0.9 points. The mean work and sporting function scores also improved, from 5.9 to 9.6 points and 2.9 to 8.8 points, respectively. The mean score of the Short Form of the Revised Foot Function Index also improved by 77.7 points, from 84.4 to 6.7 at the completion of follow-up. There were no postoperative infections or any other major complications. This study provides strong supporting evidence for the use of hindfoot endoscopy in the treatment of posterior ankle impingement syndrome in athletes.

Effects of Ischemic Preconditioning on Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis.

BACKGROUND: Ischemic preconditioning is an innate mechanism of cytoprotection against ischemia, with potential for end-organ protection. The primary goal of this study was to systematically review the literature to determine the effect of ischemic preconditioning on outcomes after open and endovascular abdominal aortic aneurysm (AAA) repair. METHODS: The methodology followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We included randomized clinical trials that evaluated the effect of remote ischemic preconditioning (RIPC) in reducing morbidity and mortality in patients undergoing open or endovascular AAA repair surgery. The primary outcomes were death, myocardial infarction, and renal impairment. Outcomes were addressed separately for open AAA repair and endovascular AAA repair (EVAR). Data were collected on patient characteristics, methodology, and preconditioning protocol for each trial. RESULTS: Nine trials of ischemic preconditioning in aortic aneurysm surgery were included with a total of 599 patients; 336 patients were included in the open AAA repair meta-analysis, and 263 patients were included in the EVAR meta-analysis. For both open and endovascular repairs, ischemic preconditioning did not have a significant effect on death, myocardial infarction, or renal impairment requiring dialysis. CONCLUSIONS: The randomized clinical trials investigating the effect of ischemic preconditioning on outcomes after open and endovascular AAA repair that have been completed to date have not been adequately powered to evaluate improvements in patient-important outcomes. The evidence is insufficient to support the use of ischemic preconditioning for AAA repair in clinical practice. The variability in treatment effect across studies may be explained by clinical and methodological heterogeneity.

Remote Ischemic Pre-conditioning in the Management of Intermittent Claudication: A Pilot Randomized Controlled Trial.

BACKGROUND: Animal data suggest that remote ischemic conditioning (RIC) can improve blood flow in ischemic limbs and, consequently, may benefit claudication patients. Supervised exercise is the preferred first-line intervention for patients with intermittent claudication (IC) but is constrained by limited availability and logistical issues, particularly in rural settings. The aim of this study is to evaluate remote ischemic pre-conditioning in the management of intermittent claudication patients. METHODS: We undertook a randomized clinical trial to evaluate RIC's effect in claudication patients. Stable IC patients were randomly allocated to receive RIC alone, structured exercise (SE) alone, RIC plus SE, or to a control group which received standard advice and risk factor modification. Patients received their intervention over a 28-day period. RIC patients attended an RIC clinic every 3-4 days to undergo 4 cycles of 5-min upper limb ischemia followed by 5-min reperfusion induced with a standard blood pressure cuff. RESULTS: Forty-five patients were randomized, of whom 40 completed the trial (10 patients per group). The RIC alone, SE alone, and RIC plus SE groups all demonstrated significant improvements in pain-free walking distance and ankle-brachial pressure indices at 30 days. There were no differences in the magnitude of improvements between the groups. CONCLUSIONS: Compared with standard care RIC is promising as a home-delivered intervention. It appears to be equivalent to SE in the treatment of IC, with no apparent additive benefit to combining the 2 interventions in this small size sample. Large-scale randomized controlled trial is needed for validation.