Comparison of revascularization and conservative treatment for hemorrhagic moyamoya disease in East Asian Countries: a single-center case series and a systematic review with meta-analysis
Frontiers in neurology. 2023;14:1169440
OBJECTIVE The optimal treatment approach for hemorrhagic moyamoya disease (HMMD) remains a topic of debate, particularly regarding the comparative efficacy of revascularization versus conservative treatment. Our study, which included a single-center case series and a systematic review with meta-analysis, aimed to determine whether surgical revascularization is associated with a significant reduction in postoperative rebleeding, ischemic events, and mortality compared to conservative treatment among East Asian HMMD patients. METHODS We conducted a systematic literature review by searching PubMed, Google Scholar, Wanfang Med Online (WMO), and the China National Knowledge Infrastructure (CNKI). The outcomes of surgical revascularization and conservative treatment, including rebleeding, ischemic events and mortality, were compared. The authors' institutional series of 24 patients were also included and reviewed in the analysis. RESULTS A total of 19 East Asian studies involving 1,571 patients as well as our institution's retrospective study of 24 patients were included in the study. In the adult patients-only studies, those who underwent revascularization had significantly lower rates of rebleeding, ischemic events, and mortality compared to those who received conservative treatment (13.1% (46/352) vs. 32.4% (82/253), P < 0.00001; 4.0% (5/124) vs. 14.9% (18/121), P = 0.007; and 3.3% (5/153) vs. 12.6% (12/95), P = 0.01, respectively). In the adult/pediatric patients' studies, similar statistical results of rebleeding, ischemic events, and mortality have been obtained (70/588 (11.9%) vs. 103/402 (25.6%), P = 0.003 or <0.0001 in a random or fixed-effects model, respectively; 14/296 (4.7%) vs. 26/183 (14.2%), P = 0.001; and 4.6% (15/328) vs. 18.7% (23/123), P = 0.0001, respectively). CONCLUSION The current single-center case series and systematic review with meta-analysis of studies demonstrated that surgical revascularization, including direct, indirect, and a combination of both, significantly reduces rebleeding, ischemic events, and mortality in HMMD patients in the East Asia region. More well-designed studies are warranted to further confirm these findings.
Optimal Hemostatic Band Duration After Transradial Angiography or Intervention: Insights From a Mixed Treatment Comparison Meta-Analysis of Randomized Trials
Circulation. Cardiovascular Interventions. 2023;16(2):e012781
BACKGROUND The optimal duration of hemostatic compression post transradial access is controversial. Longer duration increases the risk of radial artery occlusion (RAO) while shorter duration increases the risk of access site bleeding or hematoma. As such, a target of 2 hours is typically used. Whether a shorter or longer duration is better is not known. METHODS A PubMed, EMBASE, and clinicaltrials.gov databases were searched for randomized clinical trials of different duration (<90 minutes, 90 minutes, 2 hours, and 2-4 hours) of hemostasis banding. The efficacy outcome was RAO, primary safety outcome was access site hematoma, and secondary safety outcome was access site rebleeding. Primary analysis compared the effect of various duration in reference to the 2 hours duration using a mixed treatment comparison meta-analysis. RESULTS Of the 10 randomized clinical trials included with 4911 patients, when compared to the 2-hour reference duration, there was a significantly higher risk of access site hematoma with 90 minutes (odds ratio, 2.39 [95% CI, 1.40-4.06]) and <90 minutes (odds ratio, 3.61 [95% CI, 1.79-7.29]) but not with the 2 to 4 hours duration. When compared with the 2-hour reference, there was no significant difference in access site rebleeding or RAO with shorter or longer duration but the point estimates favored longer duration for access site rebleeding and shorter duration for RAO. Duration of <90 minutes and 90 minutes ranked 1 and duration of 2 hours ranked 2 as the most efficacious duration whereas duration of 2 hours ranked 1 and 2 to 4 hours ranked 2 as the safest duration. CONCLUSIONS In patients undergoing transradial access for coronary angiography or intervention, a hemostasis duration of 2 hours offers the best balance for efficacy (prevention of RAO) and safety (prevention of access site hematoma/rebleeding).
Bleeding Episodes in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Undergoing Very Early Versus Standard Care Invasive Examination (from the Very EaRly vs Deferred Invasive Evaluation Using Computerised Tomography [VERDICT] Trial)
The American journal of cardiology. 2022
Bleeding is known to influence the prognosis in patients with acute coronary syndromes. In this predefined secondary outcome analysis of the Very EaRly vs Deferred Invasive evaluation using Computerized Tomography (VERDICT) trial, we investigated whether a very early invasive coronary angiography (ICA), compared with one performed within 48 to 72 hours (standard care), was associated with fewer serious bleedings. Furthermore, we tested the association between demographic data including GRACE score and serious bleedings as well as bleedings and mortality. In the 2,147 patients included in the main study, bleedings within 30 days of admission were assessed based on Thrombolysis In Myocardial Infarction and Bleeding Academic Research Consortium criteria. Differences were calculated by cumulative incidence methods and Grays test. Variables associated with bleeding and mortality were estimated by Cox proportional hazard models. Serious (Bleeding Academic Research Consortium 3abc) bleeding rates were low (15 [1.4%, standard] vs 12 [1.2%, early], p = 0.56). There were no fatal bleedings or serious bleedings before ICA in either group. By multivariate analysis, there was no difference in bleedings between the 2 groups. Female gender (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.2 to 6.4; p = 0.02), anemia (HR 7.0, 95% CI 2.8 to 17.0; p <0.001), and increasing blood pressure (HR 1.3, 95% CI 1.1 to 1.5; p = 0.01) were individually associated with serious bleeding, whereas GRACE score >140 was not (HR 1.03, 95% CI 0.4 to 2.9; p = 0.96). In conclusion, serious bleedings were few, and there were none before ICA in either group. A very early invasive strategy did not reduce serious bleedings within 30 days, which was associated with female gender, increasing blood pressure, and anemia.
Autologous Cultured Bone Marrow-Derived Mesenchymal Stem Cells in a Fibrin Spray to Treat Venous Ulcers: A Randomized Controlled Double-Blind Pilot Study
Surgical technology international. 2022;40
We treated a small cohort of venous ulcers that were very unresponsive to standard and advanced therapies with autologous cultured bone marrow-derived mesenchymal stem cells (MSCs). This pilot clinical trial was randomized, controlled, and double-blinded. Subjects were treated with either normal saline (Group A), fibrin spray alone (Group B), or MSCs in fibrin (1 million cells/cm2 of wound bed surface) (Group C). The control and test materials were applied to the wound using a double-barreled syringe with thrombin and fibrinogen (with or without MSCs) in each barrel, or saline alone in both barrels. The MSCs were separated, cultured in vitro, and expanded in a dedicated Good Manufacturing Practice (GMP) facility from 30-50 ml of bone marrow aspirate obtained from the iliac crest in Group C subjects. To ensure that the study remained controlled and blinded, subjects who were randomized to one of the two control arms (saline or fibrin) underwent sham bone marrow aspiration performed by a hematologist who anesthetized the iliac crest area down to and pushing against the periosteum, but without penetrating the bone marrow. Therefore, both the clinician who evaluated wound progress and the study subjects had no knowledge of whether bone aspiration was actually performed and what treatment had been applied to the wound. The study was performed after full FDA investigational new drug (IND) approval. The primary endpoint was the rate of healing (wound closure as linear healing from the wound margins in cm/week), as measured by the Gilman equation. One-way ANOVA was used to calculate the statistical significance of differences between the mean healing rates of each of the 3 treatment groups every 4 weeks and over the 24 weeks of treatment. Overall, treatment with MSCs accelerated the healing rate by about 10-fold compared to those in the saline and fibrin control groups. Although the total number of patients in this pilot study was small (n=11), the statistical significance was surprisingly promising: p<0.01 and f-ratio of 15.9358. No serious adverse events were noted. This small but carefully performed prospective, controlled, randomized, and double-blinded pilot study in a rare population of totally unresponsive patients adds to previous reports showing the promise of MSCs in the treatment of chronic wounds and provides proof of principle for how to approach this type of very demanding clinical and translational research.
Carvedilol versus endoscopic band ligation for secondary prophylaxis of variceal bleeding-Long-term follow-up of a randomised control trial
Alimentary pharmacology & therapeutics. 2022
BACKGROUND AND AIMS Carvedilol reduces rates of variceal bleeding and rebleeding by lowering portal pressure. However, an associated pleiotropic survival benefit has been proposed. We aimed to assess long-term survival in a cohort of patients previously randomised to receive either carvedilol or endoscopic band ligation (EBL) following oesophageal variceal bleeding (OVB). METHODS The index study randomised 64 cirrhotic patients with OVB between 2006 and 2011 to receive either carvedilol or EBL. Follow-up was undertaken to April 2020 by review of electronic patient records. The primary outcome was survival. Other outcomes including variceal rebleeding and liver decompensation events were compared. RESULTS 26 out of 33 participants received carvedilol in the follow-up period and 28 out of 31 attended regular EBL sessions. The median number of follow-up days for all patients recruited was 1459 (SE = 281.74). On the intention to treat analysis, there was a trend towards improved survival in the carvedilol group (p = 0.09). On per-protocol analysis, carvedilol use was associated with improved long-term survival (p = 0.005, HR 3.083, 95% CI 1.397-6.809), fewer liver-related deaths (0% vs 22.57%, p = 0.013, OR ∞, 95%CI 1.565-∞) and fewer admissions with decompensated liver disease (12% vs 64.29%, p = 0.0002, OR 13.2, 95% CI 3.026-47.23) compared to the EBL group. There was no statistically significant difference in variceal rebleeding rates. CONCLUSION Following OVB in cirrhotic patients, carvedilol use is associated with survival benefit, fewer liver-related deaths and fewer hospital admissions with decompensated liver disease. Further studies are needed to validate this finding.
Safety and Efficacy of Thrombin for Bleeding Gastric Varices: A Systematic Review and Meta-Analysis
Digestive diseases and sciences. 2021
INTRODUCTION The optimal therapy for bleeding-related gastric varices is still a controversial topic. There is a paucity of literature that comprehensively summarizes the available literature regarding safety and efficacy of thrombin in bleeding gastric varices. METHODS Four independent reviewers performed a comprehensive review of all original articles published from inception to October 2020, describing the use of thrombin for management of bleeding gastric varices. Primary outcomes were (1) pooled early and late rebleeding rate, (2) pooled gastric variceal related mortality rate, (3) pooled rescue therapy rate, and (4) pooled adverse event rate with the use of thrombin in bleeding gastric varices. The meta-analysis was performed and the statistics were two-tailed. Finally, probability of publication bias was assessed using funnel plots and with Egger's test. RESULTS Eleven studies were included in the analysis after comprehensive search. This yielded a pooled early rebleeding rate of 9.3% (95% CI 4.9-17) and late rebleeding rate 13.8% (95% CI 9-20.4). Pooled rescue therapy rate after injecting thrombin in bleeding gastric varices was 10.1% (95% CI 6.1-16.3). The pooled 6-week gastric variceal-related mortality rate after injecting thrombin in bleeding gastric varices was 7.6% (95% CI 4.5-12.5). There were a total of four adverse events out of a total of 222 patients with pooled adverse event rate after injecting thrombin in bleeding gastric varices was 5.6% (95% CI 2.9-10.6). CONCLUSION In summary, the systematic review and meta-analysis on the use of thrombin for bleeding gastric varices suggest low rates of rebleeding and minimal rates of adverse events. While, early and late rebleeding rate and rescue therapy rate are similar to cyanoacrylate-based therapy, the minimal rates of adverse events are perhaps the most important benefit of thrombin. Thus, the current data suggest that thrombin is a very promising therapeutic alternative with low risk of adverse events for bleeding gastric varices.
Primary and Secondary Prevention Strategies for Gastrointestinal Bleeding in Patients with Left Ventricular Assist Device: A Systematic Review and Network Meta-analysis
Current problems in cardiology. 2021;:100835
Recurrent gastrointestinal bleeding (GIB) is a common complication following left ventricular assist device (LVAD) implantation. Our study aimed to estimate the comparative efficacy of different pharmacologic interventions for the prevention of GIB, through a network meta-analysis (NMA). A total of 13 observational studies comparing six strategies. Among those, 4 were for primary, and 9 were for secondary prevention of GIB. On NMA, thalidomide (Hazard ratio [HR]: 0.016, Credible interval [CrI]I: 0.00053-0.12), omega-3-fatty acid (HR:0.088, CrI: 0.026-0.77), octreotide (HR: 0.17, CrI: 0.0589-0.41) and danazol (HR:0.17, CrI: 0.059-0.41) reduced the risk of GIB. The use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blocker (ACEi/ARB) and digoxin were not associated with any significant reduction. Based on NMA, combining indirect treatment comparisons, thalidomide, danazol, and octreotide treatments were associated with decreased risk of recurrent GIB. Additionally, Omega 3 fatty acids were associated with a lower risk of the primary episode of GIB in the LVAD patient population.
The effect of platelet-rich plasma-fibrin glue dressing in combination with oral vitamin E and C for treatment of non-healing diabetic foot ulcers: A randomized, double-blind, parallel-group, clinical trial
Expert opinion on biological therapy. 2021
OBJECTIVE The current study assesses the effects of platelet-rich plasma-fibrin glue (PRP-FG) dressing along with oral vitamin E and C on wound healing and biochemical markers in patients with non-healing diabetic foot ulcers (non-healing DFU). METHODS This randomized, double-blind, placebo-controlled trial was performed on twenty-five patients with non-healing DFU. Patients were treated with PRP-FG dressing plus oral vitamin E and C (intervention group) or PRP-FG dressing plus placebo (control group) for eight weeks. RESULTS Eight weeks after treatment, six wounds in the intervention group and two wounds in the control group were completely closed, and also wound size significantly reduced in both intervention (-9.7 ± 6.9 cm(2), p = 0.002), and control (-5.6 ± 5.4 cm(2), p = 0.003) groups. This reduction in wound size was significantly greater in the intervention group compared to the control group (p = 0.019). Also, a significant decrease in prooxidant-antioxidant balance (PAB) index, ESR, and hs-CRP were observed in the intervention group compared to the control group (p < 0.05). CONCLUSION Results of this trial showed that PRP-FG dressing along with oral vitamin E and C could be used to increase wound healing in patients with non-healing DFU by enhancing the wound healing process and reducing oxidative stress. TRIAL REGISTRATION This trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04315909).
Dissolvable intranasal haemostatic agents for acute epistaxis: a systematic review and meta-analysis
Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery. 2021
INTRODUCTION Nasal packing is the mainstay of epistaxis management; however, packs cause patient discomfort and can lead to hospital admission. Absorbable haemostats provide clotting factors or act as a substrate to stimulate clotting and represent a potential treatment alternative. A systematic review was performed to evaluate the efficacy of topical haemostats in the management of epistaxis. METHODS A systematic literature search of 7 databases was performed. Only eligible randomised controlled-trials (RCTs) and observational studies were included. The primary outcome was short-term haemostatic success (<7 days). Secondary outcomes included long-term haemostatic control (no re-bleeding 7-30 days), patient discomfort and adverse effects. Meta-analysis was performed where possible. RESULTS Of 2,249 records identified, 12 were included in the qualitative synthesis and 4 RCTs were included in meta-analysis. The following haemostats were reported: gelatin-thrombin matrix (n=8), aerosolised/gel tranexamic acid (n=1), cellulose agents (n=2), and fibrin sealants (n=1). Studies involving tranexamic acid on removable delivery devices (e.g. pledgets) were excluded. There was heterogeneity in outcome measures and inclusion criteria (coagulopathies/anticoagulants were excluded in 3 RCTs and 2 observational studies). The short-term haemostatic success varied between studies (13.9% to 100%). No significant post-procedural complications were reported. The meta-analysis favoured absorbable haemostatic agent versus packing (risk ratio 1.20; 95% confidence interval 1.05 to 1.37; p=0.007). The risk of bias across all studies was moderate to high. CONCLUSIONS The evidence suggests haemostatic agents are effective at managing acute epistaxis when compared with nasal packing. More data are required before recommendations can be made regarding management in patients on anticoagulants.
Two HEmostasis Methods After TransradIal Catheterization: THEMATIC Randomized Clinical Trial
The Journal of cardiovascular nursing. 2020
OBJECTIVE The aim of this study was to compare the effect of 2 hemostasis devices on the incidence of radial artery occlusion (RAO) after transradial cardiac catheterization. BACKGROUND Radial artery occlusion is the most prevalent ischemic complication after radial artery catheterization. There is still no predictive pattern of vessel patency assessment, and the comparative effectiveness of different hemostasis techniques has yet to be established. METHODS This study used a randomized clinical trial of adult patients undergoing transradial cardiac catheterization. Participants were randomized into an intervention group (hemostasis with the TR Band device) and a control group (hemostasis with a conventional pressure dressing). The primary end point was the incidence of RAO (at discharge and at 30 days post catheterization). RESULTS Among the 600 patients included (301 in the intervention group and 299 controls), immediate RAO occurred in 24 (8%) in the TR Band group and 19 (6%) in the pressure-dressing group; at 30 days, RAO was present in 5 patients (5%) in the TR Band group and 7 (6%) in the pressure-dressing group. On multivariate analysis, peripheral vascular disease was the only independent predictor of RAO at discharge and at 30 days. CONCLUSIONS The incidence of RAO was similar in patients who received hemostasis with a TR Band versus a pressure dressing after transradial cardiac catheterization.