Feasibility and safety values of activated clotting time-guided systemic heparinization in coil embolization for unruptured intracranial aneurysms.

OBJECTIVE: This study aimed to evaluate the feasibility and safety values of activated clotting time (ACT)-guided systemic heparinization in reducing periprocedural thrombosis and bleeding complications during coil embolization of unruptured intracranial aneurysms. METHODS: A total of 228 procedures performed on 213 patients between 2016 and 2021 were included in the retrospective analysis. The target ACT was set at 250 s. Logistic regression was performed to assess predictors for the occurrence of thrombosis and bleeding. Receiver operating characteristic (ROC) analyses were employed to determine the optimal cut-off values for ACT, heparinization, and procedure time. RESULTS: Most (85.1%) of procedures were stent-assisted embolization. The mean baseline ACT was 128.8 ± 45.7 s. The mean ACT at 20 min after the initial intravenous heparin loading of 78.2 ± 18.8 IU/kg was 185 ± 46.4 s. The mean peak ACT was 255.6 ± 63.8 s with 51.3% (117 cases) achieving the target ACT level. Peak ACT was associated with symptomatic thrombosis (OR per second, 1.008; 95% CI, 1.000-1.016; P = 0.035) (cut-off value, 275 s; area under ROC (AUROC), 0.7624). Total administered heparin dose per body weight was negatively associated with symptomatic thrombosis (OR per IU/kg, 0.972; 95% CI, 0.949-0995; P = 0.018) (cut-off value, 294 IU/kg; AUROC, 0.7426) but positively associated with significant bleeding (OR, 1.008 per IU/kg; 95% CI, 1.005-1.012; P <0 .001) (cut-off value, 242 IU/kg; AUROC, 0.7391). Procedure time was significantly associated with symptomatic thrombosis (OR per minute, 1.05; 95% CI, 1.017-1.084; P value = 0.002) (cut-off value, 158 min; area under ROC, 0.8338). CONCLUSION: This study demonstrated that ACT-guided systemic heparinization was feasible to achieve the target ACT value and proposes probable safety thresholds to prevent periprocedural complications through reducing procedure time during coil embolization of unruptured intracranial aneurysms in the stent era.

Wasp-stung rat model translationally expresses the coagulopathy manifestations of human wasp patients.

Two over 80 wasp stings male victims appeared severe abnormal coagulation were consecutively examined by thromboelastography (TEG) guided with heparinase during hospitalization. However, the cause of coagulopathy remains unsolved. Rats were applied to establish a wasp-stung animal model highly resembled the manifestations of wasp-stung patients. According body surface area conversion, Sprague-Dawley rats were stung based on wasp sting numbers (0, 4, 8, 12 stings; n = 6 each) with various exposure times (0, 1, 3, 6 h) to determine the simulation of coagulopathy. The blood R, K values, and angle degree of wasp-stung rats were measured by TEG. The TEG profiles of stung rats were found to be concomitant with that of wasp-stung patients. Data showed that the endogenous heparinization of rats was time-dependent. Compared to the TEG profile of eight stings given rat, the coagulation time of 2 mm clot formation at 3 h (R value) was longer than that at 0 h. The coagulation time was prolonged with increasing sting numbers when compared to the various stings at 1, 3, and 6 h exposed. Interestingly, there was observed the peak coagulation at 3 h of eight stings. The Ck-standard and Ck-heparinase at 3 h after 8 stings given were R: 9.6-4.4 min; K: 3.8-1.8 min; angle degree: 49.8-68.0, respectively. The original data of R, K values and angle degree in two wasp-stung victims were 11.7-13.6 min, 4.3-5.5 min, and 41.2-32.8° in CK-standard, respectively; whereas those of the CK-heparinase groups were 5.6-6.7 min, 2.4-2.5 min, and 59.5-58.8°, correspondingly. Conclusively, this massive wasp-stung animal model can be applied to the investigations of pathogenesis and provides a clinical strategy or guideline for clinical intervention.

Surface Heparinization of a Magnesium-Based Alloy: A Comparison Study of Aminopropyltriethoxysilane (APTES) and Polyamidoamine (PAMAM) Dendrimers.

Magnesium (Mg)-based alloys are biodegradable metallic biomaterials that show promise in minimizing the risks of permanent metallic implants. However, their clinical applications are restricted due to their rapid in vivo degradation and low surface hemocompatibilities. Surface modifications are critically important for controlling the corrosion rates of Mg-based alloys and improving their hemocompatibilities. In the present study, two heparinization methods were developed to simultaneously increase the corrosion resistance and hemocompatibility of the AZ31 Mg alloy. In the first method, the surface of the AZ31 alloy was modified by alkali-heat treatment and then aminolyzed by 3-amino propyltriethoxy silane (APTES), a self-assembly molecule, and heparin was grafted onto the aminolyzed surface. In the second method, before heparinization, polyamidoamine dendrimers (PAMAM4-4) were grafted onto the aminolyzed surface with APTES to increase the number of surface functional groups, and heparinization was subsequently performed. The presence of a peak with a wavelength of about 1560 cm-1 in the FTIR spectrum for the sample modified with APTES and dendrimers indicated aminolysis of the surface. The results indicated that the corrosion resistance of the Mg alloy was significantly improved as a result of the formation of a passive layer following the alkali-heat treatment. The results obtained from a potentiodynamic polarization (PDP) test showed that the corrosion current in the uncoated sample decreased from 25 µA to 3.7 µA in the alkali-heat-treated sample. The corrosion current density was reduced by 14 and 50 times in samples treated with the self-assembly molecules, APTES and dendrimers, respectively. After heparinization, the clotting time for pristine Mg was greatly improved. Clotting time increased from 480 s for the pristine Mg sample to 630 s for the APTES- and heparin-modified samples and to 715 s for the PAMAM- and heparin-modified samples. Cell culture data showed a slight improvement in the cell-supporting behavior of the modified samples.

Survival of a patient who received extracorporeal membrane oxygenation due to postoperative myocardial infarction: A case report.

BACKGROUND: Cardiac arrest after noncardiac surgery is a dangerous complication that may contribute to mortality. Because of the high mortality rate and many complications of cardiac arrest, it is very important to identify and correct a reversible etiology early. By reporting the treatment process of this case, we aimed to broaden the diagnosis and treatment of cardiac arrest after noncardiac surgery and describe how cardiopulmonary resuscitation using extracorporeal membrane oxygenation (ECMO) can improve a patient's chance of survival. CASE SUMMARY: A 69-year-old man visited our hospital complaining of low back pain on July 12, 2021. Magnetic resonance imaging showed lumbar disc herniation. Two hours after lumbar disc herniation surgery, the patient developed cardiac arrest. Cardiopulmonary resuscitation was performed, and ECMO was started 60 min after the initiation of cardiopulmonary resuscitation. Regarding the etiology of early cardiac arrest after surgery, acute myocardial infarction and pulmonary embolism were considered first. Based on ultrasound evaluation, acute myocardial infarction appeared more likely. Coronary angiography confirmed occlusion of the left anterior descending branch, and coronary artery stenting was performed. Pulmonary artery angiography was performed to exclude pulmonary embolism. Due to heparinization during ECMO and coronary angiography, there was a large amount of oozing blood in the surgical incision. Therefore, heparin-free ECMO was performed in the early stage, and routine heparinized ECMO was performed after hemorrhage stabilization. Eventually, the patient was discharged and made a full neurologic recovery. CONCLUSION: For early postoperative cardiac arrest, acute myocardial infarction should be considered first, and heparin should be used with caution.

Hemostatic complications and systemic heparinization in pediatric post-cardiotomy veno-arterial extracorporeal membrane oxygenation failed to wean from cardiopulmonary bypass.

Background: Hemostatic complications and the need for large amounts of blood products are major obstacles during veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Additionally, the occurrence of coagulopathy after cardiopulmonary bypass (CPB) affects systemic heparinization in pediatric post-cardiotomy patients. This study compares hemostatic complications in pediatric post-cardiotomy VA-ECMO patients for failure to wean from CPB with those who received post-cardiotomy VA-ECMO for other indications, while also exploring the relationship between different stages-hemostatic complications and the timing of systemic heparinization. Methods: We retrospectively analyzed 146 pediatric patients who received post-cardiotomy VA-ECMO support (CPB-ECMO, n=96 vs. non-CPB-ECMO, n=50) from January 2005 to June 2020. Patients were divided into survivors (n=46) and non-survivors (n=50) according to in-hospital mortality in the CPB-ECMO group. We compared clinical outcomes between the groups, then examined the associations between the timing of systemic heparinization after ECMO implantation and different stages-hemostatic complications, in the CPB-ECMO group. Results: We found that the risk of early bleeding was significantly increased in patients who failed to wean from CPB. The presence of early bleeding was accompanied by the higher demand for blood products transfusion in the CPB-ECMO group, and for treatment the patients received a longer delayed continuous heparin infusion. As a result of using delayed systemic heparinization to avoid early bleeding, early hemolysis increased in the CPB-ECMO group. A delayed systemic heparinization of 9.5 hours showed the best Youden index results and the overall greatest accuracy in predicting early hemolysis. Conclusions: A direct transition from CPB to ECMO in pediatric post-cardiotomy patients significantly increases early bleeding. Delayed systemic heparinization to reduce early bleeding has good discrimination for predicting early hemolysis in the CPB-ECMO group. Coagulopathy is complex in pediatric post-cardiotomy VA-ECMO patients who failed to wean from CPB, and, as such, it is extremely important to monitor coagulation-related indicators in multiple dimensions to determine the timing of systemic heparinization.

Diffusion-weighted imaging-positive lesions following endovascular treatment for ruptured and unruptured aneurysms: Its incidence according to antithrombotic drugs.

OBJECTIVE: Microembolic infarcts are frequently observed on diffusion-weighted imaging (DWI) following endovascular treatment. We investigated DWI-positive lesions and symptomatic ischemic complications (SICs) in patients with ruptured and unruptured aneurysms following coiling and the relationship between DWI-positive lesions and antithrombotic drugs. METHODS: Between January 2016 and December 2020, 83 patients underwent DWI within 48 h following endovascular treatment for ruptured (n=30) and unruptured (n=53) aneurysms. RESULTS: The overall rate of DWI-positive lesions was 55.4%. There were no significant differences in the occurrence rate (45.3% vs. 43.3%, p=1.000) and the number of lesions (2.7±4.6 vs. 4.0±5.3, p=0.237) between unruptured and ruptured aneurysms. SIC occurred more frequently in patients with ruptured aneurysms than unruptured ones (20.0% vs. 1.9%, p=0.015). The cutoff value of DWI-positive lesions for predicting SIC was 5 (sensitivity 100%, specificity 78.9%). The procedure time was significantly longer in patients with DWI-positive lesions ≥5 than those with DWI-positive lesions <5 (104.1±43.8 vs. 85.1±30.8 min, p=0.030). Patients with DWI-positive lesions <5 were more frequently observed in the postprocedural heparinization group than in the no heparinization group (85.7% vs. 58.5%, p=0.012). CONCLUSIONS: The incidence of DWI-positive lesions did not differ significantly between the ruptured and unruptured aneurysms. However, SIC occurred more frequently in patients with ruptured aneurysms. Longer procedure time is a risk factor for DWI-positive lesions, and postprocedural heparinization seems to reduce the incidence of DWI-positive lesions.

Endovascular mechanical thrombectomy for cerebral venous sinus thrombosis after mRNA-based SIRS-CoV-2 vaccination.

Background: As vaccinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue worldwide, increased rates of venous thrombotic events, mainly as cerebral venous sinus thrombosis (CVST), have been reported following adenovirus vector-based SARS-CoV-2 vaccination. However, few reports have described the occurrence of venous thrombosis after messenger RNA (mRNA)-based vaccination. Here, we describe a case of CVST after a first dose of mRNA-based vaccination that was treated with emergent endovascular mechanical thrombectomy and systemic heparinization.Case Description.A 43-year-old, previously healthy man suffered severe headache and partial seizures affecting the left arm 4 days after receiving the first dose of an mRNA-based SARS-CoV-2 vaccination (FC3661; Pfizer/BioNTech). Computed tomography showed intraparenchymal hemorrhage. Seven days after vaccination, symptoms worsened and he was transferred to our tertiary hospital. Magnetic resonance venography revealed CVST with occlusion of the superior sagittal sinus (SSS) and right transverse sinus (TS). Since no findings suggested thrombosis with thrombocytopenia syndrome, the patient underwent systemic heparinization and emergent mechanical thrombectomy with balloon transluminal angioplasty, a stent retriever and an aspiration catheter. Complete SSS and right TS recanalization were achieved and the patient was discharged without neurological deficits. Conclusion: Clinicians should be aware that apparently healthy individuals with no risk factors can develop CVST after receiving an mRNA-based vaccine and appropriate treatment including EMT need to be performed immediately.(228 words).

A case with no administration of protamine to neutralize heparin in aortic valve replacement with cardiopulmonary bypass.

Systemic heparinization is necessary before cardiopulmonary bypass (CPB) in cardiac surgery, and protamine administration to neutralize heparin for hemostasis is required at the end of CPB. Because protamine is an allogeneic protein extracted from the sperm of specific fish, serious adverse reactions can occur during clinical application, with potentially catastrophic outcomes. A male patient received aortic valve replacement with CPB. Severe allergic reactions occurred postoperatively after protamine administration for neutralization. Emergency heparinization and CPB re-establishment were conducted with no further hemostatic treatment with protamine. However, the patient suffered a massive hemorrhage and was treated symptomatically with blood transfusion and rehydration. Following two thoracotomies for hemostasis, the patient healed and was eventually discharged. Protamine is irreplaceable as the only hemostatic that neutralizes heparin for cardiac CPB at present. However, because it is an alloprotein, it can cause serious allergic reactions after entering the human body, and caution should be exercised during the process of its clinical application.

Pulmonary artery reconstruction for non-small cell lung cancer: Surgical management and long-term outcomes.

OBJECTIVE: Pulmonary artery (PA) reconstruction is performed to avoid pneumonectomy for non-small cell lung cancer (NSCLC). Our objective was to assess the safety and efficacy of performing PA reconstruction without systemic heparinization during resections of NSCLC. METHODS: Among 3537 patients with resected NSCLC between 2008 and 2019, 130 (3.7%) patients underwent PA reconstruction to avoid pneumonectomy without intraoperative systemic heparinization. We investigated surgical outcome. The median follow-up time was 37 months. RESULTS: As to PA reconstruction, tangential suture, patch closure (autologous pericardium), end-to-end anastomosis, and conduit were performed in 56, 26, 32, and 16 patients (autologous pericardium, 13; resected pulmonary vein, 3), respectively. Combined bronchial sleeve resection was performed in 68 (52%) patients. The mean operative time was 261 minutes. The procedure-related complications were 2 PA thromboses with pericardial conduit requiring completion pneumonectomy and 2 massive hemoptysis of a bronchopulmonary fistula leading to death (operative mortality, 1.5%). PA bending and mechanical stenosis were due to the lengthening by the conduit. Seventy-five patients had other complications, the most frequent being arrhythmia. One patient was at stage 0 after induction chemoradiotherapy; 26, stage I (9 IA and 17 IB); 43, stage II (19 IA and 24 IB), 55 stage III (49 IIIA and 6 IIIB); and 5, stage IV. Five-year overall survival, cancer-specific survival, and recurrence-free survival rates were 49.2%, 61.8%, and 37.1%, respectively. CONCLUSIONS: PA reconstruction without intraoperative systemic heparinization during resections of NSCLC was performed with a very low risk of thrombosis as well as perioperative bleeding.

Effect of heparinization on promoting angiogenesis of decellularized kidney scaffolds.

Native decellularized extracellular matrix provides an adequate platform for tissues and organs and promotes the development of organogenesis and tissue remodeling. However, thrombosis poses a great challenge that hinders the transplantation for a substantial organ in vivo. Therefore, anticoagulation and re-reendothelialization of organ biological scaffolds are the primary concerns to be addressed before orthotopic transplantation. Herein, a heparinized decellularized kidney scaffold (HEP-DKSs) was prepared using end-point attachment technology, followed by binding the vascular endothelial growth factor (VEGF) to greatly improve the hemocompatibility and angiogenesis of DKSs. Based on the anticoagulant, co-culture of human umbilical vein endothelial cells, and subcapsular transplantation of kidney experiments, HEP-VEGF-DKSs are shown to reduce platelet adhesion, which is crucial for subsequent vascularization and slow release of heparin and VEGF, suggesting its ability of improve neovascularization. Taken together, these data indicated an optimal anticoagulation function of HEP-VEGF-DKSs and the potential of vascularization for regeneration of whole decellularized kidney.

Comparison of anticoagulation strategies for veno-venous ECMO support in acute respiratory failure.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) support in acute respiratory failure may be lifesaving, but bleeding and thromboembolic complications are common. The optimal anticoagulation strategy balancing these factors remains to be determined. This retrospective study compared two institutional anticoagulation management strategies focussing on oxygenator changes and both bleeding and thromboembolic events. METHODS: We conducted a retrospective observational cohort study between 04/2015 and 02/2020 in two ECMO referral centres in Germany in patients receiving veno-venous (VV)-ECMO support for acute respiratory failure for > 24 h. One centre routinely applied low-dose heparinization aiming for a partial thromboplastin time (PTT) of 35-40 s and the other routinely used a high-dose therapeutic heparinization strategy aiming for an activated clotting time (ACT) of 140-180 s. We assessed number of and time to ECMO oxygenator changes, 15-day freedom from oxygenator change, major bleeding events, thromboembolic events, 30-day ICU mortality, activated clotting time and partial thromboplastin time and administration of blood products. Primary outcome was the occurrence of oxygenator changes depending on heparinization strategy; main secondary outcomes were the occurrence of severe bleeding events and occurrence of thromboembolic events. The transfusion strategy was more liberal in the low-dose centre. RESULTS: Of 375 screened patients receiving VV-ECMO support, 218 were included in the analysis (117 high-dose group; 101 low-dose group). Disease severity measured by SAPS II score was 46 (IQR 36-57) versus 47 (IQR 37-55) and ECMO runtime was 8 (IQR 5-12) versus 11 (IQR 7-17) days (P = 0.003). There were 14 oxygenator changes in the high-dose group versus 48 in the low-dose group. Freedom from oxygenator change at 15 days was 73% versus 55% (adjusted HR 3.34 [95% confidence interval 1.2-9.4]; P = 0.023). Severe bleeding events occurred in 23 (19.7%) versus 14 (13.9%) patients (P = 0.256) and thromboembolic events occurred in 8 (6.8%) versus 19 (19%) patients (P = 0.007). Mortality at 30 days was 33.3% versus 30.7% (P = 0.11). CONCLUSIONS: In this retrospective study, ECMO management with high-dose heparinization was associated with lower rates of oxygenator changes and thromboembolic events when compared to a low-dose heparinization strategy. Prospective, randomized trials are needed to determine the optimal anticoagulation strategy in patients receiving ECMO support.

Heparin concentration in cell salvage during heparinization: a pilot study.

Cell salvage is frequently used to avoid unnecessary allogeneic blood transfusions, which results in a reduction in blood transfusion volume and cost. The aspirated blood is washed with normal saline and centrifuged to recover only blood cells, salvaged blood is then made. In cardiovascular surgery, heparin is used to maintain activated clotting time over 400 seconds. Some practitioners believe that heparin remains in the salvaged blood. Therefore, we hypothesized that salvaged blood during cardiovascular surgery includes heparin. A pilot study was conducted to evaluate our hypothesis using three different salvage systems. This study was a prospective, observational, pilot study, with patients aged 20-85 years old who were scheduled for cardiovascular surgery from May 2018 to October 2018. The intent of this study was to evaluate whether salvaged blood with three different devices includes large enough quantities of heparin to influence activated clotting time in cardiovascular surgery. Between May and October 2018, 12 samples during heparinization were collected, and 12 samples of salvaged blood from 3 devices were collected after administrating protamine. The heparin concentration of the 24 samples was measured. All heparin concentrations in salvage blood sample from two devices was below the limit of measurement (0.10 IU/mL). Slightly measurable heparin was detected in salvaged blood sample from one device (mean 0.15 IU/mL). Salvaged blood during cardiovascular surgery intervention does not contain enough heparin to influence activated clotting time.

Left atrial thrombus formation within a few days of hospitalization in semi-acute ischemic heart disease despite no atrial fibrillation and mitral stenosis: a case report.

BACKGROUND: Currently, the occurrence of left atrial thrombus despite the provision of heparinization within a few days of hospitalization without atrial fibrillation (AF) and mitral stenosis (MS) is rarely reported. CASE PRESENTATION: A 71-year-old woman presented with chest discomfort and dyspnea. Examination revealed ST elevation with sinus rhythm, congestive heart failure, and moderate mitral regurgitation (MR) by transthoracic echocardiography (TTE). Diuretics, a coronary vasodilator, and unfractionated heparin (15,000 units/day) were administered. Four days after hospitalization, her C-reactive protein level had increased; therefore, TTE was repeated, revealing a thrombus in the left atrial appendage, which was probably affected by heparin resistance because of low antithrombin (49%). On day 5, the patient underwent emergency removal of the thrombus, mitral valve replacement, and coronary artery bypass. CONCLUSION: Patients can exhibit low left ventricular contractility, even sinus rhythm without MS. Thus, TTE and subsequent coagulation tests including antithrombin must be performed to prevent thrombus.

Is There a "Blind Spot" in Point-of-Care Testing for Residual Heparin After Cardiopulmonary Bypass? A Prospective, Observational Cohort Study.

Identifying the cause of a bleeding complication after cardiac surgery can be crucial. This study sought to clarify whether the application of unprocessed autologous pump blood influences anti-factor Xa activity after cardiac surgery and evaluated 2 point-of-care methods regarding their ability to identify an elevated anti-factor Xa activity at different timepoints after cardiopulmonary bypass. Anti-factor Xa activity, heparin/protamine titration and the clotting time ratio of thromboelastometry in the INTEM and HEPTEM were measured at baseline (T1), after the application of protamine (T2) and after the complete application of autologous pump blood (T3). Anti-factor Xa activity decreased significantly between T2 and T3 as well did the absolute number of patients with an elevated anti-factor Xa activity. Receiver Operating Curve analyses were performed for both point-of-care methods. At T2 neither could identify patients with an elevated anti-factor Xa activity, while both methods were able to do so at T3 with high sensitivity and specificity. This difference suggests that an interference in the detection of residual heparinization with point-of-care methods exists right after the application of protamine, which seems to subside after a short time span. Nevertheless, results of point-of-care testing for residual heparinization after cardiopulmonary bypass need to be interpreted considering the protamine-heparin ratio and the timepoint of protamine administration.

Impact of delayed systemic heparinization on postoperative bleeding and thromboembolism during post-cardiotomy extracorporeal membrane oxygenation in neonates.

INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation is well-established for pediatric patients with post-cardiotomy heart failure. However, extracorporeal membrane oxygenation support is associated with major complications, that is, hemorrhage and thromboembolism. We seek to report our experience with delayed systemic heparinization during neonatal cardiac extracorporeal membrane oxygenation and its impact on bleeding and thromboembolism. METHODS: We retrospectively identified 15 consecutive neonates who were placed on extracorporeal membrane oxygenation after congenital heart surgery during a period of 3 years (2015-2017). Our anticoagulation protocol consisted of full heparin reversal by protamine after switching from cardiopulmonary bypass to extracorporeal membrane oxygenation (target activated clotting time: 120 ± 20 seconds). Administration of systemic heparinization was delayed until postoperative drainage volume declined to <1 mL/kg/h. Primary study endpoints were thromboembolism, bleeding, and requirement of blood products on extracorporeal membrane oxygenation. RESULTS: Our cohort (mean age: 13 ± 2.6 days; mean weight: 3.1 ± 0.3 kg; 66.7% male) required post-cardiotomy extracorporeal membrane oxygenation with a mean support time of 4.5 ± 2.2 days. Systemic heparinization was delayed averagely for 18.1 ± 9.3 hours. No thromboembolic events were observed on extracorporeal membrane oxygenation or after weaning. Relevant surgical site bleeding occurred in two patients (13.3%) requiring re-thoracotomy on the first postoperative day. Analysis of transfusion volumes revealed 24.5 ± 21.9 mL/kg/d mean packed red blood cells, 9.6 ± 7.1 mL/kg/d mean fresh frozen plasma, and 7.5 ± 5.7 mL/kg/d mean platelets. In-hospital survival was 86.6% (n = 13). CONCLUSION: In this retrospective analysis, the results of delayed systemic heparinization in neonatal post-cardiotomy extracorporeal membrane oxygenation could lead one to conclude that this routine is safe and favorable with low risk for thromboembolic events, reduced postoperative hemorrhage, and reduced blood product utilization.

The Utility of Diffusion-Weighted MRI Lesions to Compare the Effects of Different Heparinization Schemes in Intracranial Aneurysms Treated by Endovascular Intervention.

Objective: Heparinization is applied to prevent ischemic complications in the endovascular treatment of intracranial aneurysms, but there is no unified heparinization scheme. Diffusion-weighted imaging (DWI) can be used to evaluate ischemia after endovascular therapy for intracranial aneurysms. The goal of this study is to apply DWI to evaluate the effects of different heparinization schemes on intracranial aneurysms treated with endovascular therapy. Methods: We retrospectively reviewed 141 patients with 149 aneurysms treated with endovascular interventions from July 2019 to April 2020 at our center, including 96 aneurysms treated with local heparinization and 53 aneurysms treated with systemic heparinization. We collected the basic information of the patients, including age, sex, comorbidities, and aneurysm characteristics, and associated treatment data. New ischemic lesions detected by DWI were categorized belonging to four types. Multivariate logistic regression was used to compare the effects of different heparinization schemes on intracranial aneurysms treated with endovascular therapy. Results: There were no significant differences in age, sex, hypertension, diabetes, and aneurysm size or location between the two groups. The incidence and distribution types of DWI abnormalities in the local heparinization groups and systemic heparinization groups were not significantly different (P > 0.05). There was a correlation between the laser engraving stent and postoperative DWI abnormalities (P < 0.003). Multivariate logistic regression analysis showed that the laser engraving stent was significantly correlated with postoperative DWI abnormalities (odds ratio, 4.71; 95% CI: 1.51-14.58; P = 0.007). Conclusion: Compared with systemic heparinization, local heparinization does not increase the incidence of DWI abnormalities after endovascular treatment, and its application in this group of patients is safe and effective.

Ultrasound-guided Modified Parasternal Intercostal Nerve Block: Role of Preemptive Analgesic Adjunct for Mitigating Poststernotomy Pain.

BACKGROUND AND AIM: To assess the quality and effectiveness of postoperative pain relief after fast-tracking tracheal extubation in cardiac surgery intensive care unit, effected by a single-shot modified parasternal intercostal nerve block compared with routine in-hospital analgesic protocol, when administered before sternotomy. DESIGN: A prospective, randomized, double-blinded interventional study. SETTING: Single-center tertiary teaching hospital. PARTICIPANTS: Ninety adult patients undergoing elective coronary artery bypass grafting surgery under cardiopulmonary bypass. MATERIALS AND METHODS: Patients were randomized into two groups. Patients in the parasternal intercostal block group (PIB) (n = 45) received ultrasound-guided modified parasternal intercostal nerve block with 0.5% levobupivacaine after anesthesia induction at 2nd-6th intercostal space along postinduction using standardized anesthesia drugs with routine postoperative hospital analgesic protocol with intravenous morphine. Patients in the group following routine hospital analgesia protocol (HAP) (n = 45) served as controls, with standardized anesthesia drugs and routine hospital postoperative analgesic protocol with intravenous morphine. The primary study outcome aimed to evaluate pain at rest and when doing deep breathing exercises with spirometry, coughing expectorations using a 11-point numerical rating scale. RESULTS: The postoperative pain score at rest and during breathing exercises was compared between the two groups at different time durations (15 min after extubation and every 4th hourly for 24 h). Patients in the PIB group had significantly lower pain scores and better quality of analgesia during the entire study period at rest and during breathing exercise (P < 0.0001). Furthermore, the side effect profile and need of rescue analgesics were better in the PIB group than the HAP group at different time intervals. CONCLUSION: PIB is safe for presternotomy administration and provided significant quality of pain relief postoperatively, as seen after tracheal extubation for a period of 24 h, on rest as well as with deep breathing, coughing, and chest physiotherapy exercises when compared to intravenous morphine alone after sternotomy. This study further emphasizes the role of preemptive analgesia in mitigating postoperative sternotomy pain and it's role as a plausible safe analgesic adjunct facilitating fast tracking with sternotomies on systemic heparinization.

Early postoperative heparinization reduce hemolysis in patients with HeartMate II devices.

Hemolysis is closely related with pump thrombosis and thromboembolic events in patients with continuous flow left ventricular assist devices. We retrospectively investigated the impact of early postoperative heparinization on hemolysis in patients with HeartMate II devices. From April 2013 to August 2017, 83 patients (age 45 ± 12 years; 20 females; body surface area 1.6 ± 0.2 m2) underwent HeartMate II implantation. Postoperative heparinization was started when hemostasis was achieved and continued until full warfarinization. Hemolysis was defined in accordance with the Interagency Registry for Mechanically Assisted Circulatory Support definitions. The average support period was 22 ± 14 months. The 6-, 12-, and 24-month freedoms from hemolysis were 72%, 70%, and 67%, respectively. Pump thrombosis developed in five (6%) patients and four (5%) required pump exchanges. Heparin start time was significantly later in patients with hemolysis (43 ± 23 h after implantation) versus those without (29 ± 14 h after implantation; p = 0.01). Receiver operating characteristic analysis determined the cut-off point of heparin start time as 29 h. The patients were divided into the early group (heparin start time < 29 h; n = 29), and the late group (heparin start time > 29 h; n = 54). The respective 6-, 12-, and 24-month freedoms from hemolysis for the early group (86%, 86%, and 86%, respectively) were significantly higher than those for the late group (49%, 47%, and 44%, respectively; p = 0.002). Being in the late group was an independent risk factor for hemolysis (hazard ratio 4.09). Early postoperative heparinization (within 29 h after implantation) reduces hemolysis in patients with HeartMate II devices.

How does extracellular matrix-based growth factor delivery system promote osteogenesis? / 中国组织工程研究

BACKGROUND: The local application of growth factor provides a promising therapeutic strategy for the treatment of refractory bone defects. However, there are still many factors that limit the application of the local growth factor delivery system, for example, inability to accurately control the amount of growth factors released and the low biological activity of the released growth factors. OBJECTIVE: To summarize a variety of growth factor delivery systems containing extracellular matrix components and the latest research progress regarding their application in the treatment of bone defects. METHODS: The first authors searched PubMed, Web of Science, Medline, Wanfang and CNKI databases to retrieve articles published during 2007-2019 with the search terms “extracellular matrix, integrins, heparin, heparin, growth factor, controlled delivery system, bone defect” in English and Chinese, respectively. A total of 317 articles were initially retrieved, and 59 of them were included in the final analysis. RESULTS AND CONCLUSION: Extracellular matrix components can combine and regulate the activity of growth factors and improve their bioavailability. Therefore, improvement of growth factor delivery system can be achieved by integrating extracellular matrix components into the growth factor delivery system. Compared with the common growth factor delivery system, the extracellular matrix growth factor delivery system can obtain better growth factor binding effect, higher biological activity and utilization, and even better targeted release, thus producing better effects on promoting bone regeneration. Therefore, the extracellular matrix growth factor delivery system provides a better therapeutic strategy for local treatment of refractory bone defects.