Efficacy of human prothrombin complex concentrate in the treatment of warfarin overdose in patients receiving warfarin for mechanical heart valve replacement.

Warfarin, a widely utilized anticoagulant, is paramount for preventing thromboembolic events in patients with mechanical heart valve replacements. However, its narrow therapeutic index can lead to over-anticoagulation and overdose, resulting in serious health risks. This study examines the efficacy of human prothrombin complex concentrate (PCC) in managing warfarin overdose, in comparison with traditional treatments. A retrospective analysis was conducted on 162 adults who presented with warfarin overdose (INR > 5.0) at a tertiary care hospital between 2016 and 2020. Participants were divided into 2 groups-those treated with PCC (n = 57) and those treated with conventional methods (n = 105), including vitamin K and fresh frozen plasma. The primary outcome was the rate of reaching the target (International Normalized Ratio) INR within 24 hours. Secondary outcomes included transfusion requirements, thromboembolic events, adverse reactions, 30-day mortality, and length of hospital stay. PCC demonstrated significant efficacy, with 89.5% of patients achieving the target INR within 24 hours, compared to 64.8% in the control group (P < .05). The PCC group also had reduced transfusion requirements and a shorter average hospital stay. There was no significant difference in thromboembolic events or adverse reactions between the 2 groups, and the reduced 30-day mortality in the PCC group was not statistically significant. Human prothrombin complex concentrate is associated with rapid reaching the target INR, decreased transfusion needs, and shortened hospitalization, making it a promising option for warfarin overdose management. While the results are encouraging, larger, multicenter, randomized controlled trials are necessary to further validate these findings and optimize PCC administration protocols.

Anesthetic management of a patient with dilated cardiomyopathy and purpura for interventional thrombectomy of both femoral artery: Case report.

RATIONALE: Anesthesia management of patients with dilated cardiomyopathy (DCM) has always been a challenge for anesthesiologists. Eighty percent of patients with DCM have heart failure as the first symptom, which may be accompanied by arrhythmias, thromboembolism, etc. Thrombosis is a significant contributing factor to adverse cardiovascular and cerebrovascular events, and its risk is severely underestimated in the anesthetic management of DCM. PATIENT CONCERNS: We present a case of a 54-year-old hypersensitive female patient with dilated cardiomyopathy and purpura who underwent an interventional thrombectomy under general anesthesia following a lower limb thromboembolism. DIAGNOSIS: Patient underwent an interventional thrombectomy under general anesthesia, with in situ thrombosis occurring during the surgery. INTERVENTIONS: After maintaining stable hemodynamics, proceed with the intervention to retrieve the embolus. OUTCOME: Patients in the advanced DCM developed acute thrombosis twice during embolization. LESSONS: This case discusses the causes of intraoperative thrombosis and summarizes and reflects on the anesthesia management of this case, which has always been one of the difficult points for anesthesiologists to master. In the anesthesia management of DCM patients, it is also necessary to maintain hemodynamic stability, enhance perioperative coagulation management, use anticoagulants rationally, and avoid the occurrence of thrombotic events.

A systematic review of thromboembolic complications and outcomes in hospitalised COVID-19 patients.

Thromboembolic (TE) complications [myocardial infarction (MI), stroke, deep vein thrombosis (DVT), and pulmonary embolism (PE)] are common causes of mortality in hospitalised COVID-19 patients. Therefore, this review was undertaken to explore the incidence of TE complications and mortality associated with TE complications in hospitalised COVID-19 patients from different studies. A literature search was performed using ScienceDirect and PubMed databases using the MeSH term search strategy of "COVID-19", "thromboembolic complication", "venous thromboembolism", "arterial thromboembolism", "deep vein thrombosis", "pulmonary embolism", "myocardial infarction", "stroke", and "mortality". There were 33 studies included in this review. Studies have revealed that COVID-19 patients tend to develop venous thromboembolism (PE:1.0-40.0% and DVT:0.4-84%) compared to arterial thromboembolism (stroke:0.5-15.2% and MI:0.8-8.7%). Lastly, the all-cause mortality of COVID-19 patients ranged from 4.8 to 63%, whereas the incidence of mortality associated with TE complications was between 5% and 48%. A wide range of incidences of TE complications and mortality associated with TE complications can be seen among hospitalized COVID-19 patients. Therefore, every patient should be assessed for the risk of thromboembolic complications and provided with an appropriate thromboprophylaxis management plan tailored to their individual needs.

Emulation of randomized trials of direct oral anticoagulants with claims data and implications for new Factor XI inhibitors.

Direct oral anticoagulants (DOACs) revolutionized the management of thromboembolic disorders. Clinical care may be further improved as Factor XIs undergo large-scale outcome trials. What role can non-randomized database studies play in expediting understanding of these drugs in clinical practice? The RCT-DUPLICATIVE Initiative emulated the design of eight DOAC randomized clinical trials (RCT) using non-randomized claims database studies. RCT study design parameters and measurements were closely emulated by the database studies and produced highly concordant results. The results of the single database study that did not meet all agreement metrics with the specific RCT it was emulating were aligned with a meta-analysis of six trials studying similar questions, suggesting the trial result was an outlier. Well-designed database studies using fit-for-purpose data came to the same conclusions as DOAC trials, illustrating how database studies could complement RCTs for Factor XI inhibitors-by accelerating insights in underrepresented populations, demonstrating effectiveness and safety in clinical practice, and testing broader indications.

Reports on vascular catheter-associated thromboembolic events in a burn unit - a gap in the literature?

Indwelling intravascular catheters are important tools in the care of critically ill patients; however, they have an inherent risk of infection or thromboembolic events. Reports on catheter associated thromboembolic events in burn units are rare, despite being well recognized that burn patients bear an increased baseline risk for thromboembolic events. We describe two catheter-associated thromboembolic complications in burn patients in a burn unit and the morbidity associated with these events. Patients with endovascular catheters in burn units may be at increased risk for severe thromboembolic events associated with intravascular catheters, but specific guidelines for prevention and management of these patients are still missing.

Non-valvular atrial fibrillation in patients on peritoneal dialysis, prevalence, treatment and professionals involved.

Atrial fibrillation is the most frequent chronic arrhythmia in patients with chronic kidney disease. Oral anticoagulation with vitamin K antagonists and now direct oral anticoagulants have been and are the fundamental pillars for the prevention of thromboembolic events. However, there are no randomized clinical trials on the risk-benefit profile of oral anticoagulation in patients with chronic kidney disease stage 5 on peritoneal dialysis and there is little evidence in the literature in this population. The objective of our study was to know the prevalence, treatment and professionals involved in the management of atrial fibrillation in peritoneal dialysis patients. For this purpose, we performed a descriptive analysis through a survey sent to different peritoneal dialysis units in Spain. A total of 1,403 patients on peritoneal dialysis were included in the study, of whom 186 (13.2%) had non-valvular atrial fibrillation. In addition, the assessment of the scores of thromboembolic and bleeding risks for the indication of oral anticoagulation was mainly carried out by the cardiologist (60% of the units), as well as its prescription (cardiologist 47% or in consensus with the nephrologist 43%). In summary, patients on peritoneal dialysis have a remarkable prevalence of non-valvular atrial fibrillation. Patients frequently receive oral anticoagulation with vitamin K antagonists, as well as direct oral anticoagulants. The data obtained regarding the scores used for the assessment of thromboembolic and bleeding risk, treatment and involvement by Nephrology indicates that there is a need for training and involvement of the nephrologist in this pathology.

Anticoagulation for Patients With Concomitant Atrial Fibrillation and End-Stage Renal Disease: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Concomitant atrial fibrillation and end-stage renal disease is common and associated with an unfavorable prognosis. Although oral anticoagulants have been well established to prevent thromboembolism, the applicability in patients under long-term dialysis remains debatable. The study aimed to determine the efficacy and safety of anticoagulation in the dialysis-dependent population. METHODS AND RESULTS: An updated network meta-analysis based on MEDLINE, EMBASE, and the Cochrane Library was performed. Studies published up to December 2022 were included. Direct oral anticoagulants (DOACs, dabigatran, rivaroxaban, apixaban 2.5/5 mg twice daily), vitamin K antagonists (VKAs), and no anticoagulation were compared on safety and efficacy outcomes. The outcomes of interest were major bleeding, thromboembolism, and all-cause death. A total of 42 studies, including 3 randomized controlled trials, with 185 864 subjects were pooled. VKAs were associated with a significantly higher risk of major bleeding than either no anticoagulation (hazard ratio [HR], 1.47; 95% CI, 1.34-1.61) or DOACs (DOACs versus VKAs; HR, 0.74 [95% CI, 0.64-0.84]). For the prevention of thromboembolism, the efficacies of VKAs, DOACs, and no anticoagulation were equivalent. Nevertheless, dabigatran and rivaroxaban were associated with fewer embolic events. There were no differences in all-cause death with the administration of VKAs, DOACs, or no anticoagulation. CONCLUSIONS: For dialysis-dependent populations, dabigatran and rivaroxaban were associated with better efficacy, while dabigatran and apixaban demonstrated better safety. No anticoagulation was a noninferior alterative, and VKAs were associated with the worst outcomes.

Atrial fibrillation ablation compared to pacemaker therapy in patients with tachycardia-bradycardia syndrome: A systematic review and updated meta-analysis.

BACKGROUND: Tachycardia-bradycardia syndrome (TBS) is a subtype of sick sinus syndrome characterized by prolonged sinus pause (≥3 s) following termination of tachyarrhythmias, primarily atrial fibrillation (AF). There is controversy regarding whether the long-term prognosis of AF ablation is superior to pacemaker implantation. This study aimed to compare the effects of AF ablation and pacemaker therapy in patients with TBS. METHODS: We conducted a comprehensive search of electronic databases, including PubMed, Cochrane, EmBase, Web of Science, and Chinese BioMedical, up until December 1, 2023. We included studies that reported the effects of AF ablation vs pacemaker therapy in patients with TBS. From this search, we identified 5 studies comprising 843 participants with TBS who underwent catheter AF ablation or pacemaker therapy. RESULTS: Our meta-analysis revealed that AF ablation and pacemaker therapy had similar effects on cardiovascular death (odds ratio [OR] = 0.62 and 95% confidence interval [CI]: 0.14-2.65), procedural complications (OR = 1.53 and 95% CI: 0.67-3.48), and cardiovascular rehospitalization (OR = 0.57 and 95% CI: 0.26-1.22). However, AF ablation provided greater benefits than pacemaker therapy in terms of all-cause mortality (OR = 0.37 and 95% CI: 0.17-0.82), thromboembolism (OR = 0.25 and 95% CI: 0.12-0.49), stroke (OR = 0.28 and 95% CI: 0.13-0.57), heart failure (OR = 0.27 and 95% CI: 0.13-0.56), freedom from AF (OR = 23.32 and 95% CI: 7.46-72.92), and prevention of progression to persistent AF (OR = 0.12 and 95% CI: 0.06-0.24). Furthermore, AF ablation resulted in a reduced need for antiarrhythmic agents (OR = 0.21 and 95% CI: 0.08-0.59). CONCLUSION: AF ablation can effectively reduce the risk of all-cause mortality, thromboembolism, stroke, heart failure, and progression to persistent AF in patients with TBS. Additionally, it may eliminate the need for further pacemaker therapy in most cases after ablation. Therefore, AF ablation is considered superior to pacemaker therapy in the management of patients with TBS.

Use of apixaban in adults with congenital heart disease and atrial arrhythmias: The PROTECT-AR study.

BACKGROUND: Adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) face an increased risk of thromboembolic events. Limited data exist on the use of non-vitamin K oral anticoagulants for thromboprophylaxis in ACHD. We aimed to assess the effectiveness and safety of apixaban in ACHD patients with AA. METHODS: PROTECT-AR (NCT03854149) was a prospective, multicenter, observational study conducted from 2019 to 2023. ACHD patients with atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia on routine apixaban treatment were included. The historical control group consisted of patients previously on vitamin K antagonist (VKA), who were analyzed prior to their transition to apixaban. The primary effectiveness endpoint was the composite of stroke or thromboembolism. The primary safety endpoint was major bleeding. RESULTS: The study enrolled 218 ACHD patients with AA on apixaban, of which 73 were previous VKA users. The analysis covered 527 patient-years of prospective exposure to apixaban and 169 patient-years of retrospective exposure to VKA. The annualized rate of stroke or thromboembolism was 0.6% in the apixaban group and 1.8% in the VKA group (absolute difference - 1.2%; upper limit of one-sided 95% confidence interval [CI] 0.9%, lower than the predefined non-inferiority margin of +1.8%, Pnon-inferiority < 0.001). The annualized rate of major bleeding was 1.5% in the apixaban group and 2.4% in the VKA group (hazard ratio 0.64; 95% CI 0.19-2.10, P = 0.48). CONCLUSION: In ACHD patients with AA, routine apixaban use exhibited a non-inferior rate of stroke or thromboembolism compared to historical VKA use, alongside a similar rate of major bleeding.

Treatment outcomes in patients with acute thromboembolic occlusion of the superior mesenteric artery.

OBJECTIVES: The goals of this study were to investigate the treatment outcomes of acute thromboembolic occlusion of the superior mesenteric artery (ATOS) and identify prognostic factors after treatment. METHODS: The clinical data of 62 patients with ATOS between 2013 and 2021 were retrospectively reviewed. Patients were stratified by the treatment strategy, complications and mortality were compared in different group. RESULTS: Sixty-two consecutive patients were identified with ATOS. The median patient age was 69 years (interquartile range 58-79 years). Endovascular therapy was initiated in 21 patients, and 4 patients received conservative treatment. Open surgery was performed first in the remaining 37 patients. The technical success rates of the endovascular first group and open surgery group were 90.5% and 97.3%, respectively. One patient in the conservative treatment group had progression of ischemia to extensive bowel necrosis. There was no difference in 30-day mortality between these groups. Predictors of 30-day mortality included initial neutrophil count > 12* 103/dL, age over 60 years old and history of chronic renal insufficiency. CONCLUSIONS: Endovascular treatment or conservative treatment may be adopted in selected patients who do not exhibit signs and symptoms of bowel necrosis, and close monitoring for bowel necrosis is important. The increase in preoperative neutrophil count, age over 60 years old and history of chronic renal insufficiency were poor prognostic factors.

Efficacy and safety of tranexamic acid in patients undergoing thoracic surgery: a systematic review and PRIMSA-compliant meta-analysis.

OBJECTIVES: Perioperative bleeding poses a significant issue during thoracic surgery. Tranexamic acid (TXA) is one of the most commonly used antifibrinolytic agents for surgical patients. The purpose of the current study was designed to investigate the efficacy and safety of TXA in patients undergoing thoracic surgery. METHODS: An extensive search of PubMed, Web of Science (WOS), Cochrane Library (trials), Embase, OVID, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP electronic databases was performed to identify studies published between the inception of these databases and March 2023. The primary outcomes included perioperative blood loss and blood transfusions. Secondary outcomes of interest included the length of stay (LOS) in hospital and the incidence of thromboembolic events. Weighted mean differences (WMDs) or odds ratios (OR) with 95% confidence intervals (CI) were used to determine treatment effects for continuous and dichotomous variables, respectively. RESULTS: Five qualified studies including 307 thoracic surgical patients were included in the current study. Among them, 65 patients were randomly allocated to the group receiving TXA administration (the TXA group); the other 142 patients were assigned to the group not receiving TXA administration (the control group). TXA significantly reduced the quantity of hemorrhage in the postoperative period (postoperative 12h: WMD = -81.90 ml; 95% CI: -139.55 to -24.26; P = 0.005; postoperative 24h: WMD = -97.44 ml; 95% CI: -121.44 to -73.44; P< 0.00001); The intraoperative blood transfusion volume (WMD = -0.54 units; 95% CI: -1.06 to -0.03; P = 0.04); LOS in hospital (WMD = -0.6 days; 95% CI: -1.04 to -0.16; P = 0.008); And there was no postoperative thromboembolic event reported in the included studies. CONCLUSIONS: The present study demonstrated that TXA significantly decreased blood loss within 12 and 24 hours postoperatively. A qualitative review did not identify elevated risks of safety outcomes such as thromboembolic events. It also suggested that TXA administration was associated with shorter LOS in hospital as compared to control. To validate this further, additional well-planned and adequately powered randomized studies are necessary.

The Relationship Between Preoperative International Normalized Ratio and Postoperative Major Bleeding in Total Shoulder Arthroplasty.

INTRODUCTION: This study aimed to assess the relationship between preoperative international normalized ratio (INR) levels and major postoperative bleeding events after total shoulder arthroplasty (TSA). METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for TSA from 2011 to 2020. A final cohort of 2405 patients with INR within 2 days of surgery were included. Patients were stratified into four groups: INR ≤ 1.0, 1.0 < INR ≤ 1.25, 1.25< INR ≤ 1.5, and INR > 1.5. The primary outcome was bleeding requiring transfusion within 72 hours, and secondary outcome variables included complication, revision surgery, readmission, and hospital stay duration. Multivariable logistic and linear regression analyses adjusted for relevant comorbidities were done. RESULTS: Of the 2,405 patients, 48% had INR ≤ 1.0, 44% had INR > 1.0 to 1.25, 7% had INR > 1.25 to 1.5, and 1% had INR > 1.5. In the adjusted model, 1.0 < INR ≤ 1.25 (OR 1.7, 95% CI 1.176 to 2.459), 1.25 < INR ≤ 1.5 (OR 2.508, 95% CI 1.454 to 4.325), and INR > 1.5 (OR 3.200, 95% CI 1.233 to 8.302) were associated with higher risks of bleeding compared with INR ≤ 1.0. DISCUSSION: The risks of thromboembolism and bleeding lie along a continuum, with higher preoperative INR levels conferring higher postoperative bleeding risks after TSA. Clinicians should use a patient-centered, multidisciplinary approach to balance competing risks.

Outcomes of Patients with Preoperative Thrombocytosis After Hip Fracture Surgery.

INTRODUCTION: Low platelet counts have clinically relevant effects on patient outcomes after hip fracture surgery; however, the relationship between abnormally high platelet counts and postoperative outcomes in this population is unknown. METHODS: The ACS-NSQIP database was queried for patients who underwent hip fracture surgery between 2015 and 2019. Outcomes were compared between patients with normal platelet counts (150,000 to 450,000/µL) and thrombocytosis (>450,000/µL). RESULTS: Eighty-six thousand three hundred eleven hip fracture patients were identified, of which 1067 (1.2%) had preoperative thrombocytosis. Compared with patients with normal platelet counts, patients with preoperative thrombocytosis had increased rates of 30-day mortality (6.4% vs 4.5%, P = 0.004; OR 1.15 [95% CI 0.88 to 1.50], P = 0.322) as well as increased rates and odds of readmission (11.4% vs 7.8%, P < 0.001; OR 1.35 [95% CI 1.10 to 1.65], P = 0.004) and venous thromboembolic events (3.2% vs 1.7%, P < 0.001; OR 1.88 [95% CI 1.31 to 2.71], P < 0.001). CONCLUSIONS: Hip fracture patients with preoperative thrombocytosis had increased rates of early mortality as well as increased odds of venous thromboembolic events and readmission. A patient with thrombocytosis may benefit from close postoperative surveillance and careful follow-up. Future prospective studies are needed to verify causation and investigate how to mitigate adverse outcomes in hip fracture patients with preoperative thrombocytosis.

Reversal and resumption of anticoagulants in patients with anticoagulant-associated intracerebral hemorrhage.

The use of anticoagulants has become more frequent due to the progressive aging population and increased thromboembolic events. Consequently, the proportion of anticoagulant-associated intracerebral hemorrhage (AAICH) in stroke patients is gradually increasing. Compared with intracerebral hemorrhage (ICH) patients without coagulopathy, patients with AAICH may have larger hematomas, worse prognoses, and higher mortality. Given the need for anticoagulant reversal and resumption, the management of AAICH differs from that of conventional medical or surgical treatments for ICH, and it is more specific. Understanding the pharmacology of anticoagulants and identifying agents that can reverse their effects in the early stages are crucial for treating life-threatening AAICH. When patients transition beyond the acute phase and their vital signs stabilize, it is important to consider resuming anticoagulants at the right time to prevent the occurrence of further thromboembolism. However, the timing and strategy for reversing and resuming anticoagulants are still in a dilemma. Herein, we summarize the important clinical studies, reviews, and related guidelines published in the past few years that focus on the reversal and resumption of anticoagulants in AAICH patients to help implement decisive diagnosis and treatment strategies in the clinical setting.

Prophylactic-dose direct oral anticoagulants for non-hospitalised people with COVID-19: A meta-analysis of randomised controlled trials.

Background: Several reviews have been conducted on thromboprophylaxis in non-hospitalised patients with coronavirus disease 2019 (COVID-19). In this systematic review and meta-analysis, we sought to investigate the impact of prophylactic-dose direct oral anticoagulants (DOACs) in this population. Methods: We searched PubMed, Web of Science, EMBASE and Cochrane Library for randomised controlled trials (RCTs) comparing prophylactic-dose DOACs with placebo or no treatment in non-hospitalised patients with COVID-19 until September 2023. The primary efficacy outcome was a composite of all-cause mortality and thromboembolic events, while major bleeding events were the primary safety outcome. We expressed continuous outcome data as mean differences (MDs) with 95% confidence intervals (CIs) and dichotomous outcome data as risk ratios (RRs) with 95% CIs. Results: We included six RCTs involving 4307 patients. Prophylactic-dose DOAC therapy compared with placebo or no treatment was associated with significantly decreased risks of the composite outcome of all-cause mortality and thromboembolic events (1.43% vs 2.67% (RR = 0.53; 95% CI = 0.34-0.82, P = 0.004, I2 = 3%)). Major bleeding events were infrequent, and we detected no significant differences between patients assigned to prophylactic-dose DOACs vs placebo or no treatment (0.19% vs 0.05% (RR = 2.50; 95% CI = 0.49-12.87, P = 0.27, I2 = 0%)). The use of prophylactic-dose DOACs was also associated with a reduction in venous thromboembolism, with no difference in all-cause mortality, arterial thromboembolism, hospitalisations, and clinically relevant nonmajor bleeding between two groups. Sensitivity analyses with the leave-one-out method for the primary efficacy and safety outcome did not change the effect estimate substantially. Conclusions: We found that prophylaxis-dose DOACs could significantly improve clinical outcomes and reduce venous thrombotic events without increasing the risk of major bleeding events compared with placebo or no treatment in non-hospitalised patients with COVID-19. Registration: PROSPERO: CRD42023466889.

Incidence of thromboembolic events in non-small cell lung cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

ABSTRACT: The incidence of thromboembolic events (TEs) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) has rarely been reported. The MEDLINE, EMBASE, and the Cochrane Library databases were searched. The primary outcome was the incidence of TEs, and the secondary outcome was the relationship between TEs and overall survival (OS) following ICI therapy. A subgroup analysis of TE incidents was performed according to the TE type and combination regimens. The I2 statistic was used to determine the heterogeneity, and funnel plots and Egger's test were used to assess publication bias. A total of 16,602 patients with NSCLC in 63 experimental arms were included in the analysis. The rate of TEs ranged from 0.1% to 13.8%, and the pooled overall incidence of all-grade TEs was 3% (95% confidence interval [CI], 2%-4%). The pooled rate of high-grade TEs was 1% (95% CI, 1%-2%). The venous and arterial TE rates were 3% (95% CI, 2%-4%) and 1% (95% CI, 1%-2%), respectively. Patients who received immunotherapy + chemoradiotherapy had the highest incidence of TEs (7%). The TE pooled rate was higher in patients treated with combined ICIs than in those treated with mono ICIs (4% vs. 2%). The OS was lower in patients with TEs than in those without TEs (hazard ratio, 1.4; 95% CI, 1.02%-1.92%). The incidence of TEs in NSCLC patients treated with ICIs was reasonable. Nonetheless, clinicians must be aware of potential thrombotic complications and treat them promptly.

Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta-analysis.

Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease as well as the therapies themselves. Overall, available evidence is inconclusive about the differential thrombogenicity of carfilzomib/lenalidomide/dexamethasone (KRd) and bortezomib/lenalidomide/dexamethasone (VRd). This meta-analysis compares the risk for venous thromboembolism (VTE; including deep venous thrombosis and pulmonary embolism) and arterial thromboembolism (ATE; including myocardial infarction and ischemic stroke) with KRd versus VRd as primary therapy for newly diagnosed MM (NDMM). Out of 510 studies identified after deduplication, one randomized controlled trial and five retrospective cohort studies were included. We analyzed 2304 patients (VRd: 1380; KRd: 924) for VTE events and 2179 patients (VRd: 1316; KRd: 863) for ATE events. Lower rates of VTE were observed in the VRd group when compared with the KRd group (6.16% vs. 8.87%; odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.88; p = .01). Both treatment groups exhibited minimal ATE incidence, with no significant difference between them (0.91% vs. 1.16%; OR, 1.01; 95% CI, 0.24-4.20; p = .99). In view of potential biases from retrospective studies, heterogeneity of baseline population characteristics, and limited access to patient-level data (e.g., VTE risk stratification and type of thromboprophylaxis regimen used) inherent to this meta-analysis, additional research is warranted to further validate our findings and refine strategies for thrombosis prevention in MM.

Left atrial appendage occlusion: On the need of a numerical model to simulate the implant procedure.

Left atrial appendage occlusion (LAAO) is a percutaneous procedure to prevent thromboembolism in patients affected by atrial fibrillation. Despite its demonstrated efficacy, the LAA morphological complexity hinders the procedure, resulting in postprocedural drawbacks (device-related thrombus and peri-device leakage). Local anatomical features may cause difficulties in the device's positioning and affect the effectiveness of the device's implant. The current work proposes a detailed FE model of the LAAO useful to investigate implant scenarios and derive clinical indications. A high-fidelity model of the Watchman FLX device and simplified parametric conduits mimicking the zone of the LAA where the device is deployed were developed. Device-conduit interactions were evaluated by looking at clinical indicators such as device-wall gap, possible cause of leakage, and device protrusion. As expected, the positioning of the crimped device before the deployment was found to significantly affect the implant outcomes: clinician's choices can be improved if FE models are used to optimize the pre-operative planning. Remarkably, also the wall mechanical stiffness plays an important role. However, this parameter value is unknown for a specific LAA, a crucial point that must be correctly defined for developing an accurate FE model. Finally, numerical simulations outlined how the device's configuration on which the clinician relies to assess the implant success (i.e., the deployed configuration with the device still attached to the catheter) may differ from the actual final device's configuration, relevant for achieving a safe intervention.