Citations

Background There has been growing data about the association between D-dimer levels and thrombectomy outcomes in acute ischemic stroke patients (AIS) with no cumulative evidence. This systematic review and meta-analysis aim to discuss and analyze the findings of the current studies to provide more robust evidence in this regard. Methods A systematic search was conducted through PubMed, Web of Science, Embase, and Scopus to retrieve all relevant investigations. A meta-analysis was conducted, and the results were presented in odds ratio (ORs) for binary variables and ratio of means (ROM) for continuous variables, each accompanied by its respective 95% confidence intervals (CIs). Results After searching and screening, 14 studies were included. The analysis showed that the low D-dimer group had significantly higher rates of favorable functional outcome (OR: 4.40; 95%CI: 2.65–7.30; p < 0.001, n = 3) and recanalization (OR: 4.13; 95%CI: 1.57–10.84; p = 0.004, n = 3) than the high one. The association between D-dimer levels and first-pass effect and re-occlusion risk was also demonstrated. Eventually, two studies also demonstrated a significant association between high D-dimer levels and deep venous thrombosis and symptomatic intracranial hemorrhage as post-thrombectomy complications. Conclusion Current evidence indicates a significant association between D-dimer levels and post-thrombectomy outcomes in AIS patients. However, current data are remarkably heterogeneous, and additional comparative investigations are needed.

AbstractWithin the past decade, there have been multiple innovations in the field of nerve surgery. In this review, we highlight critical changes and innovations that have helped advance the field and present opportunities for further study. This includes the modification and clarification of the classification schema for nerve injuries which informs prognosis and treatment, and a refined understanding and application of electrodiagnostic studies to guide patient selection. We provide indications for operative intervention based on this nerve injury classification and propose strategies best contoured for varying injury presentations at differing time points. Lastly, we discuss new developments in surgical techniques and approaches based on these advancements.

Background The angiographic shape of an occlusion, like the clot meniscus sign and the claw sign, has been reported to potentially impact the recanalization rate and clinical outcome in patients undergoing mechanical thrombectomy for acute ischemic strokes. Method Following PRISMA guidelines, a systematic literature search was conducted across PubMed, Scopus, Embase and Web of Science databases. Patients were grouped into clot meniscus/claw sign positive and negative groups based on the definitions obtained from each study. Primary outcomes included technical success, with a meta-analysis performed using a random-effects model to calculate proportions and odds ratios (OR) with 95% confidence intervals (Cl). Results We included seven studies recruiting 1572 patients. The results indicated that the positive and negative groups had comparable first-pass effect (OR 1.95; 95% CI 0.76 to 5.01; P=0.167) and final recanalization (OR 1.36; 95% CI 0.81 to 2.27; P=0.248) rates. However, the rate of having a favorable functional outcome was significantly higher in the positive group than in the negative sign group (OR 1.91; 95% CI 1.25 to 2.92; P<0.003). Within the sign-positive population, the use of contact aspiration was associated with a significantly higher rate of recanalization compared with using a stent retriever (OR 0.18; 95% CI 0.07 to 0.49; P<0.001). This result did not translate into a clinical impact, as both stent retriever and contact aspiration showed comparable rates of functional independence at 3 months (OR 0.22; 95% CI 0.02 to 2.33; P=0.210). Conclusion The presence of the clot meniscus/claw sign is not associated with recanalization outcomes after thrombectomy. However, it might be a good sign to predict which thrombectomy technique might be associated with better recanalization, although current evidence may need further confirmation.

Background Arteriovenous malformations (AVMs) are uncommon cerebral lesions that can cause significant neurological complications. Surgical resection is the gold standard for treatment, but endovascular embolization and stereotactic radiosurgery (SRS) are viable alternatives. Objective To compare the outcomes of endovascular embolization versus SRS in the treatment of AVMs with Spetzler-Martin grades I–III. Methods This study combined retrospective data from 10 academic institutions in North America and Europe. Patients aged 1 to 90 years who underwent endovascular embolization or SRS for AVMs with Spetzler-Martin grades I–III between January 2010 and December 2023 were included. Results The study included 244 patients, including 84 who had endovascular embolization and 160 who had SRS. Before propensity score matching (PSM), complete obliteration at the last follow-up was achieved in 74.5% of the SRS group compared with 57.8% of the embolization group (OR=0.47; 95% CI 0.26 to 0.48; P=0.01). After propensity score matching, SRS still achieved significantly higher occlusion rates at last follow-up (78.9% vs 55.3%; OR=0.32; 95% CI 0.12 to 0.90; P=0.03). Hemorrhagic complications were higher in the embolization group than in the SRS group, although this difference did not reach statistical significance after PSM (13.2% vs 2.6%; OR=5.6; 95% CI 0.62 to 50.47; P=0.12). Similarly, re-treatment rate was higher in the embolization group (10.5% vs 5.3%; OR=2.11; 95% CI 0.36 to 12.31; P=0.40) compared with the SRS group. Conclusion Our findings indicate that SRS has a significantly higher obliteration rate at last follow-up compared with endovascular embolization. Also, SRS has a higher tendency for fewer hemorrhagic complications and lower re-treatment rate. Further prospective studies are needed.

Abstract Background Hypomagnesemia has been correlated with inferior outcomes in patients with large B cell lymphoma (LBCL) undergoing stem cell transplants. As T-cell and myeloid cell dysfunction have been associated with low magnesium conditions, we investigated whether serum magnesium (Mg) levels could predict clinical outcomes in LBCL patients who received chimeric antigen receptor T-cell therapy. Methods Patients with LBCL who received axi-cel under the ZUMA-1 trial or as FDA approved therapy at Mayo Clinic were examined. Serum samples were obtained at specified time points and cytokine analysis was performed. Single cell RNA sequencing was performed on peripheral blood mononuclear cells. The Student T-test, Kruskal Wallis, or Fisher's Exact Tests were used to compare differences in demographics across Mg levels. Survival curves were plotted using the Kaplan-Meier methodology and compared using the Wilcoxon test. Results We found that hypomagnesemia before lymphodepletion chemotherapy predicted for inferior progression-free and overall survival in the pivotal study ZUMA-1 (NCT02348216). These results were validated in an independent cohort of LBCL patients receiving axicabtagene ciloleucel (axi-cel) at Mayo Clinic. Hypomagnesemia correlated with increased inflammatory serum markers and cytokine levels including ferritin, IL-6, IL1Ra, IL-8, and MIP1a. scRNAseq analysis unveiled altered immune interactions between monocytes and T cells with a concordant immune suppressive transcriptome. Conclusions Hypomagnesemia at the time of CAR-T infusion associates with an unfavorable inflammatory profile and decreased response and survival in LBCL patients receiving axi-cel. These findings suggest a potentially actionable prognostic factor for patients with large cell lymphoma undergoing CAR-T.

Stenosis of the left main coronary artery (LM stenosis) is associated with significant mortality and morbidity due to the large area of affected myocardium. Evidence on the use of percutaneous coronary intervention (PCI) for the treatment of LM stenosis is growing. However, the role of Western guidelines on patients in the Asian-Pacific region is unclear due to anatomical variations, substantial heterogeneity in healthcare resources and infrastructure, and the lack of consensus on the optimal management of LM stenosis in the Asia-Pacific region. Hence, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the use of PCI in the management of LM stenosis in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were in support of ‘agree’ or ‘neutral’. The resulting 12 statements provide guidance for clinical practitioners in the region on the use of PCI in the treatment of patients with LM stenosis.

Background and purpose Treatment of recurrent intracranial aneurysms after their initial therapy has been a significant challenge in the field of neurointervention. Recently flow diverters stents are widely used for treating intracranial aneurysms. In this systematic review and meta-analysis, we assessed the safety and efficacy of flow diverter in treating recurrent or recanalized intracranial aneurysms. Methods This meta-analysis is reported following the PRISMA 2020 guidelines. We conducted a systematic review of literature in the PubMed, Embase, Web of Sciences, and Scopus databases. Pooled prevalence and the corresponding 95% are calculated from extracted data using a random-effect model. Results The systematic literature search included 21 studies involving 411 patients, with 135 (32.8%) being male and 276 (67.2%) being females with a total number of 447 aneurysms. The overall rate of adequate occlusion was 90.67% (95% CI: 84.23%–94.65%), and the rates were comparable between the surgery (93.48%), coiling (91.78%), and stenting (85.77%) groups. The overall pooled rate of complete occlusion was 81.80 (95% CI: 71.14%–89.13%). On doing a subgroup analysis, the complete occlusion rates were 89.68%, 84.39%, and 73.47% for the surgery, coiling, and stenting groups, respectively. The overall mortality rate and achieving modified Rankin scale score of 0-2 was 1.28% (95% CI: 0.45%–3.64%) and (95% CI: 89.92%–97.84%), respectively. No significant heterogeneity is noted in the included studies. Conclusion Flow diverter stents are an effective and safe method for retreating recurrent or residual intracranial aneurysms with a high rate of complete and adequate occlusion. The rate of mortality, intracerebral hemorrhage, and overall and procedural complications following using flow diverters for intracranial aneurysms is low.

Abstract The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed). InO-exposed patients were more heavily pretreated (P = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-naïve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-naïve patients (P = .005). With a median follow-up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS; P = .013) and overall survival (OS; P = .006) in univariate analyses; however, prior InO exposure did not influence PFS (hazard ratio, 1.20; 95% confidence interval, 0.71-2.03) in multivariate models. Within InO-exposed patients, InO responders had superior PFS (P = .002) and OS (P &lt; .0001) relative to InO-refractory patients. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (P = .51) and OS (P = .86) for patients receiving InO as bridging therapy or before apheresis. In conclusion, although InO exposure was associated with inferior survival outcomes after brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively affects brexu-cel efficacy. Our data instead imply that InO-exposed recipients of brexu-cel tend to be higher-risk patients with intrinsic adverse leukemia biology.

Abstract Background Breast cancer is one of the most common types of cancer, with around 2.3 million cases diagnosed in 2020. One in five cancer patients develops chronic lymphedema caused by multifactorial triggers and treatment-related factors. This can lead to swelling, skin infections, and limb dysfunction, negatively affecting the patient's quality of life. This retrospective cohort study aimed to determine the associations between demographic and breast cancer characteristics and postoperative cellulitis in breast cancer survivors who underwent lymphovenous bypass surgery (LVB) at Mayo Clinic, Florida. Methods We performed a retrospective chart review. Data were collected retrospectively from 2016 to 2022. Sixty adult breast cancer survivors who underwent LVB were included in the final analysis based on specific inclusion and exclusion criteria. Patients were excluded if they did not meet the inclusion criteria or had incomplete follow-up data. Demographic and surgical data were extracted, including body mass index (BMI), type of anastomosis, number of anastomoses, and preoperative cellulitis status. Lymphedema measurements were performed using tape measurements. Fisher's exact test was used to determine statistically significant associations between variables and postoperative cellulitis. Results Postoperative cellulitis was more common in patients aged 60 to 69 years (43.2%), whites (75.0%), overweight or obese (90.9%), with one to four anastomoses (81.8%), and nonsmokers (79.5%). The mean International Society of Lymphology (ISL) criteria for both postoperative cellulitis and no postoperative cellulitis was 1.93. Statistically significant associations with postoperative cellulitis were found for the number of anastomoses (p = 0.021), smoking status (p = 0.049), preoperative cellulitis (p = 0.04), and the length of years with lymphedema diagnosis variable (p = 0.004). Conclusion Our results suggest that a greater number of anastomoses, smoking, preoperative cellulitis, and years with lymphedema are significantly associated with an increased risk of postoperative cellulitis. Awareness of these risk factors is crucial for monitoring and early treatment of infections following surgery.

Abstract Extracellular vesicle (EV) secretion is mediated by purinergic receptor P2X 7 (P2RX7), an ATP‐gated cation channel highly expressed in microglia. We have previously shown that administration of GSK1482160, a P2RX7 selective inhibitor, suppresses EV secretion from murine microglia and prevents tauopathy development, leading to the recovery of the hippocampal function in PS19 mice, expressing P301S tau mutant. It is yet unknown, however, whether the effect of GSK1482160 on EV secretion from glial cells is specifically regulated through P2RX7. Here we tested GSK1482160 on primary microglia and astrocytes isolated from C57BL/6 (WT) and P2rx7 –/– mice and evaluated their EV secretion and phagocytotic activity of aggregated human tau (hTau) under ATP stimulation. GSK1482160 treatment and deletion of P2rx7 significantly reduced secretion of small and large EVs in microglia and astrocytes in both ATP stimulated or unstimulated condition as determined by nanoparticle tracking analysis, CD9 ELISA and immunoblotting of Tsg101 and Flotilin 1 using isolated EVs. GSK1482160 treatment had no effect on EV secretion from P2rx7 –/– microglia while we observed significant reduction in the secretion of small EVs from P2rx7 –/– astrocytes, suggesting its specific targeting of P2RX7 in EV secretion except small EV secretion from astrocytes. Finally, deletion of P2rx7 suppressed IL‐1β secretion and phagocytosed misfolded tau from both microglia and astrocytes. Together, these findings show that GSK1482160 suppresses EV secretion from microglia and astrocytes in P2RX7‐dependment manner, and P2RX7 critically regulates secretion of IL‐1β and misfolded hTau, demonstrating as the viable target of suppressing EV‐mediated neuroinflammation and tau propagation.