Evidence supporting interventional pulmonary embolism (PE) treatment is needed.
We aimed to evaluate the acute safety and effectiveness of mechanical thrombectomy for intermediate- and high-risk PE ...in a large real-world population.
FLASH is a multicentre, prospective registry enrolling up to 1,000 US and European PE patients treated with mechanical thrombectomy using the FlowTriever System. The primary safety endpoint is a major adverse event composite including device-related death and major bleeding at 48 hours, and intraprocedural adverse events. Acute mortality and 48-hour outcomes are reported. Multivariate regression analysed characteristics associated with pulmonary artery pressure and dyspnoea improvement.
Among 800 patients in the full US cohort, 76.7% had intermediate-high risk PE, 7.9% had high-risk PE, and 32.1% had thrombolytic contraindications. Major adverse events occurred in 1.8% of patients. All-cause mortality was 0.3% at 48-hour follow-up and 0.8% at 30-day follow-up, with no device-related deaths. Immediate haemodynamic improvements included a 7.6 mmHg mean drop in mean pulmonary artery pressure (-23.0%; p<0.0001) and a 0.3 L/min/m
mean increase in cardiac index (18.9%; p<0.0001) in patients with depressed baseline values. Most patients (62.6%) had no overnight intensive care unit stay post-procedure. At 48 hours, the echocardiographic right ventricle/left ventricle ratio decreased from 1.23±0.36 to 0.98±0.31 (p<0.0001 for paired values) and patients with severe dyspnoea decreased from 66.5% to 15.6% (p<0.0001). Conclusions: Mechanical thrombectomy with the FlowTriever System demonstrates a favourable safety profile, improvements in haemodynamics and functional outcomes, and low 30-day mortality for intermediate- and high-risk PE.
The goal of glioma surgery is maximal safe resection. These intrinsic brain neoplasms, however, lack a clear margin and frequently infiltrate eloquent areas of the brain thus making their surgical ...resection challenging. This review first focuses on discussion of preoperative investigations that aid in anatomical and functional tumor characterization that help define tumor extent and determine the feasibility of complete resection. The second part of this review outlines intraoperative adjuncts that help identify tumor infiltrated tissues during surgery to maximize the extent of resection. In addition, we discuss the principles of intraoperative functional cortical and subcortical mapping and monitoring that enable maximal tumor resection while minimizing the risk of postoperative neurological deficit. Combined use of different modalities before and during surgery is encouraged to meet surgical goals and to ensure best patient outcome.
Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms by which ...glioblastoma-associated myeloid cells (GAMs) undergo metamorphosis into tumor-supportive cells, characterizing the heterogeneity of immune cell phenotypes within glioblastoma subtypes, and discovering new targets can help the design of new efficient immunotherapies. In this study, we performed a comprehensive battery of immune phenotyping, whole-genome microarray analysis, and microRNA expression profiling of GAMs with matched blood monocytes, healthy donor monocytes, normal brain microglia, nonpolarized M0 macrophages, and polarized M1, M2a, M2c macrophages. Glioblastoma patients had an elevated number of monocytes relative to healthy donors. Among CD11b
cells, microglia and MDSCs constituted a higher percentage of GAMs than did macrophages. GAM profiling using flow cytometry studies revealed a continuum between the M1- and M2-like phenotype. Contrary to current dogma, GAMs exhibited distinct immunological functions, with the former aligned close to nonpolarized M0 macrophages.
Abstract
Background
We sought to ascertain the immune effector function of pembrolizumab within the glioblastoma (GBM) microenvironment during the therapeutic window.
Methods
In an open-label, ...single-center, single-arm phase II “window-of-opportunity” trial in 15 patients with recurrent (operable) GBM receiving up to 2 pembrolizumab doses before surgery and every 3 weeks afterward until disease progression or unacceptable toxicities occurred, immune responses were evaluated within the tumor.
Results
No treatment-related deaths occurred. Overall median follow-up time was 50 months. Of 14 patients monitored, 10 had progressive disease, 3 had a partial response, and 1 had stable disease. Median progression-free survival (PFS) was 4.5 months (95% CI: 2.27, 6.83), and the 6-month PFS rate was 40%. Median overall survival (OS) was 20 months, with an estimated 1-year OS rate of 63%. GBM patients’ recurrent tumors contained few T cells that demonstrated a paucity of immune activation markers, but the tumor microenvironment was markedly enriched for CD68+ macrophages.
Conclusions
Immune analyses indicated that pembrolizumab anti–programmed cell death 1 (PD-1) monotherapy alone can’t induce effector immunologic response in most GBM patients, probably owing to a scarcity of T cells within the tumor microenvironment and a CD68+ macrophage preponderance.
Although patients with primary and metastatic brain tumors and their partners are at risk of experiencing high symptom burden, they are often excluded from psychosocial intervention studies. Thus, we ...sought to examine the feasibility and preliminary efficacy of a couple-based meditation (CBM) program targeting symptom and well-being outcomes.
Couples completed baseline measures assessing symptom and well-being outcomes and were randomized to the CBM or a usual care control group. Couples in the CBM groups attended four weekly (60 minutes each) therapist-led sessions that were delivered via FaceTime (Apple Inc, Cupertino, CA). The CBM program focused on cultivating mindfulness, compassion, gratitude and purpose, and integrated emotional disclosure exercises. Both groups were reassessed six and 12 weeks after baseline.
We approached 60 eligible dyads, of which 37 (62%) consented, 35 (95%) were randomized, and 22 (63%) completed all assessments. Couples in the CBM group attended a mean of 3.33 sessions (SD 1.09). For patients, significant group differences in favor of the CBM group were found for cognitive (d = 1.05) and general disease symptoms (d = 0.93), and relationship well-being (d = 0.68) and compassion (d = 0.96). No significant group differences were revealed for partners.
It seems to be feasible, acceptable, and possibly efficacious to deliver a dyadic intervention via FaceTime to brain tumor couples. Although both patients and partners in the CBM group rated the intervention as beneficial, significant group differences with medium-to-large effect sizes were only found for patients.
BackgroundUp to 20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), for which the current standard of care is radiation therapy with or without surgery. There are ...no prospective data on the safety of stereotactic radiosurgery (SRS) concurrent with immune checkpoint inhibitor therapy for BM. This is the safety cohort of the phase I/II investigator-initiated trial of SRS with nivolumab and ipilimumab for patients with BM from NSCLC.Patients and methodsThis single-institution study included patients with NSCLC with active BM amenable to SRS. Brain SRS and systemic therapy with nivolumab and ipilimumab were delivered concurrently (within 7 days). The endpoints were safety and 4-month intracranial progression-free survival (PFS).ResultsThirteen patients were enrolled in the safety cohort, 10 of whom were evaluable for dose-limiting toxicities (DLTs). Median follow-up was 23 months (range 9.7–24.3 months). The median interval between systemic therapy and radiation therapy was 3 days. Only one patient had a DLT; hence, predefined stopping criteria were not met. In addition to the patient with DLT, three patients had treatment-related grade ≥3 adverse events, including elevated liver function tests, fatigue, nausea, adrenal insufficiency, and myocarditis. One patient had a confirmed influenza infection 7 months after initiation of protocol treatment (outside the DLT assessment window), leading to pneumonia and subsequent death from hemophagocytic lymphohistiocytosis. The estimated 4-month intracranial PFS rate was 70.7%.ConclusionConcurrent brain SRS with nivolumab/ipilimumab was safe for patients with active NSCLC BM. Preliminary analyses of treatment efficacy were encouraging for intracranial treatment response.
The object of this study was to describe the utility and safety of using a single probe for combined intraoperative navigation and subcortical mapping in an intraoperative MR (iMR) imaging ...environment during brain tumor resection.
The authors retrospectively reviewed those patients who underwent resection in the iMR imaging environment, as well as functional electrophysiological monitoring with continuous motor evoked potential (MEP) and direct subcortical mapping combined with diffusion tensor imaging tractography. RESULTS As a navigational tool the monopolar probe used was safe and accurate. Positive subcortical fiber MEPs were obtained in 10 (83%) of the 12 cases. In 10 patients in whom subcortical MEPs were recorded, the mean stimulus intensity was 10.4 ± 5.2 mA and the mean distance from the probe tip to the corticospinal tract (CST) was 7.4 ± 4.5 mm. There was a trend toward worsening neurological deficits if the distance to the CST was short, and a small minimum stimulation threshold was recorded indicating close proximity of the CST to the resection margins. Gross-total resection (95%-100% tumor removal) was achieved in 11 cases (92%), whereas 1 patient (8%) had at least a 90% tumor resection. At the end of 3 months, 2 patients (17%) had persistent neurological deficits.
The monopolar probe can be safely implemented in an iMR imaging environment both for navigation and stimulation purposes during the resection of intrinsic brain tumors. In this study there was a trend toward worsening neurological deficits if the distance from the probe to the CST was short (< 5 mm) indicating close proximity of the resection cavity to the CST. This technology can be used in the iMR imaging environment as a surgical adjunct to minimize adverse neurological outcomes.
Several indices have been developed to predict overall survival (OS) in patients with breast cancer with brain metastases, including the breast graded prognostic assessment (breast-GPA), comprising ...age, tumor subtype, and Karnofsky performance score. However, number of brain metastases-a highly relevant clinical variable-is less often incorporated into the final model. We sought to validate the existing breast-GPA in an independent larger cohort and refine it integrating number of brain metastases.
Data were retrospectively gathered from a prospectively maintained institutional database. Patients with newly diagnosed brain metastases from 1996 to 2013 were identified. After validating the breast-GPA, multivariable Cox regression and recursive partitioning analysis led to the development of the modified breast-GPA. The performances of the breast-GPA and modified breast-GPA were compared using the concordance index.
In our cohort of 1,552 patients, the breast-GPA was validated as a prognostic tool for OS (P < .001). In multivariable analysis of the breast-GPA and number of brain metastases (> three v ≤ three), both were independent predictors of OS. We therefore developed the modified breast-GPA integrating a fourth clinical parameter. Recursive partitioning analysis reinforced the prognostic significance of these four factors. Concordance indices were 0.78 (95% CI, 0.77 to 0.80) and 0.84 (95% CI, 0.83 to 0.85) for the breast-GPA and modified breast-GPA, respectively (P < .001).
The modified breast-GPA incorporates four simple clinical parameters of high prognostic significance. This index has an immediate role in the clinic as a formative part of the clinician's discussion of prognosis and direction of care and as a potential patient selection tool for clinical trials.
Objectives
The FlowTriever All‐Comer Registry for Patient Safety and Hemodynamics (FLASH) is a prospective multi‐center registry evaluating the safety and effectiveness of percutaneous mechanical ...thrombectomy for treatment of pulmonary embolism (PE) in a real‐world patient population (NCT03761173). This interim analysis reports outcomes for the first 250 patients enrolled in FLASH.
Background
High‐ and intermediate‐risk PEs are characterized by high mortality rates, frequent readmissions, and long‐term sequelae. Mechanical thrombectomy is emerging as a front‐line therapy for PE that enables immediate thrombus reduction while avoiding the bleeding risks inherent with thrombolytics.
Methods
The primary endpoint is a composite of major adverse events (MAE) including device‐related death, major bleeding, and intraprocedural device‐ or procedure‐related adverse events at 48 h. Secondary endpoints include on‐table changes in hemodynamics and longer‐term measures including dyspnea, heart rate, and cardiac function.
Results
Patients were predominantly intermediate‐risk per ESC guidelines (6.8% high‐risk, 93.2% intermediate‐risk). There were three MAEs (1.2%), all of which were major bleeds that resolved without sequelae, with no device‐related injuries, clinical deteriorations, or deaths at 48 h. All‐cause mortality was 0.4% at 30 days, with a single death that was unrelated to PE. Significant on‐table improvements in hemodynamics were noted, including an average reduction in mean pulmonary artery pressure of 7.1 mmHg (22.2%, p < 0.001). Patient symptoms and cardiac function improved through follow‐up.
Conclusions
These interim results provide preliminary evidence of excellent safety in a real‐world PE population. Reported outcomes suggest that mechanical thrombectomy can result in immediate hemodynamic improvements, symptom reduction, and cardiac function recovery.
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