Introduction
Transcatheter mitral valve replacement (TMVR) is an option for patients at high risk for mitral valve replacement or repair via sternotomy or left thoracotomy approach. TMVR carries up ...to 22% risk of left ventricular outflow tract (LVOT) obstruction. Severe LVOT obstruction can have devastating hemodynamic and clinical consequences.
Hypothesis
We previously presented a novel technique to prevent LVOT obstruction during transapical retrograde mitral valve replacement, by penetrating and ballooning the anterior mitral leaflet (AML), resulting in creation of a “hole” and posterior translocation of AML, then deploying the valve.
Methods
Three patients underwent TMVR at Saint Louis University for severe mitral regurgitation after being deemed too high risk for surgery, and not candidates for a Mitra‐clip procedure. These patients were deemed to be at risk for LVOT obstruction based on the preprocedural evaluation. Via transapical approach, a needle was advanced “through,” perforating the AML and wire was placed in the left atrium. Over the wire, an 20‐mm valvuloplasty balloon was positioned “within” the anterior leaflet and inflated leading to translocation of the AMVL. Then the valve was deployed.
Results
This novel technique has been performed on three patients at our institution. Sapien S3 transcatheter valves were used in all three patients, with 100% procedural success rate. Intraoperative TEE demonstrated no significant LVOT obstruction, cardiopulmonary bypass time was 42–44 min.
Conclusion
The balloon assisted translocation of the mitral anterior leaflet to prevent left ventricular outflow obstruction technique described here may offer the option of transcatheter mitral valve implantation in patients at high risk of LVOT obstruction. A variation of this technique to allow application in cases with transseptal approach is under investigation.
•We optimize location of emerging facilities under competition and uncertainties.•The biofuel and food industry is used as the context for model development.•A Stackelberg–Nash game encompasses the ...biofuel vs. food industry, and farmers.•Equilibrium is derived via continuum approximation and functional optimization.•Efficient algorithms are developed and applied to experiments and a case study.
Technological paradigm shifts often come with a newly emerging industry that seeks a viable infrastructure deployment plan to compete against established competitors. Such phenomenon has been repeatedly seen in the field of transportation systems, such as those related to the booming bioenergy production, among others. We develop a game-theoretic modeling framework using a continuum approximation scheme to address the impacts of competition on the optimal infrastructure deployment. Furthermore, we extend the model to incorporate uncertainties in supply/demand and the risk of facility disruptions. Analytical properties of the optimal infrastructure system are obtained, based on which fast numerical solution algorithms are developed. Several hypothetical problem instances are used to illustrate the effectiveness of the proposed algorithms and to quantify the impacts of various system parameters. A large-scale biofuel industry case study for the U.S. Midwest is conducted to obtain additional managerial insights.
Introduction
The evidence on the association between obesity and atrial fibrillation (AF) recurrence was equivocal. We aimed to evaluate the dose‐response relationship between body mass index (BMI) ...and AF recurrence and adverse events.
Methods
A systematic literature search was conducted using PubMed, Europe PMC, EBSCO, ProQuest and Cochrane Library. Obesity was defined as BMI ≥28 kg/m2. The primary outcome was AF recurrence, and the secondary outcome was adverse events. Adverse events were defined as procedure‐related complications and cardio‐cerebrovascular events.
Results
There were a total of 52,771 patients from 20 studies. Obesity was associated with higher AF recurrence (Odds ratio OR 1.30 95% confidence interval CI 1.16‐1.47, P < .001; I2: 72.7%) and similar rate of adverse events (OR 1.21 95% CI 0.87‐1.67, P = .264; I2: 23.9%). Meta‐regression showed that the association varies by age (coefficient: −0.03, P = .024). Meta‐analysis of highest versus lowest BMI showed that the highest group had higher AF recurrence (OR 1.37 95% CI 1.18‐1.58, P < .001; I2: 64.9%) and adverse events (OR 2.02 95% CI 1.08‐3.76, P = .028; I2: 49.5%). The linear association analysis for AF recurrence was not significant (P = .544). The dose‐response relationship for BMI and AF recurrence was nonlinear (pnonlinearity < 0.001), the curve became steeper at 30‐35 kg/m2. For adverse events, an increase of 1% for every 1 kg/m2 increase in BMI (OR 1.01 95% CI 1.00‐1.02, P = .001), the relationship was nonlinear (pnonlinearity = 0.001).
Conclusion
Obesity was associated with higher AF recurrence in patients undergoing catheter ablation. High BMI might be associated with a higher risk for adverse events.
PROSPERO ID: CRD42020198787.
In patients with spinal instability, cord compression, or neurologic deficits, the standard of care is surgery followed by radiation therapy (RT). Recurrence rates after conventional RT remain high. ...The purpose of this study is to prospectively examine the efficacy of postoperative stereotactic body RT (SBRT) in patients who have undergone surgical intervention for spine metastases. We hypothesize that postoperative SBRT to the spine would be associated with higher local control than historical rates after conventional RT.
Thirty-five adult patients with a Karnofsky Performance Status score ≥40 and spine metastases from solid tumors with no prior overlapping RT and target volumes ≤3 consecutive vertebral levels were enrolled. Thirty-three patients were treated. Two patients underwent treatment to 2 target volumes for a total of 35 target volumes. All patients received SBRT 30 Gy in 5 fractions. Patients were followed with neurological examinations and computed tomography and/or magnetic resonance imaging every 3 months. Neurologic function was assessed at the same time points using the American Spinal Injury Association (ASIA) impairment score. Pain was rated according to the 10-point visual analogue scale and MD Anderson Cancer Center brief pain index. Toxicity was recorded according to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4. The primary objective was the rate of radiographic local recurrence at 12 months after completion of SBRT.
Patient characteristics were as follows: 34.3% had radioresistant primaries; 71.4% were ASIA E and the remainder ASIA D; and the median baseline Karnofsky Performance Status score was 70 (range, 50-100). Radiographic and symptomatic local control at 1 year were 90% (95% confidence interval, 76%-98%). The median time to recurrence in these 3 patients was 3.5 months (range, 3.4-5.8 months), all had radiosensitive tumors, and all recurrences were epidural. No patients experienced wound dehiscence, hardware failure, or spinal cord myelopathy. The median time to return to systemic therapy was 0.5 months (range, 0-9.4 months).
This prospective study of postoperative spine SBRT demonstrates excellent local control with low toxicity. These data suggest superior rates of local control compared with conventional RT; however, a formal comparative study is warranted.
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. ...Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery in a mouse orthotopic GBM model.
We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph nodes, and spleen.
Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%-40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon-γ+/tumor necrosis factor-α+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms.
The combination of PD-1 blockade and localized radiation therapy results in long-term survival in mice with orthotopic brain tumors. These studies provide strong preclinical evidence to support combination trials in patients with GBM.
Purpose
Due to the infiltrative nature of glioblastoma (GBM) outside of the contrast-enhancing region on MRI, there is interest in exploring supratotal resections (SpTR) that extend beyond the ...contrast-enhancing portion of the tumor. However, there is currently no consensus on the potential survival benefit of SpTR in GBM compared to gross total resection (GTR). In this study, we compare the impact of SpTR versus GTR on overall survival (OS) of GBM patients.
Methods
We performed a systematic review and meta-analysis of literature published on PubMed, Embase, The Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov, from inception to August 16, 2018, to identify articles comparing OS after SpTR versus GTR.
Results
We identified 8902 unique citations, of which 11 articles met study inclusion criteria. 810 patients underwent SpTR out of a total of 2056 patients. 9 of 11 studies demonstrated improved outcomes with SpTR compared to GTR (median improvement in OS of 10.5 months), with no significant difference in postoperative complication rate. Overall study quality was variable, with ten studies presenting level IV evidence and one study presenting level IIIb evidence. Subgroup meta-analysis based on SpTR definition demonstrated a statistically significant 35% lower risk of mortality in patients who underwent anatomical SpTR compared to patients who underwent GTR (Hazard ratio = 0.65, 95% CI 0.47- 0.91, p = 0.003).
Conclusion
Our systematic review indicates SpTR may be associated with improved OS compared to GTR for GBM, especially with anatomical SpTR. However, this is limited by variable study design and significant clinical and methodological heterogeneity among studies. There is need for prospective clinical data to further guide parameters regarding the use of SpTR in GBM.
Primary CNS neoplasms are responsible for considerable mortality and morbidity, and many therapies directed at primary brain tumors have proven unsuccessful despite their success in preclinical ...studies. Recently, the tumor immune microenvironment has emerged as a critical aspect of primary CNS neoplasms that may affect their malignancy, prognosis, and response to therapy across patients and tumor grades. This review covers the tumor microenvironment of various primary CNS neoplasms, with a focus on glioblastoma and meningioma. Additionally, current therapeutic strategies based on elements of the tumor microenvironment, including checkpoint inhibitor therapy and immunotherapeutic vaccines, are discussed.
Myeloid cells constitute a significant part of the immune system in the context of cancer, exhibiting both immunostimulatory effects, through their role as antigen presenting cells, and ...immunosuppressive effects, through their polarization to myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages. While they are rarely sufficient to generate potent anti-tumor effects on their own, myeloid cells have the ability to interact with a variety of immune populations to aid in mounting an appropriate anti-tumor immune response. Therefore, myeloid therapies have gained momentum as a potential adjunct to current therapies such as immune checkpoint inhibitors (ICIs), dendritic cell vaccines, oncolytic viruses, and traditional chemoradiation to enhance therapeutic response. In this review, we outline critical pathways involved in the recruitment of the myeloid population to the tumor microenvironment and in their polarization to immunostimulatory or immunosuppressive phenotypes. We also emphasize existing strategies of modulating myeloid recruitment and polarization to improve anti-tumor immune responses. We then summarize current preclinical and clinical studies that highlight treatment outcomes of combining myeloid targeted therapies with other immune-based and traditional therapies. Despite promising results from reports of limited clinical trials thus far, there remain challenges in optimally harnessing the myeloid compartment as an adjunct to enhancing anti-tumor immune responses. Further large Phase II and ultimately Phase III clinical trials are needed to elucidate the treatment benefit of combination therapies in the fight against cancer.
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