Citations

Following decades of decline, maternal mortality began to rise in the United States around 1990—a significant departure from the world’s other affluent countries. By 2018, the same could be seen with the maternal mortality rate in the United States at 17.4 maternal deaths per 100 000 live births. When factoring in race/ethnicity, this number was more than double among non-Hispanic Black women who experienced 37.1 maternal deaths per 100 000 live births. More than half of these deaths and near deaths were from preventable causes, with cardiovascular disease being the leading one. In an effort to amplify the magnitude of this epidemic in the United States that disproportionately plagues Black women, on June 13, 2020, the Association of Black Cardiologists hosted the Black Maternal Heart Health Roundtable—a collaborative task force to tackle the maternal health crisis in the Black community. The roundtable brought together diverse stakeholders and champions of maternal health equity to discuss how innovative ideas, solutions and opportunities could be implemented, while exploring additional ways attendees could address maternal health concerns within the health care system. The discussions were intended to lead the charge in reducing maternal morbidity and mortality through advocacy, education, research, and collaborative efforts. The goal of this roundtable was to identify current barriers at the community, patient, and clinician level and expand on the efforts required to coordinate an effective approach to reducing these statistics in the highest risk populations. Collectively, preventable maternal mortality can result from or reflect violations of a variety of human rights—the right to life, the right to freedom from discrimination, and the right to the highest attainable standard of health. This is the first comprehensive statement on this important topic. This position paper will generate further research in disparities of care and promote the interest of others to pursue strategies to mitigate maternal mortality.

Objectives The purpose of this study was to explore the utility of an injectable purified exosome product derived from human apheresis blood to (1) augment surgical closure of vaginal mesh exposures, and (2) serve as a stand-alone therapy for vaginal mesh exposure. Methods Sixteen polypropylene meshes (1×1–3×3 cm) were implanted in the vaginas of 7 Yorkshire-crossed pigs by urogynecologic surgeons (day 0). On day 7, group 1 underwent surgical intervention via vaginal tissue suture reclosure with (n=2 pigs, n=4 meshes) or without (n=2 pigs, n=4 meshes) exosome injection; group 2 underwent medical intervention with an exosome injection (n=3, n=8 meshes). One animal in group 2 was given oral 2′-deoxy-5-ethynyluridine to track cellular regeneration. Euthansia occurred at 5 weeks. Results Mesh exposures treated with surgical closure alone experienced reexposure of the mesh. Exosome treatment with or without surgical closure resulted in partial to full mesh exposure resolution up to 3×3 cm. Exosome-treated tissues had significantly thicker regenerated epithelial tissue (208 μm exosomes-only and 217 μm surgery+exosomes, versus 80 μm for surgery-only; P < 0.05); evaluation of 2′-deoxy-5-ethynyluridine confirmed de novo regeneration throughout the epithelium and underlying tissues. Capillary density was significantly higher in the surgery+exosomes group ( P = 0.03). Surgery-only tissues had a higher inflammatory and fibrosis response as compared with exosome-treated tissues. Conclusions In this pilot study, exosome treatment augmented healing in the setting of vaginal mesh exposure, reducing the incidence of mesh reexposure after suture closure and decreasing the area of mesh exposure through de novo tissue regeneration after exosome injection only. Further study of varied local tissue conditions and mesh configurations is warranted.

Abstract OBJECTIVE Glioblastoma (GBM) is the most common malignant primary brain tumor in adults, with males more commonly affected than females(1.6:1). Despite advancements in treatments, prognosis is dismal with a median overall survival of 15 months. Our aim was to investigate sex as a variable in GBM patient survival after receiving incremental levels of standard-of-care treatment regimens – different extents of surgical resection and different numbers of cycles of adjuvant temozolomide chemotherapy. METHODS Drawing from our extensive multi-institutional brain tumor repository, we investigated GBM subjects with overall survival (OS), extent of resection (EOR), number of temozolomide (TMZ) cycles, and sex data (n=620, males: n=387, females: n=233). Cox proportional hazard ratios were computed to investigate the multivariable predictive value of the patient variables with OS. Patients were then divided into groups based on their sex, EOR (either biopsy, subtotal resection (STR) or gross total resection (GTR)), and TMZ cycles (I: &lt; 6 cycles, II: 7-11 cycles and III: &gt;12 cycles). RESULTS We observed that STR was beneficial for females (HR=0.52; CI=0.33-0.83; p-value=0.013), while for males the benefit was not detected (HR=0.73; CI=0.46-1.15; p-value=0.173) for STR but was detectable for GTR (HR=0.58, CI=0.37-0.90; p-value=0.014). Females receiving 7-11 cycles of TMZ showed a survival benefit (HR=0.52; CI=0.12-0.53; p-value=0.048) while males in the same group did not (HR=0.74; CI=0.46-1.19; p-value=0.21), in comparison to those in group I of TMZ cycles. No sex differences were identified in patients receiving &lt; =6 cycles or &gt;=12 cycles. CONCLUSION Together, our results contribute to the growing literature that sex differences exist in GBM patients, even in response to standard-of-care therapies. This should be accounted for when designing clinical trials for GBM so that we may advance our pursuit to deliver personalized medicine.

Abstract: Title: Architecture of sample preparation and data governance of Immuno-genomic data collected from bone marrow and peripheral blood samples obtained from multiple myeloma patients In multiple myeloma (MM), the interactions between malignant plasma cells and the bone marrow microenvironment is crucial to fully understand tumor development, disease progression, and response to therapy. The core challenge in understanding those interactions has been the establishment of a standard process and a standard model for handling the data quality workflow and the underlying data models. Here we present the Platform (Figure 1), an integrated data flow architecture designed to create data inventory and process tracking protocols for multi-dimensional and multi-technology immune data files. This system has been designed to inventory and track peripheral blood and bone marrow samples from multiple myeloma subjects submitted for immune analysis under the MMRF Immune Atlas initiative (figure 2), and the processing and storage of Single Cell RNA-seq (scRNA-seq) and Mass Cytometry time-of-flight (CyTOF) data files derived from these immune analyses. While these methods have been previously applied on both tumor and immune populations in MM [2,3], this level of multi-institutional and multi-technology is unique. The Cloud Immune-Precision platform contains standardized protocols and bioinformatics workflows for the identification and categorization of immune cell populations and functional states based upon scRNA-seq gene signatures (ref: Bioinformatics manuscript in submission) and CyTOF protein signatures. Upon further expansion, it will contain high dimensional scRNAseq and CyTOF immune data from both bone marrow and peripheral blood samples from myeloma patients enrolled in the Multiple Myeloma Research Foundation (MMRF) CoMMpass study (NCT01454297) [1] (Figure 3). The architecture covers the automation of data governance protocols, data transformation and ETL model developments that will create an immune proteomic and profiling database and its integration into clinical and genomics databases: e.g. the MMRF CoMMpass clinical trial. This large-scale data integration will establish a cutting-edge Immune-Precision central platform supporting large scale, immune-focused advanced analytics in multiple myeloma patients. This platform will allow researchers to interrogate the relationships between immune transcriptomic and proteomic signatures and tumor genomic features, and their impact on clinical outcomes, to aid in the optimization of therapy and therapeutic sequencing. Furthermore, this platform also promotes the potential to (further) elucidate the mechanisms-of-action of approved and experimental myeloma therapies, drive biomarker discovery, and identify new targets for drug discovery. Figure 1: Cloud Immune-Precision Platform (Integrated data flow architecture designed to create data inventory and process tracking protocols for multi-dimensional and multi-technology immune data files) Figure 2: Sample tracking process architecture Figure 3: Data file creation and repository process tracking References: 1- Settino, Marzia et al. "MMRF-CoMMpass Data Integration and Analysis for Identifying Prognostic Markers." Computational Science - ICCS 2020: 20th International Conference, Amsterdam, The Netherlands, June 3-5, 2020, Proceedings, Part III vol. 12139 564-571. 22 May. 2020, doi:10.1007/978-3-030-50420-5_42 2- Ledergor, Guy et al. "Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma." Nature medicine vol. 24,12 (2018): 1867-1876. doi:10.1038/s41591-018-0269-2 3- Hansmann, Leo et al. "Mass cytometry analysis shows that a novel memory phenotype B cell is expanded in multiple myeloma." Cancer immunology research vol. 3,6 (2015): 650-60. doi:10.1158/2326-6066.CIR-14-0236-T Figure 1 Disclosures Bhasin: Canomiiks Inc: Current equity holder in private company, Other: Co-Founder. Dhodapkar:Amgen: Membership on an entity's Board of Directors or advisory committees, Other; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Other; Janssen: Membership on an entity's Board of Directors or advisory committees, Other; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Other; Lava Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other; Kite: Membership on an entity's Board of Directors or advisory committees, Other.

ObjectivesThe spine is the most common site of bone metastases in differentiated thyroid cancer (DTC). The role of surgery in the management of cervical spine (C‐spine) metastases (CSpM) has not been adequately explored.MethodsThis is a retrospective cohort study at a tertiary referral center from 2002 to 2018. Inclusion criteria were pathologic diagnosis of DTC and imaging/pathologic diagnosis of CSpM. Statistical analysis utilized t tests for continuous variables and χ2 tests for categorical variables. Survival analysis was conducted using Kaplan–Meier curves with univariate and multivariate Cox regressions.ResultsFifty patients with DTC and CSpM were identified. Of those, 16 underwent surgical resection of the C‐spine, whereas 34 did not. The most common presenting symptom was neck pain (N = 37, 74%). Patients in the surgery group were more likely to report a subjective improvement of symptoms (P < .01) and to have local (P < .01) and systemic (P = .04) disease control. Five‐year overall survival was 44.7% for the surgery group (95% confidence interval [CI]: 17.1–69.3) and 11.1% (95% CI: 2.1–28.8) for the nonsurgery group (P = .01). The strongest risk factor for improved overall survival after C‐spine metastasis was local disease control at the C‐spine (multivariate hazard ratio [HR] = 0.32, 95% CI: 0.12–0.85, P = .02). Surgical intervention was significantly associated with improved survival on both univariate (HR = 0. 35, 95% CI: 0.15–0.82, P = .02) and multivariate (HR = 0.37, 95% CI: 0.14–0.98, P = .04) analysis.ConclusionSurgical management of CSpM in differentiated thyroid cancers is associated with significantly improved local disease control and overall survival. Referral to spine surgeons should be considered after diagnosis.Level of EvidenceIV. Laryngoscope, 131:E1741–E1747, 2021

Abstract Myocardial bridges are anatomical entities characterized by myocardium covering segments of coronary arteries. In some patients, the presence of a myocardial bridge is benign and is only incidentally found on autopsy. In other patients, however, myocardial bridges can lead to compression of the coronary artery during systolic contraction and delayed diastolic relaxation, resulting in myocardial ischemia. This ischemia in turn can lead to myocardial infarction, ventricular arrhythmias and sudden cardiac death. Myocardial bridges have also been linked to an increased incidence of atherosclerosis, which has been attributed to increased shear stress and the presence of vasoactive factors. Other studies however, demonstrated the protective roles of myocardial bridges. In this study, using systematic review and a meta‐analytical approach we investigate the prevalence and morphology of myocardial bridges in both clinical imaging and cadaveric dissections. We also discuss the pathophysiology, clinical significance, and management of these anatomical entities.

Abstract In relapsed/refractory Hodgkin lymphoma (R/R HL), immunotherapies such as the anti-programmed death-1 inhibitor pembrolizumab have demonstrated efficacy as monotherapy and are playing an increasingly prominent role in treatment. The CD30/CD16A-bispecific antibody AFM13 is an innate immune cell engager, a first-in-class, tetravalent antibody, designed to create a bridge between CD30 on HL cells and the CD16A receptor on natural killer cells and macrophages, to induce tumor cell killing. Early studies of AFM13 have demonstrated signs of efficacy as monotherapy for patients with R/R HL and the combination of AFM13 with pembrolizumab represents a rational new treatment modality. Here, we describe a phase 1b, dose-escalation study to assess the safety and preliminary efficacy of AFM13 in combination with pembrolizumab in patients with R/R HL. The primary objective was estimating the maximum tolerated dose; the secondary objectives were to assess safety, tolerability, antitumor efficacy, pharmacokinetics, and pharmacodynamics. In this heavily pretreated patient population, treatment with the combination of AFM13 and pembrolizumab was generally well tolerated, with similar safety profiles compared to the known profiles of each agent alone. The combination of AFM13 with pembrolizumab demonstrated an objective response rate of 88% at the highest treatment dose, with an 83% overall response rate for the overall population. Pharmacokinetic assessment of AFM13 in the combination setting revealed a half-life of up to 20.6 hours. This proof-of-concept study holds promise as a novel immunotherapy combination worthy of further investigation. This phase 1b study was registered at www.clinicaltrials.gov as NCT02665650.

Abstract Background Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze days gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies. Methods DG response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N = 62). Kaplan–Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM. Results In patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan–Meier analysis showed significant differences in OS and PFS at DG cutoffs consistent with previously identified values from newly diagnosed GBM using T1-weighted gadolinium-enhanced magnetic resonance imaging (T1Gd). DG scores for bevacizumab monotherapy patients only approached significance for PFS. Cox regression showed that increases of 25 DG on T1Gd imaging were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy patients. Conclusion DG has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.