tbuckley/cabot-search huggingface dataset:
Real-World Treatment Patterns and Outcomes in Patients with Hemophagocytic Lymphohistiocytosis (HLH) and Other Clinical Conditions Treated with Emapalumab: The Real-HLH Study Design
Authors: Carl E. Allen, Jennifer Leiding, Shanmuganathan Chandrakasan, Kelly J. Walkovich, Abiola Oladapo, John Yee, Priti Pednekar, Sajjad Raza, Michael B Jordan
Journal: Blood (2021)
Abstract 10167: Coronavirus Disease 2019 Pandemic and Incidence of Takotsubo Syndrome: A Retrospective Study
Authors: Dyuti Trivedi, Emma Black, Surya Khatri, Janice Tripolone, Emily Gathright, Elena Salmoirago-blotcher
Journal: Circulation (2021)

Introduction: During the Coronavirus Disease 2019 (COVID-19) pandemic individuals have been exposed to unprecedented levels of psychological, social, and financial stress. Given the association between Takotsubo Syndrome (TS) and stress exposure, we hypothesized that the incidence of TS would increase during the Covid-19 pandemic. Methods: We performed a retrospective review of electronic medical records of patients admitted to three large hospitals in RI, United States. The proportion of TS admission (based on Mayo Clinic criteria)/all-cause admissions during the first pandemic year (3/1/2020-2/28/2021) was compared with that of the previous, non-pandemic, year (3/1/2019-2/28/2020). We collected information on demographics, medical history, and length of hospitalization. T-test and chi-square were used to compare continuous and categorical variables, respectively. A p value (2-sided) &lt; .05 was considered significant. Results: The number of all-cause admissions was lower during the pandemic vs. the pre-pandemic year (229,906 vs. 316,299), p &lt; .001. During the pandemic year, 39/229,906 patients were admitted with TS, compared to 35/316,299 in the pre-pandemic period. Characteristics of TS patients were similar except for the duration of hospital stay (Table 1). TS incidence proportion was 0.017% during the pandemic period vs. 0.011% (p .07, Fig. 1), and the rate ratio was 1.53 (95% CI: 0.97, 2.42). Conclusions: Despite the limitations of this study (small sample size; retrospective design), findings suggest the incidence of TS was higher during the pandemic year. These findings need to be confirmed in a larger and more diverse population.
Abstract 12970: Exploring Experiences Associated With Aortic Stenosis Diagnosis, Treatment and Life Impact Among Middle-Aged and Older Adults: An Interview Study
Authors: Kylie Picou, Debbie Heard, Pinak B Shah, Suzanne V Arnold
Journal: Circulation (2021)

Background: Although multiple studies have examined various clinical aspects of diagnosis, treatment, and management of patients with aortic stenosis (AS), there are limited data collected from patients regarding experiences related to symptoms, diagnosis, treatment decisions, and personal impacts of living with AS. Methods: Adults aged ≥40 years diagnosed with AS were recruited from national patient networks and through professional recruiters. Participants were separated into 3 cohorts: medically managed, surgical aortic valve replacement (SAVR), and transcatheter aortic valve implantation (TAVI). Semi-structured interviews were conducted via teleconference using open ended questions and probes. Interview recordings were transcribed verbatim and inductive thematic analyses were conducted. Results: A total of 45 interviews were conducted (15 per treatment group). The majority of participants were male (55.6%, 25 of 45), white (95.6%, 43 of 45), and non-Hispanic (93.3%, 42 of 45). Median time from symptom onset to diagnosis was 6 months (IQR: 1-12). Participants noting longer times to diagnosis reported mild symptom onset and experiences of misdiagnoses. Some participants described that healthcare professionals explained the AS diagnosis clearly and understandably, while others left the encounter confused with unanswered questions. Participants described a strong reliance on their healthcare professionals to guide them through their treatment decisions, which were influenced by the effects of anticoagulation, future valve interventions, and recovery. Medically managed participants reported making lifestyle modifications to manage AS symptoms, including chronic anxiety and fatigue. In contrast, participants who underwent TAVI or SAVR reported positive sentiments, including gratitude and freedom to live life normally following the procedure. Conclusions: The diverse but challenging experiences of individuals with AS suggest that increasing both the availability and use of patient resources may improve patients’ understanding of AS and facilitate informed treatment decisions. Common reports of delayed AS diagnosis also indicate a need for additional healthcare professional education on referral to a heart valve team.
Abstract 10997: Long-Term Prognostic Value of Catheter-Derived Left Ventricular Diastolic Stiffness in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Hideaki Kanzaki, Yuki Irie, takashi kakuta, Atsushi Okada, Makoto Amaki, Naonori Kawamoto, Tomoyuki Fujita, Chisato Izumi
Journal: Circulation (2021)

Introduction: Despite successful transcatheter aortic valve replacement (TAVR), low flow rate (FR) severe aortic stenosis (AS) patients reportedly experienced poorer clinical outcomes than normal FR AS patients. Left ventricular (LV) diastolic function influences stroke volume, though limited data on TAVR outcomes in patients with severe LV diastolic dysfunction is available. Hypothesis: AS patients with severe LV diastolic dysfunction may develop adverse cardiac events, such as heart failure, even after TAVR. Methods: Consecutive patients with severe AS and preserved LV ejection fraction (&gt; 50%) who underwent hemodynamic assessment of LV function using cardiac catheterization before TAVR were enrolled. The average slope of the end-diastolic pressure-volume relationship was calculated to determine LV diastolic stiffness. Adverse cardiac events were defined as cardiac death or heart failure hospitalization. High LV stiffness (&gt; 190 mmHg/L) patients were compared to normal LV stiffness patients. Results: Of the 78 patients (age 83.2 ± 5.1 years; 21 men), 30 (38.5%) were classified to the high LV stiffness group. Low FR (&lt; 200 mL/s) severe AS was more likely in patients with high LV stiffness than in those with normal LV stiffness (66.7% vs 33.3%, P = 0.004). Adverse cardiac events increased in the high LV stiffness group (Figure, Log rank P = 0.054). Cox regression analysis revealed that LV stiffness was associated with increased adverse cardiac events, after adjusting for age, sex, aortic valve area, and renal function (HR, 1.008; 95%CI, 1.001-1.014; P = 0.026). Conclusion: Increased LV stiffness derived from cardiac catheterization was related to low FR and was also associated with poor clinical outcomes after TAVR.
Disease Characteristics of Multiple Myeloma Involving BRAF Mutations
Authors: Shehab Fareed Mohamed, Maliha Khan, Andres Quesada, Junsheng Ma, Pei Lin, C. Cameron Yin, Koji Sasaki, Gautam Borthakur, Naveen Pemmaraju, Qaiser Bashir, Muzaffar H. Qazilbash, Gregory P. Kaufman, Melody R. Becnel
Journal: Blood (2021)
Suppressed Fibrinolytic Activity Demonstrated By Simultaneous Thrombin and Plasmin Generation Assay during Cytokine Release Syndrome after CD19 Chimeric Antigen Receptor-Modified T-Cell Therapy
Authors: Takashi Ishihara, Yasuyuki Arai, Makiko Morita, Tomoko Onishi, Hanako Shimo, Toshio Kitawaki, Akifumi Takaori-Kondo, Soichi Adachi, Keiji Nogami
Journal: Blood (2021)
QOLP-18. QUALITY OF LIFE IN GLIOMAS WHO UNDERWENT AWAKE SURGERY DEPENDS ON RETURN TO SOCIAL LIFE, ABILITY OF MOVEMENT AND VERBAL FLUENCY
Authors: Riho Nakajima, Masashi Kinoshita, Hirokazu Okita, Mitsutoshi Nakada
Journal: Neuro-Oncology (2021)

Abstract Awake surgery is performed aiming for maintaining postoperative quality of life (QOL) by preserving brain function. Nowadays, it is not known whether QOL is certainly maintained in gliomas who underwent awake surgery, and which brain functions contribute to maintain their postoperative QOL. Here we investigated QOL following awake surgery, and to determine their background and functional factors influencing on QOL. Totally 80 patients with gliomas were matched our inclusion criteria. SF-36 was performed for assessment of QOL. Three component scores including physical component summary (PCS), mental component summary (MCS), and role/social component summary (RCS) were calculated, and were compared them with that of normal healthy controls. Additionally, neurological/neuropsychological functions were evaluated at pre- and post-operative six months. Multiple regression analyses were used to investigate functional and sociodemographic/clinical factors influencing on SF-36. RCS but not PCS and MCS in patient group was significantly lower than that of normal controls (p&amp;lt; .0001). Then, we investigated sociodemographic/clinical factors influencing on RCS, and found two significant factors, returning to social life and malignancy grade (p=0.011 and 0.022, respectively). The primary reasons for difficulty in returning to social life were functional deficits including aphasia and paresis. Among functional factors, RCS significantly related to motor function and verbal fluency (p= 0.0042 and 0.040, respectively). To support the results, RCS in deficit group for movement and verbal fluency was significantly low than in non-deficit group (Wilcoxon test, p=0.037 and 0.044, respectively). Among factors influencing on RCS, sociodemographic/clinical factors were returning to social life and malignancy grade, while functional factors were motor function and verbal fluency.
Abstract 12378: Encephaloduroarteryiosinangiosis (EDAS) is a Cost-Effective Treatment for Symptomatic Intracranial Atherosclerosis
Authors: Nestor R Gonzalez, Chi-Hong Tseng, Miguel Quintero-Consuegra, Daniel Chang, Zachary Barnard, George Thomas, Jeffrey L Saver
Journal: Circulation (2021)

Introduction: Encephaloduroarteriosynangiosis (EDAS) is being evaluated as a new treatment for symptomatic-intracranial-atherosclerotic-disease (sICAD) in high-risk patients. We present a cost-effectiveness analysis of EDAS compared with intensive-medical-management (IMM) for sICAD. Hypothesis: EDAS surgery is a cost-effective treatment for sICAD Methods: Clinical data was obtained from the EDAS-Revascularization-for- Symptomatic-Intracranial-Atherosclerotic-Steno-occlusive-Performance-Criterion-trial (ERSIAS-PC) (n=52) and propensity scored matched cohorts from SAMMPRIS and COSS. Outcomes were projected at 3.5 years. Conservatively, treatment-effect was set as annual-risk-reduction (ARR) of 3.4%/year, 55% of the observed effect in stroke-death reduction in ERSIAS-PC. Total costs of procedure and IMM were calculated using disabling stroke, non-disabling stroke, or death rates per group, adjusted to 2021US$. The quality-adjusted-life-year (QALY) of each intervention was estimated using the frequency of disabling and non-disabling stroke, death, and baseline-health. Incremental cost-effectiveness-ratio (ICER) was formulated for 3.5-years. Results: Rates of stroke/death in ERSIAS PC were 9.6% (EDAS+IMM) and 21.2% (IMM). Estimated rates of stroke/death at 3.5 years were 27.9% (EDAS+IMM) and 38.9%(IMM). Calculated net-costs at 3.5-years were US$40,883 (EDAS+IMM) and US$20,968 (IMM) QALYs were 0.77 (EDAS+IMM) and 0.69 (IMM) (range 0-0.89 corresponding to death-baseline health). The cost per QALY gained after EDAS+IMM was US$68,916, and US$63,916 for IMM. The corresponding ICER for EDAS+IMM versus IMM was $65,736, below the threshold of US$189,153 (3xGPD-per-capita) for cost effectiveness. Conclusions: ARR of stroke/death of at least 3.4% after EDAS is a cost-effective strategy for the treatment of high-risk sICAD patients. This ARR is conservative compared to the observed 5.9% ARR in the ERSIAS-PC trial. Further investigation of EDAS in a pivotal/phase III trial is supported as a cost-effective strategy
Supermobilizers with High CD34 + Cell Collection for Autologous Transplant and Impact on Survival Outcomes in Multiple Myeloma
Authors: Eyal Lebel, Katherine Lajkosz, Esther Masih-Khan, Donna E. Reece, Suzanne Trudel, Rodger E Tiedemann, Anca Prica, Vishal Kukreti, Christine I. Chen
Journal: Blood (2021)
recount3: summaries and queries for large-scale RNA-seq expression and splicing
Authors: Christopher Wilks, Shijie C. Zheng, Feng Yong Chen, Rone Charles, Brad Solomon, Jonathan P. Ling, Eddie Luidy Imada, David Zhang, Lance Joseph, Jeffrey T. Leek, Andrew E. Jaffe, Abhinav Nellore, Leonardo Collado-Torres, Kasper D. Hansen, Ben Langmead
Journal: Genome biology (2021)

We present recount3, a resource consisting of over 750,000 publicly available human and mouse RNA sequencing (RNA-seq) samples uniformly processed by our new Monorail analysis pipeline. To facilitate access to the data, we provide the recount3 and snapcount R/Bioconductor packages as well as complementary web resources. Using these tools, data can be downloaded as study-level summaries or queried for specific exon-exon junctions, genes, samples, or other features. Monorail can be used to process local and/or private data, allowing results to be directly compared to any study in recount3. Taken together, our tools help biologists maximize the utility of publicly available RNA-seq data, especially to improve their understanding of newly collected data. recount3 is available from http://rna.recount.bio .
A review of pregnancy-induced changes in opioid pharmacokinetics, placental transfer, and fetal exposure: Towards fetomaternal physiologically-based pharmacokinetic modeling to improve the treatment of neonatal opioid withdrawal syndrome
Authors: Matthijs W. van Hoogdalem, Scott L. Wexelblatt, Henry T. Akinbi, Alexander A. Vinks, Tomoyuki Mizuno
Journal: Pharmacology & Therapeutics (2021)
The IL-2/IL-15 Mimetic NL-201 Prevents Myeloma Relapse after ASCT By Expanding Highly Cytolytic T Cells in the Bone Marrow That Are Resistant to Exhaustion
Authors: Simone A Minnie, Nicole S Nemychenkov, Shuichiro Takahashi, Christine R Schmidt, Samuel RW Legg, Kathleen S Ensbey, Geoffrey R Hill
Journal: Blood (2021)
Abstract 14217: Myofibroblasts Enhance the Intrinsic Sinus Rhythm at Low Cell-Cell Coupling
Authors: Tae Kim, Jinqi Fan, Mingee Chung, Hee C Cho
Journal: Circulation (2021)

Heart rhythm is initiated by the sinoatrial node (SAN). Compared to the chamber myocardium, the healthy SAN exhibits an exceedingly high content of fibroblasts (FBs). Developmental, aging and pathophysiological cues can activate FBs to myofibroblasts (MFBs) which exhibit depolarized membrane potential and stronger electrotonic coupling compared to FBs. We hypothesized that MFBs, at a low content, can paradoxically increase the pacing frequency of pacemaker cells (PMs) by contributing to the spontaneous depolarization slope.Monolayers and scaffold-free 3D spheroids of TBX18-induced PMs (iPMs) were generated as in vitro models of SAN by somatic gene transfer of TBX18 to neonatal rat cardiomyocytes. Retrograde-perfused, adult rat heart was employed to study intact SAN ex vivo. In silico modeling was performed to simulate pacing frequencies of PMs coupled to MFBs in 2D and 3D pacemaker tissues. Upon reducing electrotonic coupling with carbenoxolone (CBX, 5μM), pacing frequency of iPM monolayers either increased from 66 ± 51 to 168 ± 92 bpm (n=4/13) or decreased from 125 ± 47 to 98 ± 28 bpm (n=9/13). GFP-transduced control NRVM monolayers (n=8) showed only occasional activity, which was not affected by CBX treatment (|ΔBR| = 57 ± 69 in iPM monolayers vs. 11± 11 bpm in control, GFP monolayers, p&lt;0.05). In culture, FBs are known to undergo spontaneous activation to MFBs via TGFβ signaling. Treatment of iPM spheroids with a TGFβ inhibitor (SB431542, 10μM) slowed their automaticity to 124 ± 89 bpm compared to 214 ± 18 bpm in untreated iPM spheroids. Sinus rhythm of the rat heart ex vivo increased upon CBX treatment from 199 ± 64 to 242 ± 80 bpm (n=3, p=0.07). Immunostaining confirmed presence of αSMA+ MFBs in both iPMs and the SAN. Computational study demonstrated that pacing frequencies of 2D and 3D PMs rose and fell with increasing gap junction conductance when coupled to MFBs (Vrest = -25 mV, g = 0 to 4.0 nS) but not to FBs (Vrest = -50 mV, g = 0 to 0.4 nS). Dynamic range of cardiac pacing was optimal when the ratio of MFB to PM was no more than one.Our data demonstrate that MFBs positively contribute to the pacing frequency and the safety factor of the sinus rhythm. We identify fibroblast activation state as a potential target to rejuvenate heart rhythm under aging and pathological conditions.
Abstract 11648: Bleeding in Patients Receiving Inhaled Pulmonary Vasodilators for Heart Failure Operations
Authors: Erick D Lorenzana-Saldivar, Mary Cooter, Jhana Parikh, Carmelo A Milano, Jessica Poisson, Sudarshan Rajagopal, Jerrold Levy, Kamrouz Ghadimi
Journal: Circulation (2021)

Introduction: Inhaled pulmonary vasodilators (iPVD) are initiated after CPB during advanced HF operations to reduce RV failure development from high PVR. While inhaled nitric oxide (iNO) is the prototype, its high cost has led to inhaled epoprostenol (iEPO) use. While intravenous epoprostenol contributes to bleeding by platelet inhibition, bleeding and iEPO use has not been compared with iNO in this population. Hypothesis: No differences will be seen in perioperative bleeding between iEPO and iNO groups. Methods: A secondary analysis of a blinded RCT of 232 patients who underwent LVAD placement or orthotopic heart transplantation (HT), to receive either iEPO or iNO (NCT03081052). Bleeding outcomes were classified through POD 7 as blood product units transfused, delayed sternal closure for bleeding, need for re-exploration due to bleeding/tamponade, and chest tube output volume 12-hours immediately after surgery. Three-level ordinal primary outcome for bleeding was determined and compared between groups via univariable and multivariable proportional odds models. A priori bleeding risk factors were used to adjust for a multivariable model. RBC units transfused were compared univariably by negative binomial regression modeling. Results: Of 232 patients, 220 met inclusion criteria: 113 (51%) received iEPO and 107 (49%) received iNO. Of 220, 99 (45%) had LVAD placement while 121 (55%) had HT. Duration of use was similar between groups. Bleeding was common with mild-moderate bleeding in 49 % of the iEPO group v 46 % in iNO group, and severe-massive bleeding in 44% of iEPO group v 47% of iNO group. No differences for bleeding classes were seen in either univariable (OR 1.08, 95% CI: 0.65, 1.81) or multivariable (OR 1.14, 95% CI: 0.60, 2.17) proportional odds models. Modeling showed no differences in RBC transfusion between groups (mean ratio 1.16, 95% CI: 0.82, 1.64). Conclusion: No differences were seen in perioperative bleeding between iEPO v iNO for advanced HF operations.
Safety and disease flare of autoimmune inflammatory rheumatic diseases: a large real-world survey on inactivated COVID-19 vaccines
Authors: Yong Fan, Yan Geng, Yu Wang, Xuerong Deng, Guangtao Li, Juan Zhao, Lanlan Ji, Xiaohui Zhang, Zhibo Song, Haoze Zhang, Xiaoying Sun, Dai Gao, Wenhui Xie, Hong Huang, YanJie Hao, Zhuoli Zhang
Journal: Annals of the Rheumatic Diseases (2021)

<h3>BACKGROUND:</h3> Noninvasive ventilation (NIV) is increasingly used during ventilatory support. Neurally-adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation that can improve patient-ventilator interaction. We conducted a meta-analysis to compare patient-ventilator interaction and clinical outcomes between NAVA and pressure support ventilation (PSV) in adult subjects during NIV. <h3>METHODS:</h3> The PubMed, Cochrane Library, Web of Science, OpenGrey, and Embase databases were searched for appropriate clinical trials comparing NIV-NAVA with NIV-PSV for adult subjects. Comparisons of asynchrony index (AI), types of asynchrony, and clinical outcomes were pooled. <h3>RESULTS:</h3> Fifteen studies were included involving 615 subjects. AI was significantly lower in NAVA than PSV group (mean difference [MD] −14.70 [95% CI −23.20 to −6.19], <i>P</i> &lt; .001). Subgroup analysis grouped by exacerbation of COPD or non-COPD showed that the AI of NAVA was lower than PSV in COPD exacerbation (MD −14.56 [95% CI −21.04 to −8.09], <i>P</i> &lt; .001) and non-COPD (MD −3.02 [95% CI −4.44 to −1.61], <i>P</i> &lt; .001). Severe asynchrony was significantly lower in NAVA than in PSV (odds ratio 0.06 [95% CI 0.03–0.11], <i>P</i> &lt; .001). Inspiratory trigger delay in NAVA was significantly lower than PSV (MD −129.60 [95% CI −148.43 to −110.78], <i>P</i> &lt; .001). NAVA had longer ICU length of stay than PSV (MD 1.22 [95% CI 0.44–2.00], <i>P</i> = .002). Level of discomfort was significantly higher in NAVA group than PSV group (MD 0.62 [95% CI 0.02–1.21], <i>P</i> = .040). <h3>CONCLUSIONS:</h3> NAVA has advantages in ventilator-patient interaction compared to PSV in NIV. Further research is needed in order to estimate effects on clinical outcomes.
Combined immunotherapy with controlled interleukin-12 gene therapy and immune checkpoint blockade in recurrent glioblastoma: An open-label, multi-institutional phase I trial
Authors: E Antonio Chiocca, Arnold B Gelb, Clark C Chen, Ganesh Rao, David A Reardon, Patrick Y Wen, Wenya Linda Bi, Pierpaolo Peruzzi, Christina Amidei, Dan Triggs, Leah Seften, Grace Park, James Grant, Kyla Truman, Jill Y Buck, Nira Hadar, Nathan Demars, John Miao, Taylor Estupinan, John Loewy, Kamal Chadha, Joseph Tringali, Laurence Cooper, Rimas V Lukas
Journal: Neuro-Oncology (2021)

Abstract Background Veledimex (VDX)-regulatable interleukin-12 (IL-12) gene therapy in recurrent glioblastoma (rGBM) was reported to show tumor infiltration of CD8+ T cells, encouraging survival, but also up-regulation of immune checkpoint signaling, providing the rationale for a combination trial with immune checkpoint inhibition. Methods An open-label, multi-institutional, dose-escalation phase I trial in rGBM subjects (NCT03636477) accrued 21 subjects in 3 dose-escalating cohorts: (1) neoadjuvant then ongoing nivolumab (1mg/kg) and VDX (10 mg) (n = 3); (2) neoadjuvant then ongoing nivolumab (3 mg/kg) and VDX (10 mg) (n = 3); and (3) neoadjuvant then ongoing nivolumab (3 mg/kg) and VDX (20 mg) (n = 15). Nivolumab was administered 7 (±3) days before resection of the rGBM followed by peritumoral injection of IL-12 gene therapy. VDX was administered 3 hours before and then for 14 days after surgery. Nivolumab was administered every two weeks after surgery. Results Toxicities of the combination were comparable to IL-12 gene monotherapy and were predictable, dose-related, and reversible upon withholding doses of VDX and/or nivolumab. VDX plasma pharmacokinetics demonstrate a dose-response relationship with effective brain tumor tissue VDX penetration and production of IL-12. IL-12 levels in serum peaked in all subjects at about Day 3 after surgery. Tumor IFNγ increased in post-treatment biopsies. Median overall survival (mOS) for VDX 10 mg with nivolumab was 16.9 months and for all subjects was 9.8 months. Conclusion The safety of this combination immunotherapy was established and has led to an ongoing phase II clinical trial of immune checkpoint blockade with controlled IL-12 gene therapy (NCT04006119).