tbuckley/cabot-search huggingface dataset:
Abstract 16546: Pre-Pregnancy Body Mass Index and Risk of Peripartum Cardiomyopathy and Heart Failure in the Years Following Delivery
Authors: Yuliya Mints, Asya Lyass, Michelle D Schmiegelow, morten schou, Gunnar H Gislason, Mia N Christiansen, Lars Kober, Christian Torp-Pedersen, Charlotte Andersson
Journal: Circulation (2020)

Introduction: Peripartum cardiomyopathy (PPCM) is a form of systolic heart failure that occurs during pregnancy or in the early post-partum period. Obesity is known to be associated with other forms of heart failure in young adults, however it is unclear if it is also a risk factor for the development of PPCM. Objectives: To investigate the association of body mass index (BMI) with PPCM and heart failure in the years following childbirth. Methods: We conducted a retrospective review of pregnant women in the Danish National Patient Registry between 2004 - 2017. Baseline characteristics and other risk factors were obtained at the first prenatal visit (occurring at 8-11 weeks post-conception). Women were followed until the end of the study period, emigration, or death. Logistic regression was performed, adjusting for age as well as other known risk factors for PPCM. Cox proportional hazards analysis was used to assess the long-term risk of development of heart failure. Results: There were 403,820 pregnancies evaluated in 300,892 women, with an average age of 29 years. The average BMI was 24.4 kg/m2, with 21.6% classified as overweight (BMI 25 - 30 kg/m2) and 12.8% as obese (BMI &gt; 30 kg/m2). The rate of PPCM was 0.1 per 1,000 in normal weight and overweight groups, and 0.3 per 1,000 in the obese women. After adjustment for age, ethnicity, smoking status, gestational diabetes, and presence of preeclampsia, there was a statistically significant increased risk of the development of PPCM up to 6 months after childbirth in patients who had class I (odds ratio [OR] 2.25, 95% CI 1.08-4.68) but not class II/III obesity (OR 1.63, 95% CI 0.60-4.43). This elevated risk persisted during long term follow up, with hazard ratios of 2.43 (95% CI 1.55 - 3.80) in women with class I obesity and 3.20 (95% CI 1.93 - 5.30) in women with class II/III obesity. Conclusions: High early pregnancy BMI is associated with elevated risk of development of peripartum cardiomyopathy even after adjustment for traditional risk factors. This risk of heart failure persists for several years after childbirth.
Abstract 13168: Cardiac Magnetic Resonance Imaging in a Phase 2 Study of Rilonacept in Recurrent Pericarditis
Authors: Paul Cremer, David Lin, Saifullah Nasir, Sushil A Luis, Andrew Ertel, Allan L Klein, Anna Beutler, Fang Fang, John Paolini
Journal: Circulation (2020)

Introduction: The magnitude of pericardial delayed hyperenhancement (DHE) by cardiac magnetic resonance imaging (CMR) illustrates the severity of inflammation in pericarditis. We report exploratory CMR data from an open-label Phase 2 study of rilonacept (IL-1α/IL-1β inhibitor) in recurrent pericarditis (RP). Methods: Patients (pts) with idiopathic RP or post-pericardiotomy syndrome (PPS) enrolled in the study. A subset had CMR at baseline (BL) and final visit (FV, 6 mo). Pain (NRS) and inflammation (CRP) were also collected. CMR images were graded (none, mild, moderate, or severe DHE) by a central core lab blinded to clinical data. Results: Of 25 study pts, 11 had CMR at BL and FV; 6 active idiopathic RP, and 5 corticosteroid (CS)-dependent non-active RP (4 idiopathic, 1 PPS). At BL, DHE was severe (3), moderate (2), and none (1) in active RP pts and moderate (1) or mild/none (4) in CS-dependent pts (Figure 1). At FV, DHE was improved (2), resolved (2; one pt example in Figure C/D), or unchanged (2) in active RP pts and was improved (1), resolved (1), unchanged (2) or worsened from none to mild (1) in CS-dependent pts. DHE improvements were associated with decreased pain and CRP and occurred despite discontinuation of CS or reduction in dose level. One pt with severe DHE at baseline and mild DHE at FV experienced a recurrence ~8 weeks after rilonacept discontinuation and enrolled a second time with severe DHE; the patient had reduced CRP and pain NRS during both enrollments and ended the second enrollment with moderate DHE. Conclusions: Serial CMR demonstrated improvement in pericardial DHE after 6 mo of rilonacept treatment, consistent with clinical improvement, while corticosteroids were tapered/discontinued. Recurrence in one pt with incompletely resolved DHE after 6 months of rilonacept treatment could indicate that a longer treatment duration is warranted in patients with unresolved DHE. These preliminary results may inform future CMR-guided treatment studies in RP.
A rare cause of an 18F-FDG positron emission tomography-positive lung lesion: look for what was lost…
Authors: Ellen Adams, Nico Mollet, Patrick Dewachter, Lynn Decoster
Journal: Thorax (2021)

A 64-year-old former smoker presented with right flank pain of 1-month duration, minor haemoptysis and weight loss (10% over the past 12 months). His medical history was remarkable for atrial fibrillation, type 2 diabetes and laparoscopic cholecystectomy (CCE) with peroperative cholangiography for acute calculous cholecystitis 10 months earlier. CT of the chest demonstrated a 56×38 mm spiculated mass in the right costodiaphragmatic recess with transdiaphragmatic infiltration and possible invasion of liver segment 7 (figure 1A,B). Positron emission tomography (PET) revealed increased 18F-fludeoxyglucose uptake in the lesion (figure 1C), without evidence of locoregional or distant metastases, raising concern for malignancy. An ultrasound-guided transthoracic needle biopsy was performed. Pathological examination showed chronic inflammation and fibrosis but no malignant cells. The case was discussed at the multidisciplinary tumour board during which radiological imaging was reviewed. The radiologist now described the presence of multiple calcifications posterior to the right liver lobe, just below the diaphragm and adjacent to the presumed lung mass (figure 2A). MRI of the upper abdomen was …
Abstract #1086: Brain cancer stem cells as potential research and therapeutic target in treatment of Glioblastoma Multiforme (GBM)
Authors: jay sharma, Rubio Punzalan, mariam majdoub, natalie liles, karl kramberger, gabriel velazquez, nina taw, christina dimaggio, cristian sharma, michael sharma, shaleekha sharma
Journal: Cancer Research (2009)

Brain Cancer stem cells as potential research and therapeutic target in treatment of Glioblastoma Multiforme (GBM) Primary brain tumors account for less than 2% of all cancers in adults; however, they are often associated with neurologic morbidity and high mortality. Glioblastoma multiforme (GBM) is one of the most malignant forms of human brain cancer. Despite intensive treatment, the mean survival of GBM patients remains about 1 year. Recent cancer studies revealed that cancer tissues are pathologically heterogeneous and only a small population of cells has the specific ability to reinitiate cancer. This small cell population is called cancer stem cells (CSCs); in brain cancers these are known as brain cancer stem cells (BCSCs). The identification of BCSCs yielded new insights into chemo-and radioresistance, by which BCSCs can survive selectively and initiate recurrence. The current research focused on BCSCs as treatment targets by generating an in vivo model system that may contribute to the discovery of new therapeutic strategies. Glioblastoma multiforme (GBM) has been a focus of new therapy development in neurooncology because it is the most common primary brain tumor in adults. Standard-of-care therapy for newly diagnosed GBM includes surgical resection, radiotherapy, and temozolomide, administered both during and after radiotherapy. However, most patients develop tumor recurrence or progression after this multimodality treatment. Repeat resection and stereotactic radiosurgery upon recurrence may improve outcome only in selected patients. The generation of the working in vivo GBM model system has enabled us to test leading compounds and potential drug candidates for the treatment of GBM patients.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1086.
Potent ex vivo armed T cells using recombinant bispecific antibodies for adoptive immunotherapy with reduced cytokine release
Authors: Jeong A Park, Brian H Santich, Hong Xu, Lawrence G Lum, Nai-Kong V Cheung
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background T cell-based immunotherapies using chimeric antigen receptors (CAR) or bispecific antibodies (BsAb) have produced impressive responses in hematological malignancies. However, major hurdles remained, including cytokine release syndrome, neurotoxicity, on-target off-tumor effects, reliance on autologous T cells, and failure in most solid tumors. BsAb armed T cells offer a safe alternative. Methods We generated ex vivo armed T cells (EATs) using IgG-[L]-scFv-platformed BsAb, where the anti-CD3 (huOKT3) scFv was attached to the light chain of a tumor-binding IgG. BsAb density on EAT, in vitro cytotoxicity, cytokine release, in vivo trafficking into tumors, and their antitumor activities were evaluated in multiple cancer cell lines and patient-derived xenograft mouse models. The efficacy of EATs after cryopreservation was studied, and gamma delta (γδ) T cells were investigated as unrelated alternative effector T cells. Results The antitumor potency of BsAb armed T cells was substantially improved using the IgG-[L]-scFv BsAb platform. When compared with separate BsAb and T cell injection, EATs released less TNF-α, and infiltrated tumors faster, while achieving robust antitumor responses. The in vivo potency of EAT therapy depended on BsAb dose for arming, EAT cell number per injection, total number of EAT doses, and treatment schedule intensity. The antitumor efficacy of EATs was preserved following cryopreservation, and EATs using γδ T cells were safe and as effective as αβ T cell-EATs. Conclusions EATs exerted potent antitumor activities against a broad spectrum of human cancer targets with remarkable safety. The antitumor potency of EATs depended on BsAb dose, cell number and total dose, and schedule. EATs were equally effective after cryopreservation, and the feasibility of third-party γδ-EATs offered an alternative for autologous T cell sources.
Abstract 11623: Temporal Changes of Noninvasive Electrocardiographic Risk Factors for Sudden Cardiac Death in Post-Myocardial Infarction Patients With Preserved Ejection Fraction: Insights From The Preserve EF Study
Authors: Iosif Xenogiannis, Konstantinos Gatzoulis, Panayota Flevari, Ignatios Ikonomidis, Eustathios Iliodromitis, Konstantinos Trachanas, Konstantinos Vlachos, Petros Arsenos, Dimitris Tsiachris, Dimitrios Tousoulis, Emmanouil Brilakis, Dimitrios Alexopoulos
Journal: Circulation (2019)

Introduction: Several noninvasive risk factors (NIRFs) have been proposed for predicting the risk for sudden cardiac death in post-myocardial infarction (post-MI) patients. However, it remains unkn...
Abstract 16862: Culture of Cardiac Mesenchymal Cells (CMCs) at Physiologic Oxygen Tension Greatly Enhances Cell Retention <i>In Vivo</i> After Myocardial Infarction
Authors: Chandrashekhar Dasari, Robi Bolli, Asma Arshia, Amr Alkasir, Yiru Guo, Usman Ashraf, Qianhong Li
Journal: Circulation (2020)

A major obstacle to using cell therapy for heart failure is the poor survival of transplanted cells. We have found that CMCs (a promising type of reparative cells) grown at 5% O 2 (the physiologic O 2 tension in the heart) are more resistant to severe hypoxia in vitro than CMCs grown at 21% O 2 , but the survival of these cells in vivo is unknown. Thus, female mice subjected to a 60-min coronary occlusion and 30 days of reperfusion received 1x10 6 male CMCs cultured at 21% O 2 or 5% O 2 (21%O 2 CMCs or 5%O 2 CMCs) via echo-guided injection into the LV cavity. Quantitative real-time PCR for single copy of a Y-chromosome-specific Sry gene sequence was performed using genomic DNA isolated from heart (right ventricle [RV], risk region [RR] and non-risk region [NR] of LV), lung, liver, spleen and kidney 24 h or 7 days after cell administration (Figure). Compared with 21% O 2 CMCs, culture at 5% O 2 markedly increased cell retention in RR &gt; NR &gt; RV at 24 h and up to 7 days after CMC administration (Figs. C-D). At 24 h, although 25% of all transplanted cells were present in the liver (Fig. E), the number of Sry + cells per mg of tissue was strikingly greater in RR (2131±248) &gt; NR (1447±250) &gt; RV (1047±156) compared with liver (274±131, P &lt;0.01) and kidney (619±140, P &lt;0.05) (n=6/group). These differences persisted up to 7 days (820±156 in RR, 667±156 in NR, 327±33 in RV vs. 103±45 in liver, P &lt;0.01; 179±50 in kidney, P &lt;0.05) (n=4-5/group). In summary, we provide a systematic, time-dependent, and highly quantitative analysis of cell retention and distribution after infusion of CMCs into the LV cavity of failing hearts. The results demonstrate that, compared with 21% O 2 , physiologic 5% O 2 tension greatly enhances the retention of CMCs in the heart at 24 h and 7 days after cell transplantation, especially in the scarred regions where O 2 is very low (1-2%). Thus, culture at 5% O 2 may improve the reparative properties of CMCs (and possibly other cell types) used for cell therapy, providing an approach that may be applicable in the clinic.
When visitors return to the wards: “You’re welcome . . . anytime”
Authors: Mary Lawson
Journal: BMJ (2021)

Clinicians’ experiences inform my work in medical education. Oliver’s suggestions for post-covid hospital visiting restrictions, allowing clinicians uninterrupted space to do their best work, made me pause for thought.1 Workplace stress for my clinical colleagues is enormous, but we need to question our responses and have them questioned by others.

Covid-19 has made students anxious and uncertain about clinical exposure and developing competence. Already feeling starved of “hands-on” experience, they are eager to develop their expertise, and Oliver’s suggestion would influence that.

Abused patients need …
Abstract 16542: Hypotension and Pericardial Effusion Associated With High Frequency Jet Ventilation
Authors: Patricia Tung, Jonathan W Waks, Alfred E Buxton
Journal: Circulation (2020)

Introduction: High frequency jet ventilation (HFJV) is used to increase catheter stability and improve outcomes during pulmonary vein isolation (PVI) [1,2,4]. In studies, hemodynamic intolerance of HFJV was rare. [1,3]. Hypothesis: HFJV during PVI is well tolerated and vasopressor-resistant hypotension requiring return to conventional ventilation is rare. Methods: Retrospective observational analysis of hemodynamic, blood gas, and echocardiographic data of PVIs performed with HFJV by 2 operators (PT, JW) at our institution between February 2019 and June 2020. Results: Among 193 PVIs, 8 cases (4%) of rapid onset hypotension associated with HFJV were found (Table). In 7 of 8 cases, persistent hypotension and abnormal gas exchange required conversion to conventional ventilation and a new, small pericardial effusion without tamponade was noted just after HFJV initiation. In these cases, initiation of HFJV was associated with a decrease in systolic function. Both the hemodynamic changes and effusion resolved completely within minutes of stopping HFJV. Four of 8 patients were rechallenged with HFJV, and had recurrent hypotension and effusion which resolved immediately after return to conventional ventilation. Conclusions: HFJV-associated rapid onset hypotension, often accompanied by transient pericardial effusion, is more common than previously reported, and resolves with cessation of HFJV. The mechanism of these changes may occur via CO2 levels and warrants further study.
LBA2 Impact of RNA expression signatures and tumour infiltrating lymphocytes (TILs) for pathological complete response (pCR) and survival after 12 week de-escalated neoadjuvant pertuzumab + trastuzumab ± paclitaxel in the WSG-HER2+/HR- ADAPT trial
Authors: M. Graeser, O. Gluz, C. Biehl, D. Ulbrich-Gebauer, J. Palatty, M. Christgen, S. Kuemmel, E-M. Grischke, D. Augustin, M. Braun, J. Potenberg, R. Wuerstlein, C. Eulenburg, R. Kates, C. Kolberg-Liedtke, F. Feuerhake, H. Kreipe, U. Nitz, N. Harbeck
Journal: Annals of Oncology (2021)
Abstract 13173: Unusual Fatigue and Failure to Utilize Emergency Medical Services Are Associated With Prolonged Prehospital Delay for Suspected Acute Coronary Syndrome
Authors: Holli A Devon, Mohamud R Daya, Elizabeth Knight, Mary-Lynn Brecht, Erica Su, Jessica K Zegre-hemsey, Sahereh Mirzaei, Stephanie O Frisch, Mary Mooney, Anne G Rosenfeld
Journal: Circulation (2020)

Introduction: Rapid reperfusion reduces infarct size and mortality for acute coronary syndrome (ACS) but efficacy is time dependent. Time to presentation in the Emergency Department (ED) remains excessive and patient-controlled prehospital delay may be a modifiable variable for intervention. The aim of the study was to determine if transportation factors and clinical presentation predicted prehospital delay for suspected ACS stratified by final diagnosis (ACS vs. no ACS). Hypothesis: Symptoms other than chest pain would contribute to longer prehospital delay that would vary by final diagnosis. Methods: Secondary analysis of data collected from a multi-center prospective study. A heterogeneous sample of ED patients with symptoms suggestive of ACS were enrolled at five sites in the US. Accelerated failure time (AFT) models were used to specify a direct relationship between delay time and variables to predict prehospital delay by final diagnosis. Results: The sample of 975 adults included 609 (62.5%) men and 366 (37.5%) women who were predominantly Caucasian (69.1%), had a mean age of 60.32 (±14.07) years, and had lower income levels (66.4% ≤$50,000 annually). Median delay time was 6.68 (1.91, 24.94) hours and only 26.2% had a prehospital delay of 2 hours or less. Patients with and without ACS presenting with unusual fatigue (TR=1.71, p=0.002; TR=1.54, p=0.003 , respectively) or self-transporting to the ED experienced significantly longer prehospital delay (TR 1.93, p&lt;0.001; TR 1.71, p&lt;0.001 , respectively). Predictors of shorter delay in patients with ACS were shoulder pain and lightheadedness (TR=0.65, p =0.013 and TR=0.67, p =0.022, respectively). Predictors of shorter delay for patients ruled-out for ACS were the presence of chest pain, sweating (TR=0.071, p =0.025 and TR=0.073, p =0.032, respectively). Conclusion: Patients self-transporting to the ED had prolonged prehospital delays. Encouraging the use of EMS is an important modifiable factor for patients with symptoms concerning for ACS. Calling 911 can be positively framed to at risk patients and the community as having advanced care come to them since EMS diagnostic capabilities include 12-lead ECG acquisition and possibly high sensitivity troponin assays.
Abstract 17448: Comprehensive Characterization of Alternative Polyadenylation in Human Right Ventricle Failure
Authors: Rajarajan Amirthalingam Thandavarayan, Scott D Collum, Keith Youker, Rajaseakaran Mahalingam, Leng Han, Eric J Waganer, Arvind Bhimaraj, Harry Karmouty-quintana, Ashrith Guha
Journal: Circulation (2020)

Background: Alternative cleavage and polyadenylation (APA) an emerging post-transcriptional mechanism for gene regulation that generates distinct isoforms of mRNA with different 3’UTR lengths. APA plays an important role in different biological processes and dysregulation of APA leading to many human diseases. However, the functional consequences of APA events in the right ventricle (RV) failure in humans remain unexplored. Objective: To identify whether the 3′UTR length is modulated by APA in the RV failure in humans compared to healthy RV. Methods and Results: We used Poly A tail RNA sequencing and a novel algorithm called DaPars to measure the global patterns of APA in healthy and failing human RV specimens. We revealed 3'UTR shortening and lengthening of many genes in failing RV compared to healthy RV specimens. The lengthened 3’UTR genes were enriched for functional groups such as RNA processing and splicing. Whereas the shortened 3’UTR genes were enriched for nucleic acid metabolic process and chromatin organization. In addition, differential APA events in RV failure regulates many pathways important for the progression of the RV failure. Finally, the regulator proteins of APA including cleavage and polyadenylation specificity factor (CPSF) 6 and 7, cleavage factor Im (CFIm) 25 and 59 have been regulated in RV failure compared to healthy RV specimens. Conclusions: Our results highlight important roles of APA in the progression of RV failure in humans, including RNA processing, splicing, and specific gene expression. Demonstrating that APA mediated 3’UTR length regulation provides the additional layer of gene expressions in RV failure.
Covid-19: Most UK adults had antibodies after one dose of AstraZeneca or Pfizer vaccine, data suggest
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Covid-19: Most UK adults had antibodies after one dose of AstraZeneca or Pfizer vaccine, data suggest Gareth IacobucciMore than nine in 10 UK adults have antibodies to SARS-CoV-2 following one dose of the Oxford AstraZeneca or Pfizer BioNTech vaccine, while almost everyone does after a second dose, preliminary data suggest. 1 1
Abstract 12992: LA Strain Predicts Exercise Capacity in Chronic Kidney Disease
Authors: Gary Gan, Aditya Bhat, Henry H.L. Chen, Kennith Gu, Fernando Fernandez, Karen Byth, Suzanne Eshoo, Krishna K Kadappu, Liza Thomas
Journal: Circulation (2020)

Background: Left atrial (LA) function plays a pivotal role in modulating left ventricular performance particularly during exercise. The aim of our study was to evaluate the relationship between resting LA function by strain analysis as a determinant of exercise capacity in chronic kidney disease (CKD) patients, and evaluate its utility compared to exercise E/e’. Methods: Consecutive Stage 3 and 4 CKD patients without prior cardiac history were prospectively recruited from outpatient nephrology clinics and underwent clinical evaluation, resting and exercise stress echocardiography. Patients needed to be in sinus rhythm without significant valvular disease or ischaemia on stress testing. Resting echocardiographic parameters including E/e’ and phasic LA strain [LA reservoir (LASr), conduit (LAScd) and contractile (LASct) strain] were measured and compared to exercise E/e’. Results: 218 (63.9±11.7yrs, 64% men) CKD patients were recruited. Independent clinical predictors of exercise capacity were age, eGFR, body mass index and gender (p&lt;0.01 for all) while independent resting echocardiographic predictors included E/e’, LASr and LASct (p&lt;0.01 for all). Amongst independent resting echocardiographic predictors, LASr ( r =0.70,p&lt;0.01) demonstrated the strongest correlation to METs achieved. Receiver operating characteristic curves (Figure 1) demonstrated that LASr (AUC 0.83,) had similar predictive value as exercise E/e’ (AUC 0.79; AUC difference of 0.05, p=0.20 on DeLong test). A model combining LASr and clinical metrics showed robust predictive capacity for METs achieved in CKD patients. Conclusions: LASr, a marker of decreased LA compliance is an independent predictor of exercise capacity in Stage 3 and 4 CKD patients, with similar predictive value to exercise E/e’. The use of LASr may serve as a resting biomarker of functional capacity in this population.
Flow-Mediated Vasodilation Is restored in Corkscrew Collaterals in Patients with Thromboangitis Obliterans
Authors: Fujii Yuichi, Higashi Yukihito, Hidaka Takayuki, Hata Takaki, Zushi Naomi, Fujimura Noritaka, Mikami Shinsuke, Maruhashi Tatsuya, Kihara Yasuki
Journal: Circulation (2012)