tbuckley/cabot-search huggingface dataset:
Abstract 17132: Atrial Fibrillation Ablation in Heart Failure: Temporal Trends and Outcomes in Hospitalized Patients
Authors: Manyoo Agarwal, Brijesh Patel, Lohit Garg, Mahek Shah, Rami Khouzam, Rajesh Kabra
Journal: Circulation (2018)

Introduction: Recent studies have shown catheter ablation for atrial fibrillation (AF) in patients with heart failure (HF) to have better outcomes over medical therapy. While AF ablation is predominantly an outpatient procedure, some patients may require longer hospitalization. Limited literature exists describing the trends of hospitalizations for HF patients undergoing AF ablation. Methods: Using ICD-9 (diagnosis and procedure codes) in nationwide inpatient sample database 2003 to 2014, we identified all HF adults who were admitted with a principal diagnosis code of AF (427.31) (n= 4,670,400) (AF-HF). Among these, we identified those with a principal procedure code of catheter ablation (37.34) and studied the temporal trends of clinical characteristics and outcomes (in-hospital mortality and complications) for this cohort (Table). Results: The overall number of AF-HF patients undergoing AF ablation was 62,653; with an increase from 1,928 in 2003 to 6,860 in 2014 (p trend&lt;0.001). As shown in Table, over this 12-year period; mean age and proportion of females decreased, while there was an increase in blacks, clinical comorbidity burden, admissions to teaching hospitals and southern US region (all p trend&lt;0.001). The overall procedure related complications (vascular, cardiac, respiratory, neurologic) increased, the in-hospital mortality rate decreased from 1.7% to 0.5% (all p trend&lt;0.001). Conclusions: During 2003-2014, the annual incidence of AF ablation related hospitalizations in HF patients increased significantly. Despite increase in clinical comorbidities burden and procedural complication rates, the mortality rate declined.
The fight against stroke must go on
Authors: None The Lancet Neurology
Journal: The Lancet Neurology (2020)

Rio de Janeiro, Brazil, recently hosted what will probably be one of the last in-person neurology conferences for some time. The first Global Stroke Alliance meeting, held on March 11–13, 2020, ended a day early because of the COVID-19 pandemic, and many participants could join only remotely as travel became restricted. Nonetheless, participants heard about several promising initiatives to prevent and treat stroke in Latin America and across the world. A few weeks on, preventing stroke and improving stroke care seem even more challenging than before COVID-19, but these goals remain crucial if we are to reduce the global burden of stroke and ensure that stroke services are resilient in difficult times.
Genomic Perspectives on the Emerging SARS-CoV-2 Omicron Variant
Authors: Wentai Ma, Jing Yang, Haoyi Fu, Chao Su, Caixia Yu, Qihui Wang, Ana Tereza Ribeiro de Vasconcelos, Georgii A. Bazykin, Yiming Bao, Mingkun Li
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract A new variant of concern for SARS-CoV-2, Omicron (B.1.1.529), was designated by the World Health Organization on November 26, 2021. This study analyzed the viral genome sequencing data of 108 samples collected from patients infected with Omicron. First, we found that the enrichment efficiency of viral nucleic acids was reduced due to mutations in the region where the primers anneal to. Second, the Omicron variant possesses an excessive number of mutations compared to other variants circulating at the same time (median: 62 vs. 45), especially in the Spike gene. Mutations in the Spike gene confer alterations in 32 amino acid residues, more than those observed in other SARS-CoV-2 variants. Moreover, a large number of nonsynonymous mutations occur in the codons for the amino acid residues located on the surface of the Spike protein, which could potentially affect the replication, infectivity, and antigenicity of SARS-CoV-2. Third, there are 53 mutations between the Omicron variant and its closest sequences available in public databases. Many of these mutations were rarely observed in public databases and had a low mutation rate. In addition, the linkage disequilibrium between these mutations was low, with a limited number of mutations concurrently observed in the same genome, suggesting that the Omicron variant would be in a different evolutionary branch from the currently prevalent variants. To improve our ability to detect and track the source of new variants rapidly, it is imperative to further strengthen genomic surveillance and data sharing globally in a timely manner.
Dental stem cell-derived extracellular vesicles as promising therapeutic agents in the treatment of diseases
Authors: Ye Li, Xu Duan, Yinxue Chen, Bingyun Liu, Gang Chen
Journal: International Journal of Oral Science (2022)

Abstract Dental stem cells (DSCs), an important source of mesenchymal stem cells (MSCs), can be easily obtained by minimally invasive procedures and have been used for the treatment of various diseases. Classic paradigm attributed the mechanism of their therapeutic action to direct cell differentiation after targeted migration, while contemporary insights into indirect paracrine effect opened new avenues for the mystery of their actual low engraftment and differentiation ability in vivo. As critical paracrine effectors, DSC-derived extracellular vesicles (DSC-EVs) are being increasingly linked to the positive effects of DSCs by an evolving body of in vivo studies. Carrying bioactive contents and presenting therapeutic potential in certain diseases, DSC-EVs have been introduced as promising treatments. Here, we systematically review the latest in vivo evidence that supports the therapeutic effects of DSC-EVs with mechanistic studies. In addition, current challenges and future directions for the clinical translation of DSC-EVs are also highlighted to call for more attentions to the (I) distinguishing features of DSC-EVs compared with other types of MSC-EVs, (II) heterogeneity among different subtypes of DSC-derived EVs, (III) action modes of DSC-EVs, (IV) standardization for eligible DSC-EVs and (V) safety guarantee for the clinical application of DSC-EVs. The present review would provide valuable insights into the emerging opportunities of DSC-EVs in future clinical applications.
A prospective phase II study of biweekly S-1, leucovorin and gemcitabine in elderly patients with locally advanced or metastatic pancreatic adenocarcinoma.
Authors: Li-Yuan Bai, Chung-Pin Li, Yan-Shen Shan, Shih-Chang Chuang, Jen-Shi Chen, Nai-Jung Chiang, Yen-Yang Chen, Hsiao-Hui Tsou, Mei-Hsing Chuang, Chang-Fang Chiu, Tsang-Wu Liu, Li-Tzong Chen
Journal: Journal of Clinical Oncology (2022)

550 Background: A chemotherapeutic regimen for elderly patients with advanced pancreatic cancer is necessary because of the considerable toxicities associated with current standard regimens. A modified combination of gemcitabine, S-1, and leucovorin (GSL) was used as a first-line treatment for elderly patients with newly diagnosed locally advanced or metastatic pancreatic adenocarcinoma in a prospective, phase II, multicenter clinical trial (NCT03559348). Methods: Patients more than 70 years of age with ECOG performance status score 0-2 were treated with GSL. GSL was administered every 2 weeks, intravenous gemcitabine 800 mg/m 2 at a fixed-dose rate of 10 mg/m 2 /min on day 1 and oral S-1 (80-120 mg/day) plus leucovorin 30 mg twice daily on days 1-7, until disease progression, withdrawal, or intolerable toxicities. The primary endpoint was progression-free survival (PFS). Results: Overall, 49 patients were enrolled into the trial between 10 July, 2018 and 25 March, 2020, with a median follow-up of 12.5 months. The data cut-off point was on 15 June, 2021. The median patient age at diagnosis was 76 years (range, 70–87 years), and thirty-two (65.3%) patients had metastatic lesions before GSL treatment. Patient frailty was evidenced by the Vulnerable Elders Survey (VES)-13 score (median 5, range 0-13) and Geriatric 8 (G8) score (median 10.5, range 3-15) at baseline. Among the 44 evaluable patients, 13 demonstrated a partial response (29.5%) and 24 presented with stable disease (54.5%). The median PFS was 6.6, 6.6, and 6.3 months, and OS was 12.5, 12.7, and 11.6 months for total population, patients with locally advanced disease, and patients with metastatic lesions, respectively. Patients had improved emotional function and global health status score during GSL treatment. The most frequent grade 3 or higher treatment-related toxicities included anemia (20.4%), decreased neutrophils (18.4%), decreased white blood cells (16.3%), and oral mucositis (12.2%). Conclusions: The GSL regimen results in impressive efficacy with tolerable toxicity in this group of frail patients. In addition, quality of life can be maintained during the treatment. GSL could be a treatment of choice for elderly patients with locally advanced or metastatic pancreatic cancer. Clinical trial information: NCT03559348.
Abstract 17020: Exercise With or Without Weight Loss and Functional Decline in Overweight or Obese Adults With Peripheral Artery Disease
Authors: Tamar S Polonsky, Dongxue Zhang, Lydia A Bazzanno, Michael H Criqui, Luigi Ferrucci, Jack M Guralnik, Melina Kibbe, Robert L Sufit, Mary M McDermott
Journal: Circulation (2018)

Background: Overweight or obese adults with PAD have greater functional decline than normal-weight adults with PAD. Walking exercise is first-line therapy for PAD. It is unknown whether weight loss+exercise is associated with less functional decline than exercise alone. Weight loss could worsen functional decline by decreasing muscle mass. Methods: Adults with PAD (ABI &lt;0.90) and BMI ≥25 kg/m 2 underwent baseline testing 2002-2004. Mean follow-up was 3.4 years. Weight, six minute walk distance (6MWD) and self-reported exercise were measured annually. Weight loss was defined as ≥5 lb decrease compared to the prior year. Exercise was defined as walking ≥3 times/week for ≥30 min. To compare annual changes in 6MWD between groups (no exercise, exercise only, or exercise+weight loss) a mixed-effects linear regression analysis was used with a subject-specific random intercept, to account for the chance that a person’s annual change in 6MWD correlated with the prior annual change. Person-years for each group were summed from successive annual changes; adults could contribute person-years to ≥1 group. Analyses were adjusted for age, race, sex, ABI, smoking, comorbidities, lower extremity revascularization or hip/knee replacement during follow-up. Results: Among 271 adults (41% women, 15% black), mean age was 74±7.6 and ABI was 0.64±0.15. Mean baseline BMI was similar across groups (no exercise 30.7±4.6 kg/m 2 ; exercise only 28.8±3.5 kg/m 2 ; exercise+weight loss 30.1±4.3 kg/m 2 ). PAD participants who walked for exercise and lost weight had less decline in 6MWD than those who walked without weight loss, or who neither exercised nor lost weight (p trend = 0.004) (Table). Conclusions: Overweight and obese adults with PAD who exercised and lost ≥5 lbs experienced less annual decline in the 6MWD than adults with only exercise or no exercise. A randomized trial is needed to determine whether weight loss+exercise improves functional outcomes for overweight or obese adults with PAD.
Prognostic Role of Echocardiographic Parameters in Heart Failure Patients with Incidental Massive Pleural Effusion Diagnosed During Echocardiographic Evaluation
Authors: Süleyman Ercan, Vedat Davutoğlu, Muhammed Oylumlu, İbrahim Halil İnanç, Mehmet Kaplan
Journal: Journal of the American College of Cardiology (2013)
Abstract P249: Hemostatic Factors and Long-Term Risk of Peripheral Arterial Disease: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Aozhou Wu, Shoshana H Ballew, Corey A Kalbaugh, Laura R Loehr, Anna Kucharska-Newton, Ron C Hoogeveen, Christie M Ballantyne, Gerardo Heiss, Aaron R Folsom, Josef Coresh, Kunihiro Matsushita
Journal: Circulation (2017)

Background: A few cross-sectional studies have reported associations between hemostatic factors and peripheral arterial disease (PAD), but prospective data are largely lacking. Hypothesis: Plasma hemostatic factors are associated with incident PAD, independently of traditional atherosclerotic risk factors. Methods: In 14,071 men and women (age 45-64 years and 25.4% blacks) at visit 1 (1987-1989) of the ARIC Study, we investigated the associations of fibrinogen, Von Willebrand factor (VWF), factor VIII, factor VII, Antithrombin III (ATIII) with incidence of PAD (defined as hospitalizations with PAD diagnosis [ICD-9: 440.2x, 440.3, and 440.4] or leg revascularization [38.18, 39.25, 39.29 and 39.50]). We also explored associations of d-dimer measured at visit 3 (1993-1995) in 11,619 participants. Results: We identified 540 incident PAD during a median follow-up of 24.4 years. Fibrinogen, VWF, factor VIII, and d-dimer demonstrated positive dose-response relationships to incident PAD, independent of other risk factors (Table). In comparison with respective referent categories, significantly higher PAD risk was observed in the top two quintiles of fibrinogen, VWF, and d-dimer and the highest quintile of factor VIII. When fibrinogen, VWF, and factor VIII were modeled simultaneously (d-dimer was measured at a different visit), only fibrinogen and VWF remained significantly associated with PAD. Conclusion: Hemostatic factors, particularly fibrinogen and VWF (as well as d-dimer), were independently associated with future risk of PAD. Our findings suggest the pathophysiological involvement of hemostasis in the development of PAD and potential usefulness of those factors for classifying long-term risk of PAD.
A large unselected series of consecutive OPCAB patients demonstrates reduced hospital morbidity and mortality Mark W. Connolly, Valavanur A. Subramanian, Nilesh U. Patel, John C. McCabe, Mark H. Genovesi, Didier F. Loulmet, Rita M. Considine, Archana Maini. Lenox Hill Hospital, New York, NY
Journal: Journal of the American College of Cardiology (2001)
CLK2 upregulation and outcomes for males with colorectal adenocarcinoma.
Authors: Zain I. Siddiqui, Chenyu Sun, John Pocholo W. Tuason, Jannell F. Lising, Arpana Paudel, Marwan K. Ahmed, Na Hyun Kim, Chandur Bhan, Burhan Memon, Humaed Mohammed Abdul, Apurwa Prasad
Journal: Journal of Clinical Oncology (2022)

159 Background: Colorectal adenocarcinoma (COAD) is a common cancer in gastrointestinal tract. CDC-like kinase (CLK) family, containing four characterized isoforms (CLK1-4), have been reported for their roles in precursor-mRNA splicing. However, studies on their roles in COAD are limited. Thus, this study was performed to explore the roles of CLK family members in COAD. Methods: RNA-sequencing FPKM data and corresponding clinical information of 41 normal tissues and 480 tumor tissues of COAD were obtained from The Cancer Genome Atlas (TCGA). Then expression differences of CLK family between the normal tissues and COAD cancer tissues were compared with Wilcoxon rank-sum test via ‘limma’ package. Overall survival (OS) of upregulated CLK family members was analyzed by Kaplan–Meier (K–M) method via ‘survminer’ package. Subgroup analyses of different genders were also conducted. The best discriminate cut-off point between the high and low expression groups was assessed by the receiver operating characteristic (ROC) curve and area under the curve (AUC) values for upregulated CLK family members via ‘pROC’ package to assess their diagnostic values. Results: The expression of CLK1 and CLK2 were upregulated in tumors compared with normal tissues (p &lt; 0.001), while CLK3 were downregulated in tumor tissues (p = 0.02) and no statically significant difference was found regarding CLK4 (p = 0.25). Higher expression of CLK1 was not associated with a change of OS (HR: 1.24, 95%CI: 0.84-1.83, p = 0.279), while higher expression of CLK2 is associated with worse OS (HR: 2.03, 95%CI: 1.34-3.06, p = 0.001). Subgroup analysis found that higher expression of CLK2 was associated with worse OS (HR: 2.28, 95%CI 1.27-4.08, p = 0.006) in males, but not in females (HR: 1.72, 95%CI 0.95-3.10, P = 0.072). Further analysis of ROC curve shown that AUC of CLK1 and CLK2 were 0.748 (0.687-0.809) and 0.884 (0.840-0.928), respectively. Conclusions: CLK1 and CLK2 are upregulated in COAD tumor samples, and higher expression of CLK2 in male COAD patients is associated worse OS. This demonstrated the potential therapeutic value of CLK2 in male patients with COAD. ROC curve indicated the potential diagnostic value of CLK1 and CLK2.
Liquid Biopsy: It's the Bloody Truth!
Authors: Nathan M. Hawkey, Andrew J. Armstrong
Journal: Clinical Cancer Research (2021)

Abstract Liquid biopsy is a promising clinical tool that can provide critical information for prognostication and which may inform treatment decisions in men with metastatic castration-resistant prostate cancer. Here we discuss the Foundation Medicine plasma cell-free circulating tumor DNA assay, its pros and cons, and potential clinical utility. See related article by Tukachinsky et al., p. 3094
Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma.
Authors: Gregory P. Botta, Maen Abdelrahim, Vasily N. Aushev, Abdullah Esmail, Bridgette Drummond, Shruti Sharma, Ekaterina Kalashnikova, Nicole Hook, Sreenivasa R Chandana, Mohamedtaki Abdulaziz Tejani, Midhun Malla, Liudmila N. Schafer, Pashtoon Murtaza Kasi, Giby V. George, Alexey Aleshin, Farshid Dayyani, Diana L. Hanna
Journal: Journal of Clinical Oncology (2022)

517 Background: Pancreatic adenocarcinoma (PDAC) is the third leading cause of cancer-related death, with a recurrence rate of 85% after curative surgery and a 5-year survival rate of 10%. Serum biomarkers like CA 19-9 lack sensitivity and specificity (10% of patients fail to produce CA 19-9), and are poor indicators of molecular residual disease (MRD). Circulating tumor DNA (ctDNA) detection allows for MRD identification months ahead of radiological findings, and may assess molecular response and patient outcomes. Methods: A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for the detection and quantification of ctDNA in a prospective clinical cohort of patients. Serial time points were collected for unresectable, borderline resectable, and resectable subsets of patients to monitor ctDNA levels in response to treatment (see Table). Results: 93 patients were included, with a median age of 67.3 yrs and 45% female. 285 timepoints were analyzed for ctDNA presence, with each patient having between 1 and 7 timepoints (median 3 timepoints per patient). 46 patients had one or more samples positive for ctDNA, resulting in an anytime ctDNA positivity rate of 49.5%. Anytime positivity correlated with the stage of disease (p&lt;0.001). Within ctDNA-positive samples, observed levels were 0.04-1227 mean tumor molecules per mL of plasma (mean 35.1, median 1.02 MTM/mL). During the follow-up period (median 13.5 months, range 1-80 months), 36 patients had recurrence or disease progression events. Recurrence-free survival (RFS) strongly correlated with post-operative anytime ctDNA positivity: Hazards Ratio 8.0 (95% CI 3.4-18.7), p =1.6e-6. For 49 patients, CA 19-9 measurements were available. Elevated CA 19-9 was not correlated with RFS (p=0.35). Conclusions: Our study demonstrates the feasibility of tumor-informed ctDNA-based MRD testing in PDAC, in 93 patients of all stages. ctDNA positivity correlated with patient survival outcomes more strongly than CA19-9. Our data suggests patients can benefit from personalized and tumor-informed MRD testing.[Table: see text]
Response to: ‘Correspondence on ‘Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician reported registry’’ by Rosenbaum<i>et al</i>
Authors: Kimme L Hyrich, Martin Schäfer, Anja Strangfeld, Loreto Carmona, Laure Gossec, Elsa F Mateus, Saskia Lawson-Tovey, Milena Gianfrancesco, Philip C Robinson, Jinoos Yazdany, Pedro M Machado
Journal: Annals of the Rheumatic Diseases (2021)

<h3>Objective</h3> To investigate how electronic templates shape, enable and constrain consultations about chronic diseases. <h3>Design</h3> Ethnographic case study, combining field notes, video-recording, screen capture with a microanalysis of talk, body language and data entry—an approach called linguistic ethnography. <h3>Setting</h3> Two general practices in England. <h3>Participants and methods</h3> Ethnographic observation of administrative areas and 36 nurse-led consultations was done. Twenty-four consultations were directly observed and 12 consultations were video-recorded alongside computer screen capture. Consultations were transcribed using conversation analysis conventions, with notes on body language and the electronic record. The analysis involved repeated rounds of viewing video, annotating field notes, transcription and microanalysis to identify themes. The data was interpreted using discourse analysis, with attention to the sociotechnical theory. <h3>Results</h3> Consultations centred explicitly or implicitly on evidence-based protocols inscribed in templates. Templates did not simply identify tasks for completion, but contributed to defining what chronic diseases were, how care was being delivered and what it meant to be a patient or professional in this context. Patients’ stories morphed into data bytes; the particular became generalised; the complex was made discrete, simple and manageable; and uncertainty became categorised and contained. Many consultations resembled bureaucratic encounters, primarily oriented to completing data fields. We identified a tension, sharpened by the template, between different framings of the patient—as ‘individual’ or as ‘one of a population’. Some clinicians overcame this tension, responding creatively to prompts within a dialogue constructed around the patient9s narrative. <h3>Conclusions</h3> Despite their widespread implementation, little previous research has examined how templates are actually used in practice. Templates do not simply document the tasks of chronic disease management but profoundly change the nature of this work. Designed to assure standards of ‘quality’ care they contribute to bureaucratisation of care and may marginalise aspects of quality care which lie beyond their focus. Creative work is required to avoid privileging ‘institution-centred’ care over patient-centred care.
Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring
Authors: Wen Li, Ji-Bin Liu, Li-Kun Hou, Fei Yu, Jie Zhang, Wei Wu, Xiao-Mei Tang, Feng Sun, Hai-Min Lu, Jing Deng, Jie Bai, Juan Li, Chun-Yan Wu, Qin-Lu Lin, Zhong-Wei Lv, Gao-Ren Wang, Geng-Xi Jiang, Yu-Shui Ma, Da Fu
Journal: Molecular Cancer (2022)

Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.