tbuckley/cabot-search huggingface dataset:
Clinical Management of Stable Coronary Artery Disease in Patients With Type 2 Diabetes Mellitus: A Scientific Statement From the American Heart Association
Authors: Suzanne V. Arnold, Deepak L. Bhatt, Gregory W. Barsness, Alexis L. Beatty, Prakash C. Deedwania, Silvio E. Inzucchi, Mikhail Kosiborod, Lawrence A. Leiter, Kasia J. Lipska, Jonathan D. Newman, Francine K. Welty
Journal: Circulation (2020)

Although cardiologists have long treated patients with coronary artery disease (CAD) and concomitant type 2 diabetes mellitus (T2DM), T2DM has traditionally been considered just a comorbidity that affected the development and progression of the disease. Over the past decade, a number of factors have shifted that have forced the cardiology community to reconsider the role of T2DM in CAD. First, in addition to being associated with increased cardiovascular risk, T2DM has the potential to affect a number of treatment choices for CAD. In this document, we discuss the role that T2DM has in the selection of testing for CAD, in medical management (both secondary prevention strategies and treatment of stable angina), and in the selection of revascularization strategy. Second, although glycemic control has been recommended as a part of comprehensive risk factor management in patients with CAD, there is mounting evidence that the mechanism by which glucose is managed can have a substantial impact on cardiovascular outcomes. In this document, we discuss the role of glycemic management (both in intensity of control and choice of medications) in cardiovascular outcomes. It is becoming clear that the cardiologist needs both to consider T2DM in cardiovascular treatment decisions and potentially to help guide the selection of glucose-lowering medications. Our statement provides a comprehensive summary of effective, patient-centered management of CAD in patients with T2DM, with emphasis on the emerging evidence. Given the increasing prevalence of T2DM and the accumulating evidence of the need to consider T2DM in treatment decisions, this knowledge will become ever more important to optimize our patients’ cardiovascular outcomes.
Abstract 12269: The Association of Cardiovascular Disease and Future Cancer
Authors: Emily Lau, Samantha M Paniagua, Elizabeth Liu, Manol Jovani, Shawn Li, Katherine Takvorian, Vasan S Ramachandran, Greta L Splanksy, Bernard Kreger, Martin Larson, Daniel Levy, Jennifer E Ho
Journal: Circulation (2019)

Introduction: Emerging data support a potential link between CVD and cancer, but whether this is due to shared risk factors or other mechanisms is unknown. We sought to investigate the association ...
Altered metabolism in pulmonary hypertension: fuelling the fire or just smoke?
Authors: Daisy Duan, Chenjuan Gu, Jonathan C. Jun
Journal: European Respiratory Journal (2020)

Pulmonary arterial hypertension (PAH) is characterised by progressive obliteration of the pulmonary vasculature, culminating in right-sided heart failure (HF). In recent years, studies have observed an association between systemic metabolic dysfunction, PAH and right ventricular failure [1]. Patients with PAH have an increased prevalence of obesity [2] and type 2 diabetes [3, 4]. Interestingly, abnormal glucose metabolism is evident even in non-diabetic individuals with PAH [5–7], and serves as an independent predictor of prognosis [8]. Glucose and fat metabolism are altered in pulmonary arterial hypertension, but it is not yet clear if these changes are causes or effects of the disease <http://bit.ly/3cWyf66>
Tumor-neuroglia interaction promotes pancreatic cancer metastasis
Authors: Dan Su, Xiaofeng Guo, Leyi Huang, Huilin Ye, Zhiguo Li, Longfa Lin, Rufu Chen, Quanbo Zhou
Journal: Theranostics (2020)

Rationale: The peripheral nervous system (PNS) plays an important role in tumor growth and progression. Schwann cells (SCs), the main glia cells of the PNS, augment cancer metastasis in contact-dependent or contact-independent manner in various malignancies. In the present study, we aimed to determine whether interplay between pancreatic cancer cells and SCs via paracrine signaling contributes to cancer progression. Methods: Immunofluorescence analysis was performed to reveal the distribution of SCs in PDAC tissues and to determine the prognostic value and clinicopathological relevance of the level of intra‑tumoral SC markers for patients diagnosed with PDAC. Transwell assays and wound healing assays were carried out to investigate the influence of SC conditioned medium (SCM), SC co‑culture, or co-cultured CM on the migratory and invasive abilities of pancreatic cancer cells. The mechanism of SCs induced cancer cells migration and invasion was confirmed using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assays (ELISAs), western blotting, immunofluorescence, immunohistochemistry, siRNA-mediated gene interference, and an in vivo mouse model. Results: Immunofluorescence analysis of tissue samples revealed that there were two different types of SCs distributed in the tumor microenvironment, the presence of which correlated with several clinicopathological characteristics and overall survival for patients with PDAC. Although SCM had no impact on the motility and invasiveness of tumor cells, both co-cultivation with SCs and co‑cultured CM enhanced pancreatic cancer cell migration and invasion. Mechanistically, SC‑derived Interleukin 6 (IL6), which was induced by co-culture with pancreatic cancer cells, augmented cancer cell migration and invasion by activating STAT3 signaling in cancer cells, while IL6 neutralization or STAT3 downregulation abrogated these effects. Furthermore, Interleukin 1β (IL1β), secreted by tumor cells, activated the nuclear actor (NF)-kappa B pathway in SCs, resulting in increased cytokines production, including IL6, while inhibiting the IL1β-IL1R1 axis led to inactivation of NF-kappa B signaling and downregulated cytokines expression in SCs. Interfering with tumor-neuroglia crosstalk impeded cancer cell dissemination in vivo. Conclusion: Schwann cells were extensively distributed in the PDAC tumor microenvironment and high level of intra-tumoral SC markers could serve as an independent prognostic factor for poor survival of patients with PDAC. The tumor-neuroglia interaction is indispensable for SCs to acquire a tumor-facilitating phenotype. Targeting the tumor-neuroglia interplay might be a promising strategy to treat PDAC.
Insulin-Like Growth Factors Are Key Regulators of T Helper 17 Regulatory T Cell Balance in Autoimmunity
Authors: Daniel DiToro, Stacey N. Harbour, Jennifer K. Bando, Gloria Benavides, Steven Witte, Vincent A. Laufer, Carson Moseley, Jeffery R. Singer, Blake Frey, Henrietta Turner, Jens Bruning, Victor Darley-Usmar, Min Gao, Cheryl Conover, Robin D. Hatton, Stuart Frank, Marco Colonna, Casey T. Weaver
Journal: Immunity (2020)
COVID-19 with Different Severities: A Multicenter Study of Clinical Features
Authors: Yun Feng, Yun Ling, Tao Bai, Yusang Xie, Jie Huang, Jian Li, Weining Xiong, Dexiang Yang, Rong Chen, Fangying Lu, Yunfei Lu, Xuhui Liu, Yuqing Chen, Xin Li, Yong Li, Hanssa Dwarka Summah, Huihuang Lin, Jiayang Yan, Min Zhou, Hongzhou Lu, Jieming Qu
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: The coronavirus disease (COVID-19) pandemic is now a global health concern.Objectives: We compared the clinical characteristics, laboratory examinations, computed tomography images, and treatments of patients with COVID-19 from three different cities in China.Methods: A total of 476 patients were recruited from January 1, 2020, to February 15, 2020, at three hospitals in Wuhan, Shanghai, and Anhui. The patients were divided into four groups according to age and into three groups (moderate, severe, and critical) according to the fifth edition of the Guidelines on the Diagnosis and Treatment of COVID-19 issued by the National Health Commission of China.Measurements and Main Results: The incidence of comorbidities was higher in the severe (46.3%) and critical (67.1%) groups than in the moderate group (37.8%). More patients were taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the moderate group than in the severe and critical groups. More patients had multiple lung lobe involvement and pleural effusion in the critical group than in the moderate group. More patients received antiviral agents within the first 4 days in the moderate group than in the severe group, and more patients received antibiotics and corticosteroids in the critical and severe groups. Patients >75 years old had a significantly lower survival rate than younger patients.Conclusions: Multiple organ dysfunction and impaired immune function were the typical characteristics of patients with severe or critical illness. There was a significant difference in the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers among patients with different severities of disease. Involvement of multiple lung lobes and pleural effusion were associated with the severity of COVID-19. Advanced age (≥75 yr) was a risk factor for mortality.
Association of Antibiotic Exposure With Survival and Toxicity in Patients With Melanoma Receiving Immunotherapy
Authors: Jahan J Mohiuddin, Brian Chu, Andrea Facciabene, Kendra Poirier, Xingmei Wang, Abigail Doucette, Cathy Zheng, Wei Xu, Emily J Anstadt, Ravi K Amaravadi, Giorgos C Karakousis, Tara C Mitchell, Alexander C Huang, Jacob E Shabason, Alexander Lin, Samuel Swisher-McClure, Amit Maity, Lynn M Schuchter, John N Lukens
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background Gut microbial diversity is associated with improved response to immune checkpoint inhibitors (ICI). Based on the known detrimental impact that antibiotics have on microbiome diversity, we hypothesized that antibiotic receipt prior to ICI would be associated with decreased survival. Methods Patients with stage III and IV melanoma treated with ICI between 2008 and 2019 were selected from an institutional database. A window of antibiotic receipt within 3 months prior to the first infusion of ICI was prespecified. The primary outcome was overall survival (OS), and secondary outcomes were melanoma-specific mortality and immune-mediated colitis requiring intravenous steroids. All statistical tests were two-sided. Results There were 568 patients in our database of which 114 received antibiotics prior to ICI. Of the patients, 35.9% had stage III disease. On multivariable Cox proportional hazards analysis of patients with stage IV disease, the antibiotic-exposed group had statistically significantly worse OS (hazard ratio [HR] = 1.81, 95% confidence interval [CI] = 1.27 to 2.57; P &amp;lt;.001). The same effect was observed among antibiotic-exposed patients with stage III disease (HR = 2.78, 95% CI = 1.31 to 5.87; P =.007). When limited to only patients who received adjuvant ICI (n = 89), antibiotic-exposed patients also had statistically significantly worse OS (HR = 4.84, 95% CI = 1.09 to 21.50; P =.04). The antibiotic group had a greater incidence of colitis (HR = 2.14, 95% CI = 1.02 to 4.52; P =.046). Conclusion Patients with stage III and IV melanoma exposed to antibiotics prior to ICI had statistically significantly worse OS than unexposed patients. Antibiotic exposure was associated with greater incidence of moderate to severe immune-mediated colitis. Given the large number of antibiotics prescribed annually, physicians should be judicious with their use in cancer populations likely to receive ICI.
Role of Impaired Nutrient and Oxygen Deprivation Signaling and Deficient Autophagic Flux in Diabetic CKD Development: Implications for Understanding the Effects of Sodium-Glucose Cotransporter 2-Inhibitors
Authors: Milton Packer
Journal: Journal of the American Society of Nephrology (2020)

Growing evidence indicates that oxidative and endoplasmic reticular stress, which trigger changes in ion channels and inflammatory pathways that may undermine cellular homeostasis and survival, are critical determinants of injury in the diabetic kidney. Cells are normally able to mitigate these cellular stresses by maintaining high levels of autophagy, an intracellular lysosome-dependent degradative pathway that clears the cytoplasm of dysfunctional organelles. However, the capacity for autophagy in both podocytes and renal tubular cells is markedly impaired in type 2 diabetes, and this deficiency contributes importantly to the intensity of renal injury. The primary drivers of autophagy in states of nutrient and oxygen deprivation-sirtuin-1 (SIRT1), AMP-activated protein kinase (AMPK), and hypoxia-inducible factors (HIF-1α and HIF-2α)-can exert renoprotective effects by promoting autophagic flux and by exerting direct effects on sodium transport and inflammasome activation. Type 2 diabetes is characterized by marked suppression of SIRT1 and AMPK, leading to a diminution in autophagic flux in glomerular podocytes and renal tubules and markedly increasing their susceptibility to renal injury. Importantly, because insulin acts to depress autophagic flux, these derangements in nutrient deprivation signaling are not ameliorated by antihyperglycemic drugs that enhance insulin secretion or signaling. Metformin is an established AMPK agonist that can promote autophagy, but its effects on the course of CKD have been demonstrated only in the experimental setting. In contrast, the effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors may be related primarily to enhanced SIRT1 and HIF-2α signaling; this can explain the effects of SGLT2 inhibitors to promote ketonemia and erythrocytosis and potentially underlies their actions to increase autophagy and mute inflammation in the diabetic kidney. These distinctions may contribute importantly to the consistent benefit of SGLT2 inhibitors to slow the deterioration in glomerular function and reduce the risk of ESKD in large-scale randomized clinical trials of patients with type 2 diabetes.
Cytomegalovirus Encephalopathy during Brain Tumor Irradiation
Authors: Sean E. Lawler, E. Antonio Chiocca, Charles H. Cook
Journal: Clinical Cancer Research (2020)

Some patients with brain cancer show extremely short survival postradiochemotherapy treatment for unknown reasons. Recent work shows that this is closely linked to encephalopathy associated with reactivation of latent cytomegalovirus in the host. Importantly, survival can be enhanced by treatment with antiviral drugs.See related article by Goerig et al., p. 3259.
Second-Line Bosutinib in Patients with Chronic Phase Chronic Myeloid Leukemia (CP CML) Resistant or Intolerant to Prior Imatinib: An 8-Year Update
Authors: Tim H. Brümmendorf, Carlo Gambacorti-Passerini, Dong-Wook Kim, Yeow Tee Goh, Iryna Dyagil, Katia B Pagnano, Árpád Bátai, Anna G Turkina, Jean M. Aguiar, Eric Leip, Jorge E. Cortes
Journal: Blood (2017)
Death from Covid-19 of 23 Health Care Workers in China
Authors: Mingkun Zhan, Yaxun Qin, Xiang Xue, Shuaijun Zhu
Journal: New England Journal of Medicine (2020)

Death from Covid-19 of Health Workers in China This report describes the deaths from Covid-19 of 23 health care workers, including physicians, surgeons, a nurse, and an electrocardiography technici...
Serum Amyloid A is a biomarker of severe Coronavirus Disease and poor prognosis
Authors: Huan Li, Xiaochen Xiang, Hongwei Ren, Lingli Xu, Lisha Zhao, Xiaoqiong Chen, Hui Long, Qiang Wang, Qingming Wu
Journal: Journal of Infection (2020)

To explore the significance of SAA in evaluating the severity and prognosis of COVID-19.
Soft‐tissue sarcoma in adults: An update on the current state of histiotype‐specific management in an era of personalized medicine
Authors: Adriana C. Gamboa, Alessandro Gronchi, Kenneth Cardona
Journal: CA A Cancer Journal for Clinicians (2020)

Soft-tissue sarcomas (STS) are rare tumors that account for 1% of all adult malignancies, with over 100 different histologic subtypes occurring predominately in the trunk, extremity, and retroperitoneum. This low incidence is further complicated by their variable presentation, behavior, and long-term outcomes, which emphasize the importance of centralized care in specialized centers with a multidisciplinary team approach. In the last decade, there has been an effort to improve the quality of care for patients with STS based on anatomic site and histology, and multiple ongoing clinical trials are focusing on tailoring therapy to histologic subtype. This report summarizes the latest evidence guiding the histiotype-specific management of extremity/truncal and retroperitoneal STS with regard to surgery, radiation, and chemotherapy.
The COVID-19 pandemic will have a long-lasting impact on the quality of cirrhosis care
Authors: Elliot B. Tapper, Sumeet K. Asrani
Journal: Journal of Hepatology (2020)

The coronavirus disease 2019 (COVID-19) pandemic has shattered the meticulously developed processes by which we delivered quality care for patients with cirrhosis. Care has been transformed by the crisis, but enduring lessons have been learned. In this article, we review how COVID-19 will impact cirrhosis care. We describe how this impact unfolds over 3 waves; i) an intense period with prioritized high-acuity care with delayed elective procedures and routine care during physical distancing, ii) a challenging 'return to normal' following the end of physical distancing, with increased emergent decompensations, morbidity, and systems of care overwhelmed by the backlog of deferred care, and iii) a protracted period of suboptimal outcomes characterized by missed diagnoses, progressive disease and loss to follow-up. We outline the concrete steps required to preserve the quality of care provided to patients with cirrhosis. This includes an intensification of the preventative care provided to patients with compensated cirrhosis, proactive chronic disease management, robust telehealth programs, and a reorganization of care delivery to provide a full service of care with flexible clinical staffing. Managing the pandemic of a serious chronic disease in the midst of a global infectious pandemic is challenging. It is incumbent upon the entire healthcare establishment to be strong enough to weather the storm. Change is needed.
A validated composite organ and hematologic response model for early assessment of treatment outcomes in light chain amyloidosis
Authors: Surbhi Sidana, Paolo Milani, Moritz Binder, Marco Basset, Nidhi Tandon, Andrea Foli, Angela Dispenzieri, Morie A. Gertz, Suzanne R. Hayman, Francis K. Buadi, Martha Q. Lacy, Prashant Kapoor, Nelson Leung, S. Vincent Rajkumar, Giampaolo Merlini, Giovanni Palladini, Shaji K. Kumar
Journal: Blood Cancer Journal (2020)

Abstract Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n = 473; validation cohort, Pavia: n = 575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using incremental scoring based on hazard ratios with scores of 0–3 for HR (0—CR, 1—VGPR, 2—PR, 3—no response) and 0–2 for OR (0—AOR, 1—MOR, 2—NOR). Patients could be divided into two distinct CHOR groups (scores 0–3 and 4–5), with median OS in group 1 and group 2: Not reached vs. 34 months, p &lt; 0.001 [Mayo] and 87 vs. 23 months, p &lt; 0.001 [Pavia]. In conclusion, we developed a model that can assess multiple organs concurrently, and integrate both HR and OR assessments to determine early clinical benefit with treatment, which may be used as a surrogate end-point in trials and to compare outcomes with different therapies.
COVID-19 and the gastrointestinal tract: more than meets the eye
Authors: Siew C Ng, Herbert Tilg
Journal: Gut (2020)

<h3>Objectives</h3> The meaning that patients and carers attribute to their experience of palliative care is fundamental to the provision, practice and evaluation of optimal care. This analysis aims to establish contemporary key practices and priorities from the perspective of patients and carers. <h3>Methods</h3> Thematic analysis was applied to 594 anonymised free text responses from patients and carers documenting their experiences of palliative care. <h3>Results</h3> The emotional experience of care is the most significant aspect documented by patients and carers. It refers to the process of care in key domains of respect, renewal, refuge and restorative care. Patients and carers described care as either enabling or directly provided. The emotional experience of care was not confined to psychosocial need and constituted a core practice drawing on professional expertise and interpersonal skills, some of which may be taken for granted by staff themselves. <h3>Conclusions</h3> The emotional experience of care is examined as a practice rather than a topic, acknowledging that patients and carers documented the performance of care and the resulting impact in a variety of situations. The emotional experience of care comprises key aspects of contextual care facilitating autonomy and connectedness. It is embedded in relationships mediated by communication and tenor of care. The perspective of patients and carers places the emotional experience of palliative care centrally. This has implications for future service evaluation and the incorporation of this skill-based outcome alongside more traditional outcome measures such as the amelioration of physical symptoms.