tbuckley/cabot-search huggingface dataset:
A comparison of two models of multidisciplinary lung cancer care within a community-based healthcare system.
Authors: Meghan Meadows, Meredith Ray, Matthew Smeltzer, Nicholas Faris, Carrie Fehnel, Olawale Akinbobola, Bianca Jackson, Courtney Foust, Laura McHugh, Raymond S. Signore, Jeffrey Wright, Edward T. Robbins, Raymond U. Osarogiagbon
Journal: Journal of Clinical Oncology (2020)

36 Background: The Multidisciplinary Thoracic Oncology Conference (MTOC) model is easier to implement than the Multidisciplinary Clinic (MDC) model, but does not directly involve patients in decision-making. We compared the processes and outcomes of lung cancer care between patients discussed in a weekly MTOC versus those seen in a MDC. Methods: Prospective observational study of thoroughness of staging, stage confirmation (defined as biopsy of the stage-defining lesion), National Comprehensive Cancer Network guideline-concordant treatment, overall (OS) and event-free (EFS) survival of lung cancer patients in a community healthcare system’s MDC and MTOC from 2014-2019. We used the chi-square test and multivariable logistic regression to evaluate guideline-concordant treatment and stage confirmation; Kaplan-Meier curves and multivariable Cox regression were used to evaluate OS and EFS. We adjusted models for age, sex, race, insurance, smoking status, and histology. Results: 614 patients received care in MDC; 571 in MTOC. MDC patients were older (median age: 69 vs. 67); less likely to be active smokers (44% vs. 47%; p=0.03); more likely to have bimodal (98% v 95%, p=0.02) and trimodal staging (60% v 46%, p&lt;0.0001). The stage-confirmation rate (OR: 1.55; 95% CI: 1.22-1.96) and mediastinal stage confirmation rate (OR: 1.55; 95% CI: 1.23-1.95) were both significantly higher in MDC, even after adjustment (aOR: 1.60; 95% CI: 1.25-2.03); (aOR: 1.58, 95% CI: 1.25-2.00). A higher proportion of patients received guideline-concordant treatment in MDC than in MTOC (82% vs. 73%; OR: 1.63; 95% CI: 1.21-2.20) even after adjustment (aOR: 1.64; 95% CI: 1.20-2.24). However, MTOC patients had significantly better OS (p=0.03) and EFS (p=0.001) than MDC patients and a lower hazard of death (HR: 0.81; 95% CI: 0.67-0.98), even after adjusting for confounding variables (aHR: 0.79 95%CI: 0.66-0.95). Conclusions: Although the processes of lung cancer care delivery were better in MDC than in MTOC, survival was better in MTOC. Patient selection may have played a role in these survival differences. The MTOC model, as implemented, seems competitive with the MDC model and is worthy of further exploration as a more feasible model of multidisciplinary care. [Table: see text]
What kills patients with severe Covid-19 might also kill patients with terminal cancer
Authors: Lingbing Zhang
Journal: Clinical Cancer Research (2020)

Introduction: As a prominent clinical feature of severe Covid-19, cytokine storm has attracted enormous attentionrecently  It is generally believed that cytokine storm might be the underlying force leading to health exacerbation anddeath from severe Covid-19  However, the role of cytokine storm in terminal cancer has not been reported  In thisstudy, we investigated the role of cytokine storm in a murine tumor model that mimics the disease progression ofterminal cancer  We found that cytokine storm develops in terminal cancer and leads to cachexia, which is aprevalent and lethal syndrome of terminal cancer  Methods: 7-week old BALB/c mice were inoculated with 1 x10 C26 tumor cells subcutaneously  Mice body weightand health condition were monitored starting 7 days after tumor inoculation  At various time points, serum cytokines were measured, immune cells were analyzed with flow cytometry, and multiple organs were collected andprocessed for histopathologic assessment  Results: Growth of subcutaneously inoculated tumors without metastasis progressively induces host body weightloss and overall health deterioration  Cytokine storm characterized by elevated expression of multipleproinflammatory cytokines such as IL-1, IL-6, and TNF-a in blood develops accompanying the health deterioration In parallel with cytokine storm development, massive infiltration of Gr-1 positive cells occurs in vital organs (lung andliver) and brings severe tissue damage  Histopathologic check ruled out any tumor metastasis to these organs, which suggests that the inflammatory response is the cause of the multiple organ damage  Importantly, suppressionof the inflammatory response with interventions can completely reverse the cachexia syndrome and increasesurvival  Conclusions and Implication: Cytokine storm develops and plays an important role in the health exacerbation ofterminal cancer  Therefore, calming the cytokine storm with interventions that can suppress the inflammatoryresponse might represent a new and promising approach to the treatment of terminal cancer  This approach mayhave the potential to save many patients from imminent deaths, which are often not directly caused by organoccupation
Surgical Decompression for Space-Occupying Hemispheric Infarction
Authors: Hendrik Reinink, Eric Jüttler, Werner Hacke, Jeannette Hofmeijer, Eric Vicaut, Katayoun Vahedi, Janis Slezins, Yingying Su, Linlin Fan, Emre Kumral, Jacoba P. Greving, Ale Algra, L. Jaap Kappelle, H. Bart van der Worp, Hermann Neugebauer
Journal: JAMA Neurology (2020)

In patients with space-occupying hemispheric infarction, surgical decompression reduces the risk of death and increases the chance of a favorable outcome. Uncertainties, however, still remain about the benefit of this treatment for specific patient groups.To assess whether surgical decompression for space-occupying hemispheric infarction is associated with a reduced risk of death and an increased chance of favorable outcomes, as well as whether this association is modified by patient characteristics.MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Stroke Trials Registry were searched from database inception to October 9, 2019, for English-language articles that reported on the results of randomized clinical trials of surgical decompression vs conservative treatment in patients with space-occupying hemispheric infarction.Published and unpublished randomized clinical trials comparing surgical decompression with medical treatment alone were selected.Patient-level data were extracted from the trial databases according to a predefined protocol and statistical analysis plan. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline and the Cochrane Collaboration's tool for assessing risk of bias were used. One-stage, mixed-effect logistic regression modeling was used for all analyses.The primary outcome was a favorable outcome (modified Rankin Scale [mRS] score ≤3) at 1 year after stroke. Secondary outcomes included death, reasonable (mRS score ≤4) and excellent (mRS score ≤2) outcomes at 6 months and 1 year, and an ordinal shift analysis across all levels of the mRS. Variables for subgroup analyses were age, sex, presence of aphasia, stroke severity, time to randomization, and involved vascular territories.Data from 488 patients from 7 trials from 6 countries were available for analysis. The risk of bias was considered low to moderate for 6 studies. Surgical decompression was associated with a decreased chance of death (adjusted odds ratio, 0.16; 95% CI, 0.10-0.24) and increased chance of a favorable outcome (adjusted odds ratio, 2.95; 95% CI, 1.55-5.60), without evidence of heterogeneity of treatment effect across any of the prespecified subgroups. Too few patients were treated later than 48 hours after stroke onset to allow reliable conclusions in this subgroup, and the reported proportions of elderly patients reaching a favorable outcome differed considerably among studies.The results suggest that the benefit of surgical decompression for space-occupying hemispheric infarction is consistent across a wide range of patients. The benefit of surgery after day 2 and in elderly patients remains uncertain.
Preventing neuronal edema increases network excitability after traumatic brain injury
Authors: Punam A. Sawant-Pokam, Tyler J. Vail, Cameron S. Metcalf, Jamie L. Maguire, Thomas O. McKean, Nick O. McKean, K.C. Brennan
Journal: Journal of Clinical Investigation (2020)

Edema is an important target for clinical intervention after traumatic brain injury (TBI). We used in vivo cellular resolution imaging and electrophysiological recording to examine the ionic mechanisms underlying neuronal edema and their effects on neuronal and network excitability after controlled cortical impact (CCI) in mice. Unexpectedly, we found that neuronal edema 48 hours after CCI was associated with reduced cellular and network excitability, concurrent with an increase in the expression ratio of the cation-chloride cotransporters (CCCs) NKCC1 and KCC2. Treatment with the CCC blocker bumetanide prevented neuronal swelling via a reversal in the NKCC1/KCC2 expression ratio, identifying altered chloride flux as the mechanism of neuronal edema. Importantly, bumetanide treatment was associated with increased neuronal and network excitability after injury, including increased susceptibility to spreading depolarizations (SDs) and seizures, known agents of clinical worsening after TBI. Treatment with mannitol, a first-line edema treatment in clinical practice, was also associated with increased susceptibility to SDs and seizures after CCI, showing that neuronal volume reduction, regardless of mechanism, was associated with an excitability increase. Finally, we observed an increase in excitability when neuronal edema normalized by 1 week after CCI. We conclude that neuronal swelling may exert protective effects against damaging excitability in the aftermath of TBI and that treatment of edema has the potential to reverse these effects.
Treatment navigation to reduce emergency room (ER) visits in cancer patients.
Authors: Henrique Zanoni Fernandes, Carlos Frederico Pinto, Fernanda Navarro Loiola, Stela Maris Coelho, Michele Felix, Laura Gomes
Journal: Journal of Clinical Oncology (2020)

199 Background: The practice of conventional oncology has undoubtedly changed in the last 15 years, becoming more efficient, but also more complex and expensive. This complex care needs significant coordination. In the last 2 years in half of the continuing development of our care coordination working in the "Navigation Treatment" domain, the impact on reducing ER visits was, in media, 75%. Methods: In 2015 IOV developed a patient-centered Navigation System based on Kanban (board and visual signals-KNS) for managing the treatment plan of our patients that was successful. In 2016 with support of an educational grant from QTP-ASCO, we extended this system to manage pain to others cancers and treatment-related symptoms, education, resource referral or Coordination of multi-disciplinary care. This study addresses only decreased ER visits between Dec 15 and May 20 by all patients monitored by Nurses navigators. We measured the proportional reduction of ER visits related to pain to the total ER visits in three successive periods: development of the NKS (dec15-jul16), pilot phase (aug16-oct17), and as an adopted best practice (oct17-until today). The KNS comprises a set of standardized procedures and successive checks for patients in treatment based on three procedures: (a) standardized treatments prescriptions to pain and symptoms controls; (b) standardized follow up in 24 and 48 hours, 1, 2 and 4 weeks; and (c) manage side effects of opioids or other emerging problem (constipation, confusion, mucositis, diarrhea, fever, etc.). Any patient initiating opioid use is included in the KNS until opioid is discontinued. Once pain is adequately controlled, the frequency of checks become wider up to once a month if no toxicity is identified. Any new condition (will restart the 24-48 hours loop. The KNS is managed by oncology nurses using phone or video calls, messaging, and appointments; Mon-Sun from 6 AM to 8 PM. Results: The KNS managed a median of 204 (table*) patients per month during the last 32 months (Oct 17 to May 20). Patients with pain, symptoms, or side effects that were effectively managed by the team avoided an unwanted visit to the ER, in media by 75%. Pain represents 20% of ER visits generally; in pilot phase 15% of ER visits, and actually 4% of ER visits, an 80% reduction in pain-related ER visits. ER visits represent patients with uncontrolled pain and not effectively managed by the KNS. Conclusions: The development of a system to deliver more effective care patients resulted in a 75% reduction of ER visits and adequate pain control in our practice.
Identifying areas for quality improvement through outpatient mortality review.
Authors: Denise Gococo-Benore, Adam McLain Kase, Umair Majeed, Muhamad Alhaj Moustafa, Ruqin Chen, Sree Battu, Molly Kilpatrick, Maisha Robinson, Jennifer Cowart, Alvaro Moreno-Aspitia, Jeremy Clifton Jones, Sikander Ailawadhi, Taimur Sher, Pooja Prem Advani
Journal: Journal of Clinical Oncology (2020)

230 Background: Inpatient mortality review is commonly used to improve patient care. Individual review of outpatient deaths is less common, yet 30-day mortality after hospital stay is an important quality metric. In this study, we sought to identify opportunities for care improvement by reviewing outpatient mortalities for cancer patients who died within 30 days of hospitalization. Methods: We identified 48 patients at Mayo Clinic Florida, with a hematologic (heme) or solid tumor (onc) cancer, who died within 30 days of an index hospital stay in 2018. We created a 32-question review survey to address quality of care around the hospital stay. The review team consisted of 1) heme or onc attendings, 2) heme/onc fellows, and 3) palliative care attendings. Each case was reviewed by one member of each of the 3 groups, split into heme or onc cases. Discrepancies in objective data points were resolved by the research team. Results: Of 143 surveys sent to 13 physicians (3 heme), 112 responses from 11 physicians (1 heme) for 47 patients were received. Twenty-one patients (45%) received cancer therapy within 30 days of death, and 23 (49%) were admitted &gt;2 times in 2 months prior to death. For onc cases, attendings rated prognosis as discussed 83% of the time, vs 65% of fellows and 39% of palliative care; in heme cases, the attending rated prognosis as discussed 11% of the time, vs 86% of fellows and 50% of palliative care. In heme cases, the attending rated expected survival &lt;3 months in 33% of cases vs 71% by fellows and 89% by palliative care; in onc cases, the reviews were more consistent (79% attending, 85% fellow, 93% palliative care). See Table for timing of prognosis discussions and palliative care involvement. Conclusions: The most common improvement opportunities identified by reviewing heme/onc patients who died within 30 days of a hospital stay included documented prognosis discussion and involvement of palliative care. Opportunities differed between heme and onc patients. Future directions include identifying and mitigating barriers that providers face in reaching these goals for their patients. [Table: see text]
What the 2020 party conferences told us about the NHS’s future
Authors: Andy Cowper
Journal: BMJ (2020)

The main political parties’ annual conferences are usually important, newsworthy, and curious parts of each autumn’s political scene, and they serve a variety of functions. Conferences are an opportunity for party activists to meet, scheme, and gossip; for opposition parties to tell us what they’d do if given power; for well functioning governments to assert their authority and trumpet their successes; and for poorly functioning governments to relaunch themselves and “take back control” of the political news agenda.

Given the importance of public policy and public spending to the health service, and the NHS’s totemic role in British culture, it’s generally worth paying attention to these events. This year, as in so many areas of life, the covid-19 pandemic has forced radical changes to this annual ritual. Like almost all live events, the party conferences became online only affairs.

The most striking thing about the 2020 conferences was how little attention was given to the NHS and the broader health, social care, and local government system at any of the three main Westminster parties’ events. Given that we’re entering the second wave of covid-19, party …
Current state and future perspective of cardiovascular medicines derived from natural products
Authors: Chunhui Zhao, Sen Li, Junhong Zhang, Yuanyun Huang, Luoqi Zhang, Feng Zhao, Xia Du, Jinli Hou, Tong Zhang, Chenjing Shi, Ping Wang, Ruili Huo, Owen L. Woodman, Cheng Xue Qin, Haiyu Xu, Luqi Huang
Journal: Pharmacology & Therapeutics (2020)
Immune Checkpoint Inhibitor Therapy Aggravates T Cell–Driven Plaque Inflammation in Atherosclerosis
Authors: Kikkie Poels, Mandy M.T. van Leent, Celine Boutros, Hubert Tissot, Séverine Roy, Anu E. Meerwaldt, Yohana C.A. Toner, Myrthe E. Reiche, Pascal J.H. Kusters, Tsveta Malinova, Stephan Huveneers, Audrey E. Kaufman, Venkatesh Mani, Zahi A. Fayad, Menno P.J. de Winther, Aurelien Marabelle, Willem J.M. Mulder, Caroline Robert, Tom T.P. Seijkens, Esther Lutgens
Journal: JACC CardioOncology (2020)

Immunotherapy has revolutionized cancer treatment. However, immune checkpoint inhibitors (ICIs) that target PD-1 (programmed cell death protein-1) and/or CTLA-4 (cytotoxic T lymphocyte-associated antigen-4) are commonly associated with acute immune-related adverse events. Accumulating evidence also suggests that ICIs aggravate existing inflammatory diseases.As inflammation drives atherosclerotic cardiovascular disease, we studied the propensity of short-term ICI therapy to aggravate atherosclerosis.We used 18F-FDG (2-deoxy-2-[fluorine-18]fluoro-D-glucose) positron emission tomography-computed tomography to detect macrophage-driven vascular and systemic inflammation in pembrolizumab and nivolumab/ipilimumab-treated melanoma patients. In parallel, atherosclerotic Ldlr-/- mice were treated with CTLA-4 and PD-1 inhibition to study the proinflammatory consequences of immune checkpoint inhibition.ICI treatment did not affect 18F-FDG uptake in the large arteries, spleen, and bone marrow of melanoma patients, nor myeloid cell activation in blood and lymphoid organs in hyperlipidemic mice. In contrast, we found marked changes in the adaptive immune response (i.e., increased CD4+ effector T cell and CD8+ cytotoxic T cell numbers in lymphoid organs and the arterial wall of our hyperlipidemic mice). Although plaque size was unaffected, plaques had progressed toward a lymphoid-based inflammatory phenotype, characterized by a 2.7-fold increase of CD8+ T cells and a 3.9-fold increase in necrotic core size. Increased endothelial activation was observed with a 2.2-fold and 1.6-fold increase in vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, respectively.This study demonstrates that combination therapy with anti-CTLA-4 and anti-PD-1 antibodies does not affect myeloid-driven vascular and systemic inflammation in melanoma patients and hyperlipidemic mice. However, short-term ICI therapy in mice induces T cell-mediated plaque inflammation and drives plaque progression.
Mitochondrial mutations and mitoepigenetics: Focus on regulation of oxidative stress-induced responses in breast cancers
Authors: Kuo Chen, Pengwei Lu, Narasimha M. Beeraka, Olga A. Sukocheva, SubbaRao V. Madhunapantula, Junqi Liu, Mikhail Y. Sinelnikov, Vladimir N. Nikolenko, Kirill V. Bulygin, Liudmila M. Mikhaleva, Igor V. Reshetov, Yuanting Gu, Jin Zhang, Yu Cao, Siva G. Somasundaram, Cecil E. Kirkland, Ruitai Fan, Gjumrakch Aliev
Journal: Seminars in Cancer Biology (2020)
A National Commitment to Improve the Care of Patients With Hypertension in the US
Authors: Jerome M. Adams, Janet S. Wright
Journal: JAMA (2020)

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Hypoxia-induced myeloid derived growth factor promotes hepatocellular carcinoma progression through remodeling tumor microenvironment
Authors: Xu Wang, Jie Mao, Tao Zhou, Xingyi Chen, Haoyang Tu, Jinyan Ma, Yixuan Li, Yushi Ding, Yong Yang, Hongxi Wu, Xinying Tang
Journal: Theranostics (2020)

Purpose: Exploring and studying the novel target of hepatocellular carcinoma (HCC) has been extremely important for its treatment.The principal objective of this project is to investigate whether myeloid derived growth factor (MYDGF) could accelerate the progression of HCC, and how it works.Methods: Cell proliferation, clonal formation, sphere formation and xenograft tumor experiments were used to prove the critical role of MYDGF in HCC progression.Tumor angiogenesis, immune cell infiltration, macrophage chemotaxis and inflammatory cytokines detection were utilized to clarify how MYDGF remodeled the tumor microenvironment (TME) to accelerate the progress of HCC.Results: Here, we reported a secretory protein MYDGF, which could be induced by hypoxia, was significantly upregulated in HCC and associated with poor clinical outcomes.Using bioinformatics and experimental approaches, we found that MYDGF promotes cell proliferation in vitro and in vivo through a mechanism that might involve enhanced self-renewal of liver CSCs.Furthermore, MYDGF can also promote tumor angiogenesis, induce macrophages to chemotaxis into tumor tissue, and then release various inflammatory cytokines, including IL-6 and TNF-α, which ultimately aggravate inflammation of tumor microenvironment and accelerate HCC progression.Conclusions: We provided evidence that MYDGF could directly affect the self-renewal of liver CSCs, and indirectly aggravate the inflammatory microenvironment to accelerate the progression of HCC.
A whole blood test to measure SARS-CoV-2-specific response in COVID-19 patients
Authors: Linda Petrone, Elisa Petruccioli, Valentina Vanini, Gilda Cuzzi, Saeid Najafi Fard, Tonino Alonzi, Concetta Castilletti, Fabrizio Palmieri, Gina Gualano, Pietro Vittozzi, Emanuele Nicastri, Luciana Lepore, Andrea Antinori, Alessandra Vergori, Nadia Caccamo, Fabrizio Cantini, Enrico Girardi, Giuseppe Ippolito, Alba Grifoni, Delia Goletti
Journal: Clinical Microbiology and Infection (2020)