tbuckley/cabot-search huggingface dataset:
Cancer treatments fall as referrals are slow to recover, show figures
Authors: Elisabeth Mahase
Journal: BMJ (2020)

The number of cancer patients starting treatment between April and July 2020 in the UK has reduced by 26% (31 000) compared with the same period in 2019, according to figures analysed by Cancer Research UK.1

The charity said the drop is from a reduction in the number of people being referred to or attending secondary care, as well as the pause of screening programmes and some diagnostic tests because of the pandemic.

Figures for England show that urgent suspected lung cancer referrals have been the slowest to recover since April, with numbers still only 60% of pre-covid-19 levels at the end of September. There were 17 500 two week referrals made for …
FRI0057 Effects of cyclosporine/methotrexate combination therapy followed by single agent treatment on radiographic progression in early rheumatoid arthritis
Authors: A Marchesoni, N Battafarano, M Arreghini, M Cagnoli, P Prudente, R Pellerito, S Tosi
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Early treatment of severe rheumatoid arthritis (RA) with cyclosporine (CsA) and methotrexate (MTX) in combination is now considered one of the best strategies to control the arthritic symptoms and prevent structural joint deterioration. <h3>Objectives</h3> This trial was aimed at evaluating the clinical and radiographic outcome of a cohort of patients with early rheumatoid arthritis (RA) first treated with an association of CsA and MTX, and then randomly stepped down to one of two agents. <h3>Methods</h3> Fifty-seven patients (54 F and 3 M) (mean age 49.5 yr., range 20–64) with early, active RA (mean disease duration 0.8 yr., range 0.5–2), were treated with CsA (3 mg/kg/day) and MTX (10–15 mg/week) in combination for 6 months and then 49 of them were randomised to receive single therapy with either CsA (22 patients) or MTX (27 patients) for another 18 months. The radiographic evaluation was carried out on an intention-to-treat basis on all of the patients who completed the combination period using hand and foot radiographs taken at baseline, and after 12 and 24 months. The reading was blindly performed by two radiologists using the 32-joint damage score (DS) of the Larsen-Dale method and the count of the eroded joints (EJC). <h3>Results</h3> Seven patients discontinued the study therapy because of adverse events during the first period of the trial, and 18 patients prematurely withdrew, mainly because of lack of efficacy, during the second study phase. Using the last-observation-carried-forward method, the good or moderate responders according the EULAR criteria were 42 (73.7%) at the end of the 6-month combination period, and 36 (73.5%) at the end of the single agent phase. Overall, safety and tolerability was good. At baseline, the mean DS (± SEM) in the CsA and MTX groups was respectively 5.1 ± 1.5 and 5.0 ± 1.7, and the mean EJC (± SEM) was 1.1 ± 0.3 and 0.7 ± 0.3. The differences in the radiographic scores after 12 and 24 months were as follows. In the CsA group: DS12 month-0 = +7.3 ± 3.2, EJC12 month-0 = +2.1 ± 1.1, DS24 month-0 = +10.5 ± 2.6 (p &lt; 0.01), EJC24 month-0 = +3.2 ± 0.8 (p &lt; 0.01). In the MTX group: DS12 month-0 = +5.2 ± 2.0, EJC12 month-0 = +1.5 ± 0.7 (p = 0.01), DS24 month-0 = +10.4 ± 1.7 (p &lt; 0.01), EJC24 month-0 = +2.3 ± 0.5 (p &lt; 0.01). The comparison between the two therapy groups did not show any significant difference. <h3>Conclusion</h3> Radiographic deterioration occurred in both treatment groups but was mild and slow. Combination therapy with CsA and MTX followed by single agent maintenance treatment seems to induce a persistent retardation of radiographic damage. Longer period of combination therapy could yield better control of the joint structural damage.
Patients With Severely Reduced Ejection Fraction Undergoing Revascularization—Is Something Missing?
Authors: Amy E. Cheney, Ravi S. Hira
Journal: JAMA Cardiology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
An Early-Onset Subgroup of Type 2 Diabetes: A Multigenerational, Prospective Analysis in the Framingham Heart Study
Authors: Justin B. Echouffo-Tcheugui, Teemu J. Niiranen, Elizabeth L. McCabe, Mir Henglin, Mohit Jain, Ramachandran S. Vasan, Martin G. Larson, Susan Cheng
Journal: Diabetes Care (2020)

OBJECTIVE To assess the relation of type 2 diabetes occurring earlier (age &amp;lt;55 years) versus later in life to the risk of cardiovascular death and to diabetes in offspring. RESEARCH DESIGN AND METHODS In the Framingham Heart Study, a community-based prospective cohort study, glycemic status was ascertained at serial examinations over six decades among 5,571 first- and second-generation participants with mortality data and 2,123 second-generation participants who initially did not have diabetes with data on parental diabetes status. We assessed cause of death in a case (cardiovascular death)–control (noncardiovascular death) design and incident diabetes in offspring in relation to parental early-onset diabetes. RESULTS Among the participants in two generations (N = 5,571), there were 1,822 cardiovascular deaths (including 961 coronary deaths). The odds of cardiovascular versus noncardiovascular death increased with decreasing age of diabetes onset (P &amp;lt; 0.001 trend). Compared with never developing diabetes, early-onset diabetes conferred a 1.81-fold odds (95% CI 1.10–2.97, P = 0.02) of cardiovascular death and 1.75-fold odds (0.96–3.21, P = 0.07) of coronary death, whereas later-onset diabetes was not associated with greater risk for either (P = 0.09 for cardiovascular death; P = 0.51 for coronary death). In second-generation participants, having a parent with early-onset diabetes increased diabetes risk by 3.24-fold (1.73–6.07), whereas having one or both parents with late-onset diabetes increased diabetes risk by 2.19-fold (1.50–3.19). CONCLUSIONS Our findings provide evidence for a diabetes subgroup with an early onset, a stronger association with cardiovascular death, and higher transgenerational transmission.
Folic acid-modified Exosome-PH20 enhances the efficiency of therapy via modulation of the tumor microenvironment and directly inhibits tumor cell metastasis
Authors: Chunxiang Feng, Zhiyong Xiong, Cheng Wang, Wen Xiao, Haibing Xiao, Kairu Xie, Ke Chen, Huageng Liang, Xiaoping Zhang, Hongmei Yang
Journal: Bioactive Materials (2020)

High accumulation of hyaluronan (HA) in the tumor microenvironment leads to an increase in the interstitial pressure and reduction perfusion of drugs. Furthermore, high molecular-weight (HMW)-HA suppresses M1 macrophage polarization, enhances M2 polarization, and induces immunosuppression. Hyaluronidase treatment have attempted to decrease the quantity of HA in tumors. However, hyaluronidase-driven HA degradation driven accelerates tumor cell metastasis, which is a major cause of mortality in cancer patients. Thus, we designed a novel exosome-based drug delivery system (DDS), named Exos-PH20-FA, using genetic engineering to express human hyaluronidase (PH20) and self-assembly techniques to modify the exosomes with folic acid (FA). Our results show that Exos-PH20-FA degraded HMW-HA to low-molecular-weight (LMW)-HA. Moreover, LMW-HA polarized macrophages to the M1 phenotype and reduced the number of relevant immunosuppressive immunocytes which changed the immune microenvironment from an immunosuppressive to immunosupportive phenotype. Furthermore, we demonstrated Exos-PH20-FA directly reduced hyaluronidase-induced metastasis of tumor cells. This tumor treatment also allowed an enhanced delivery of chemotherapy by tumor-targeting effect with FA modification. Our findings indicate that Exos-PH20-FA improves tumor treatment efficiency and reduces the side effects of hyaluronidase treatment, namely tumor cell metastasis. This all-in-one exosome-based HA targeting DDS maybe a promising treatment that yields more efficient and safer results.
Application of transthoracic shear-wave ultrasound elastography in lung lesions
Authors: Yao-Wen Kuo, Yen-Lin Chen, Huey-Dong Wu, Ying-Chun Chien, Chun-Kai Huang, Hao-Chien Wang
Journal: European Respiratory Journal (2020)

Introduction Tissue stiffness information may help in the diagnosis of lung lesions. This study aimed to investigate and validate the application of transthoracic two-dimensional shear-wave ultrasound elastography in differentiating malignant from benign subpleural lung lesions. Methods This study involved one retrospective observational derivation cohort from January 2016 to December 2017 and one prospective observational validation cohort from December 2017 to December 2019. The inclusion criterion was radiographic evidence of pulmonary lesions. The patients were categorised into air bronchogram and hypoechoic groups based on B-mode grayscale images. The elasticity of subpleural lung lesions with acceptable shear-wave propagation was measured. Diagnoses were made on the basis of pathology, microbiological studies or following up the clinical course for at least 6 months. Results A total of 354 patients were included. Among the 121 patients in the derivation cohort, a receiver operating characteristic curve was constructed and the cut-off point to differentiate benign from malignant lesions was 65 kPa with a Youden index of 0.60 and an accuracy of 84.3%. Among the 233 patients in the validation cohort, the diagnostic performance was maintained, with a Youden index of 0.65 and an accuracy of 86.7%. Upon applying the cut-off point to the air bronchogram group, the Youden index was 0.70 and the accuracy was 85.0%. Conclusions This study validated the application of transthoracic shear-wave ultrasound elastography for assessing lung malignancy. A cut-off point of 65 kPa is suggested for predicting lung malignancy. Furthermore, for pulmonary air bronchogram lesions with high elasticity, tissue proofing should be considered because of the high possibility of malignancy.
An evaluation of adult cancer-related neuropathic pain treatment at a large academic medical center.
Authors: Elizabeth Kyung Ko, Ashley Elizabeth Glode, Garth C. Wright
Journal: Journal of Clinical Oncology (2020)

168 Background: Cancer-related neuropathic pain (CNP) is a common comorbidity among patients due to treatment and/or tumors that can cause neuronal damage. At present, there is no proven method to prevent CNP and no published widely followed national guideline for CNP management with a defined treatment algorithm. Further evaluation of CNP treatment is needed to help guide the development of clinical algorithms for CNP management. Methods: Health Data Compass, a data mining warehouse, was used to identify adults treated at the University of Colorado Hospital (UCH) who had a new diagnosis of cancer between January 1, 2014 and May 31, 2019 in addition to neuropathy during the same time frame. Individual patient electronic medical records were then reviewed for information unable to be obtained through Health Data Compass. The primary objective of the study was to describe CNP treatment at our facility. Descriptive statistics were used to define study population demographics and the primary outcome. Results: A total of 316 patients met study inclusion. The majority of the patients were white (86.7%) and female (67.4%). The most commonly included cancer types were breast (39.4%) and gastrointestinal (35.6%). Patients with all cancer stages were represented in the study. The majority of patients (n = 283) had a diagnosis code of neuropathy on or after the date of their cancer diagnosis; 33 patients had neuropathy documented prior to their cancer diagnosis. The most common CNP management strategies included: opioids only (37.7%), opioids, gabapentin or pregabalin, and an antidepressant (20.3%), opioids and antidepressants (19.6%), or opioids and gabapentin or pregabalin (17.7%). Nearly half of medications used in CNP were not prescribed prior to the patient’s neuropathy diagnosis date (47.3%). Approximately one-third of the patients (33%) had no dose changes from their initial CNP treatment dose. Conclusions: We completed a large single center study to identify the most commonly used medications for CNP treatment. The study included a wide variety of cancer types and all stages. Opioids were the most commonly used medication to treat CNP at UCH. Next steps will be to evaluate the efficacy of opioids compared to other treatment combinations for the management of CNP.
Fibroblast Growth Factor Receptor Inhibitors and Nonuremic Calciphylaxis
Authors: Jesse Hirner, James M. Cleary, Anthony Sheets, George Murphy, Nicole LeBoeuf
Journal: JAMA Dermatology (2020)

This case report describes a woman in her 70s with type 2 diabetes, hypertension, idiopathic thrombocytopenia, and metastatic cholangiocarcinoma with an fibroblast growth factor receptor 2 translocation.
A Space–Time Continuum for Immunotherapy Biomarkers in Gastroesophageal Cancer?
Authors: Samuel J. Klempner, Vivek Upadhyay, Joseph Chao
Journal: Clinical Cancer Research (2020)

In an annotated series of gastroesophageal adenocarcinomas differences in PD-L1 expression and tumor mutation burden occur between both paired contemporaneous primary and metastatic biopsies and pre/posttreatment samples. This work has implications for optimizing patient selection, serial testing, need for mechanistic understanding, and may underlie variable responses to checkpoint inhibitors in gastroesophageal cancers.See related article by Zhou et al., p. 6453.
CAR-T cells targeting a nucleophosmin neoepitope exhibit potent specific activity in mouse models of acute myeloid leukaemia
Authors: Guozhu Xie, Nikola A. Ivica, Bin Jia, Yingzhong Li, Han Dong, Yong Liang, Douglas Brown, Rizwan Romee, Jianzhu Chen
Journal: Nature Biomedical Engineering (2020)
Standardization of cardiac monitoring practices in patients receiving cardiotoxic cancer therapy at an ambulatory oncology center.
Authors: Hannah DeLuna, Thomas A. Hensing, Bruce Brockstein, Amit Pursnani, Poornima Saha, George W. Carro, Jamie Feld, Rachel Mees, Katie Birks, Kara Catsaros, Dmitriy Velikov
Journal: Journal of Clinical Oncology (2020)

251 Background: A significant number of cancer-directed therapies are associated with cardiotoxicity. This adverse effect is well-established in anthracyclines and anti-HER2 agents. At our ambulatory oncology practice, the recent availability of echocardiograms with strain imaging has prompted an evaluation of current practices for cardiotoxicity monitoring. A review of the electronic health record (EHR) in 2019 found that although our institution maintains high rates of baseline monitoring, follow-up monitoring is not standardized and not consistent between different practices. Methods: A multidisciplinary team was formed to conduct a quality improvement project with the aim of increasing the rate of follow-up monitoring in patients who receive anthracyclines or infusional anti-HER2 agents. A survey of providers identified the potential reasons that follow-up cardiac monitoring was not completed. A Pareto chart showed that lack of familiarity with clinical necessity and appropriate timing were the most common barriers to follow-up monitoring. Our first plan-do-study-act focused on addressing these barriers, and a pilot in breast cancer treatment plans was started. Cardiac monitoring orders were added to curative intent protocols containing doxorubicin, trastuzumab, or pertuzumab. Education was provided to physician and nursing teams regarding utility and timing of cardiotoxicity monitoring. Collaboration with the cardiology group ensured timely access and result turnaround time. Results: An initial review of the EHR was conducted to identify current trends in cardiac monitoring. The review showed that there was an increase in the use of echocardiograms with strain imaging for baseline and follow-up monitoring in our patients. From January to April 2020, there was a total of 102 echocardiogram orders which was a 23% increase compared to the same timeframe in the previous year. The majority (61%) of those echocardiogram orders included strain imaging compared to 8% in the previous year. Review of treatment plan utilization and appropriate timing of cardiac monitoring in breast cancer patients is ongoing. Conclusions: This quality improvement project suggests that efforts to standardize cardiac monitoring practices can be achieved through provider education and workflow modifications. Further long-term review of the EHR will be needed to determine whether the timing of follow-up monitoring is appropriate and to identify what changes to the intervention should be made.
SARS-CoV-2 induces inflammatory cytokine release, which may be exacerbated by immune checkpoint blockade
Authors: Layne Weatherford, Maria Lehn, McKenzie Crist, Chelsea Wendling, Kristin Hudock, Vinita Takiar, Trisha Wise-Draper
Journal: Clinical Cancer Research (2020)

Cancer patients infected with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have ahigher mortality rate compared to non-cancer patients  Recent anticancer treatment, including immunotherapy, isassociated with severe infection including development of acute respiratory distress syndrome (ARDS) and highlevels of cytokine release resulting in cytokine storm  Immune checkpoint inhibitors (ICIs) are approved for use inmultiple cancer types and function by blocking the interaction between PD-1 and its ligand PD-L1, activatingantitumor cytotoxic immune cells  However, ICIs can also increase inflammatory cytokine secretion, which maypredispose to the development of cytokine storm  In fact, we have shown via single-cell cytokine secretion analysisthat pembrolizumab (anti-PD-1 antibody) increases cytokine secretion by polyfunctional strength index, a measureof the percentage of cells secreting multiple functional cytokines  Therefore, we hypothesize that ICIs may worseninflammatory cytokine secretion and potentiate cytokine storm and downstream complications in COVID-19 patients Peripheral blood mononuclear cells (PBMCs) were isolated via Ficoll density gradient centrifugation from healthydonors, head and neck cancer (HNC) patients, and COVID-19-infected cancer patients  Flow cytometry wasperformed on patient PBMCs, after staining for viability and immune cell markers including CD3, CD8, CD19, andCD45  PBMCs were also activated overnight with low-dose IL-2, cocultured with Cal27 or HN5 cell lines, andsubjected to various treatment conditions  For non-COVID-19 patients, PBMCs were exposed to 25 nM SARS-CoV-2 recombinant spike (S) protein, a virulent protein associated with cytokine storm, or control prior to drug treatments Preliminary flow cytometry analysis showed that a COVID-19-positive patient with thyroid cancer had an increasedproportion of CD8+ cells compared with a COVID-negative ovarian cancer patient and healthy donor  RecombinantSARS-CoV-2 S protein caused increased secretion of IL-6, IL-2, perforin, and MIP-1b from PBMCs isolated fromboth healthy donors and HNC patients, which was measured by IsoLight Codeplex bulk cytokine analysis or ELISA We have previously shown that metformin, a commonly prescribed antidiabetes drug, decreases the proportion ofcells that secrete inflammatory cytokines such as IL-6, which is thought to be an important cytokine for cytokinestorm  Interestingly, we observed that metformin treatment resulted in decreased IL-6 secretion from PBMCsisolated from a COVID-19-positive patient  Results from this project suggest that ICIs may potentiate cytokine storm, and ongoing investigation will be informative to oncologists as to whether ICI treatment should be postponed insevere COVID-19 infections  In addition, metformin may be a novel potential treatment for COVID-19 patients toprevent and treat cytokine storm
Telehealth treatment engagement with Latinx populations during the COVID-19 pandemic
Authors: Michelle A Silva, Oscar F Rojas Perez, Luis M Añez, Manuel Paris
Journal: The Lancet Psychiatry (2020)

for which a relevant and consistent amount of evidence already exists, and others for which new interventions or further evidence is needed.Finally, policy makers would have a tool for selecting psychological interventions for specific conditions and disorders.The development of regulatory requirements would need action from international health organisations, such as WHO, Cochrane, the Campbell Collaboration, or other similar public health agencies.As a first step, these agencies could appoint an international panel of experts from different backgrounds, including representatives of scientific societies and other interested stakeholder organisations, with the aim of defining an initial set of requirements.The panel might adapt WHO's process for developing recommendations for clinical practice, to follow a transparent and structured methodological pathway.Applying these regulatory requirements could produce formularies of evidence-based psychological interventions.WHO might consider developing a list of essential psychological interventions, to complement the existing list of essential medicines, to increase access, availability, affordability, and appropriate use of psychological interventions supported by robust evidence of efficacy and tolerability.