tbuckley/cabot-search huggingface dataset:
Management of Gliomas: Individualized Treatment Options
Authors: Louis Burt Nabors
Journal: Journal of the National Comprehensive Cancer Network (2020)

Optimizing treatment for patients with low-grade gliomas should focus on the role of radiation and chemotherapy, as well as the prognostic impact of molecular diagnostics (1p/19q and IDH status). For anaplastic oligodendroglioma, focus should be placed on molecular markers (particularly 1p/19q status) and combination treatment with chemotherapy (temozolomide or PCV [procarbazine, lomustine, and vincristine]) and radiation. For patients with malignant glioblastomas, the role of methylguanine methyl-transferase (MGMT) methylation status has become increasingly important to treatment decisions. MGMT methylation status should be considered in elderly patients and/or those with low performance status (methylated patients benefit from temozolomide) and a hypofractionated radiation schedule should be used.
AB0221 Familial mediterranean fever: analysis of 45 tunisian patients
Authors: SS Turki, CH Ben Taarit, R Goucha, E Abderrahim, F Ben Moussa, H Ben Maiz
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Familial mediterranean fever (FMF) is an inherited multisystem disease of unknown aetiology, characterised by recurrent, painful, self-limited episodes. <h3>Objectives</h3> The objectives of this study is to describe clinical profile, course and complications of 45 cases of FMF observed over a period of 25 years. <h3>Methods</h3> Retrospective review of 45 cases with FMF. <h3>Results</h3> Forty patients (88%) started their illness below the age of 10 years. Peritonitis occured in 84,4%, arthritis in 35,5%, pleuretis in 17,7% and erysipelas-like lesions in 31,1%. 21 patients developed renal amyloïdosis and 17 patients were subjected to unnecessary operative surgery. The arthritis was monoarticular in 85% and polyarticular in 15% and was seronegative in all patients (Rheumatoïd factor and antinuclear antibodies). The synovial attack showed a wide variation in the clinical presentation, course and duration of arthritis causing diagnostic difficulties. Renal amyloïdosis occurred in 21 patients after a mean duration of FMF 10,5 years (2 to 28 years). One patient had hematuria, kidney biopsy showed mesangial IgA glomerulonephritis. Among 32 patients treated with colchicine, 80% achieved a therapeutic response. <h3>Conclusion</h3> FMF is an inherited disease; colchicine remains the only efficient treatment to prevent both acute manifestations and amyloïdosis.
Nanoformulation of CCL21 greatly increases its effectiveness as an immunotherapy for neuroblastoma
Authors: Brittany J. Poelaert, Svetlana Romanova, Shelby M. Knoche, Madeline T. Olson, Bailee H. Sliker, Kaitlin Smits, Brittney L. Dickey, Alexandra E.J. Moffitt-Holida, Benjamin T. Goetz, Nuzhat Khan, Lynette Smith, Hamid Band, Aaron M. Mohs, Donald W. Coulter, Tatiana K. Bronich, Joyce C. Solheim
Journal: Journal of Controlled Release (2020)
Identification of Long Noncoding RNA H19 as a New Biomarker and Therapeutic Target in Right Ventricular Failure in Pulmonary Arterial Hypertension
Authors: Junichi Omura, Karima Habbout, Tsukasa Shimauchi, Wen-Hui Wu, Sandra Breuils-Bonnet, Eve Tremblay, Sandra Martineau, Valérie Nadeau, Kassandra Gagnon, Florence Mazoyer, Jean Perron, Francois Potus, Jian-Hui Lin, Hamza Zafar, David G. Kiely, Allan Lawrie, Stephen L. Archer, Roxane Paulin, Steeve Provencher, Olivier Boucherat, Sébastien Bonnet
Journal: Circulation (2020)

Right ventricular (RV) function is the major determinant for both functional capacity and survival in patients with pulmonary arterial hypertension (PAH). Despite the recognized clinical importance of preserving RV function, the subcellular mechanisms that govern the transition from a compensated to a decompensated state remain poorly understood and as a consequence there are no clinically established treatments for RV failure and a paucity of clinically useful biomarkers. Accumulating evidence indicates that long noncoding RNAs are powerful regulators of cardiac development and disease. Nonetheless, their implication in adverse RV remodeling in PAH is unknown.Expression of the long noncoding RNA H19 was assessed by quantitative PCR in plasma and RV from patients categorized as control RV, compensated RV or decompensated RV based on clinical history and cardiac index. The impact of H19 suppression using GapmeR was explored in 2 rat models mimicking RV failure, namely the monocrotaline and pulmonary artery banding. Echocardiographic, hemodynamic, histological, and biochemical analyses were conducted. In vitro gain- and loss-of-function experiments were performed in rat cardiomyocytes.We demonstrated that H19 is upregulated in decompensated RV from PAH patients and correlates with RV hypertrophy and fibrosis. Similar findings were observed in monocrotaline and pulmonary artery banding rats. We found that silencing H19 limits pathological RV hypertrophy, fibrosis and capillary rarefaction, thus preserving RV function in monocrotaline and pulmonary artery banding rats without affecting pulmonary vascular remodeling. This cardioprotective effect was accompanied by E2F transcription factor 1-mediated upregulation of enhancer of zeste homolog 2. In vitro, knockdown of H19 suppressed cardiomyocyte hypertrophy induced by phenylephrine, while its overexpression has the opposite effect. Finally, we demonstrated that circulating H19 levels in plasma discriminate PAH patients from controls, correlate with RV function and predict long-term survival in 2 independent idiopathic PAH cohorts. Moreover, H19 levels delineate subgroups of patients with differentiated prognosis when combined with the NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels or the risk score proposed by both REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) and the 2015 European Pulmonary Hypertension Guidelines.Our findings identify H19 as a new therapeutic target to impede the development of maladaptive RV remodeling and a promising biomarker of PAH severity and prognosis.
99mTc-Leukocyte Scintigraphy Revealed Viral Pulmonary Infection in a COVID-19 Patient
Authors: Jiefu Zheng, Yiyan Liu
Journal: Clinical Nuclear Medicine (2020)

Abstract 99m Tc-leukocyte scintigraphy was performed on a 40-year-old woman with spiking fevers. A focus of intense uptake in the right upper thorax was identified, concerning for infection along the central line in the superior vena cava. Additionally, heterogeneously increased uptake in both lungs was noted, which suggested pulmonary infection. CT images of the chest showed patchy ground-glass changes in both lungs and a large consolidation in the right lower lobe, which were consistent with changes for COVID-19 (coronavirus disease 2019). Severe acute respiratory syndrome coronavirus 2 RNA test was positive. This case demonstrates that leukocyte uptake in bilateral lungs could reveal viral pulmonary infection in COVID-19.
Doctors in England and Wales get 2.8% pay rise
Authors: Abi Rimmer
Journal: BMJ (2020)

Hospital doctors and salaried GPs in England will receive a 2.8% pay rise backdated to April this year, the Department of Health and Social Care has announced.

In Wales the pay rise extends more widely: consultants, specialty and associate specialist doctors, junior doctors, and salaried GPs will all receive a 2.8% increase.

The BMA expressed disappointment that the pay rise in England did not apply to all doctors. Hospital doctors in England will receive a 2.8% pay rise worth £2200-£3000 for consultants, £1100-£2100 for specialty doctors, and £1500-£2600 for associate specialists, …
Long-Term Functional Patency and Cost-Effectiveness of Arteriovenous Fistula Creation under Regional Anesthesia: a Randomized Controlled Trial
Authors: Emma Aitken, Rachel Kearns, Lucian Gaianu, Andrew Jackson, Mark Steven, John Kinsella, Marc Clancy, Alan Macfarlane
Journal: Journal of the American Society of Nephrology (2020)

Regional anesthesia improves short-term blood flow through arteriovenous fistulas (AVFs). We previously demonstrated that, compared with local anesthesia, regional anesthesia improves primary AVF patency at 3 months.To study the effects of regional versus local anesthesia on longer-term AVF patency, we performed an observer-blinded randomized controlled trial at three university hospitals in Glasgow, United Kingdom. We randomly assigned 126 patients undergoing primary radiocephalic or brachiocephalic AVF creation to receive regional anesthesia (brachial plexus block; 0.5% L-bupivacaine and 1.5% lidocaine with epinephrine) or local anesthesia (0.5% L-bupivacaine and 1% lidocaine). This report includes findings on primary, functional, and secondary patency at 12 months; reinterventions; and additional access procedures (primary outcome measures were previously reported). We analyzed data by intention to treat, and also performed cost-effectiveness analyses.At 12 months, we found higher primary patency among patients receiving regional versus local anesthesia (50 of 63 [79%] versus 37 of 63 [59%] patients; odds ratio [OR], 2.7; 95% confidence interval [95% CI], 1.6 to 3.8; P=0.02) as well as higher functional patency (43 of 63 [68%] versus 31 of 63 [49%] patients; OR, 2.1; 95% CI, 1.5 to 2.7; P=0.008). In 12 months, 21 revisional procedures, 53 new AVFs, and 50 temporary dialysis catheters were required. Regional anesthesia resulted in net savings of £195.10 (US$237.36) per patient at 1 year, and an incremental cost-effectiveness ratio of approximately £12,900 (US$15,694.20) per quality-adjusted life years over a 5-year time horizon. Results were robust after extensive sensitivity and scenario analyses.Compared with local anesthesia, regional anesthesia significantly improved both primary and functional AVF patency at 1 year and is cost-effective.Local Anaesthesia versus Regional Block for Arteriovenous Fistulae, NCT01706354.
Changes in titin phosphorylation and PKG activity underlie diastolic dysfunction at the cross-bridge level in the early stages of type 2 diabetes
Authors: MT Waddingham, N Hamdani, AJ Edgley, H Tsuchimochi, T Sonobe, DJ Kelly, N Yagi, WJ Paulus, M Shirai, JT Pearson
Journal: European Journal of Heart Failure (2018)
Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma
Authors: Eric Van Cutsem, Margaret A. Tempero, Darren Sigal, Do-Youn Oh, Nicola Fazio, Teresa Macarulla, Erika Hitre, Pascal Hammel, Andrew E. Hendifar, Susan E. Bates, Chung-Pin Li, Sunil R. Hingorani, Christelle de la Fouchardiere, Anup Kasi, Volker Heinemann, Anthony Maraveyas, Nathan Bahary, Laura Layos, Vaibhav Sahai, Lei Zheng, Jill Lacy, Joon Oh Park, Fabienne Portales, Paul Oberstein, Wilson Wu, Dimitrios Chondros, Andrea J. Bullock
Journal: Journal of Clinical Oncology (2020)

To evaluate the efficacy and safety of pegvorhyaluronidase alfa (PEGPH20) plus nab-paclitaxel/gemcitabine (AG) in patients with hyaluronan-high metastatic pancreatic ductal adenocarcinoma (PDA).HALO 109-301 was a phase III, randomized, double-blind, placebo-controlled study. Patients ≥ 18 years of age with untreated, metastatic, hyaluronan-high PDA were randomly assigned 2:1 to PEGPH20 plus AG or placebo plus AG. Treatment was administered intravenously in 4-week cycles (3 weeks on, 1 week off) until progression or intolerable adverse events: PEGPH20 3.0 µg/kg twice per week for cycle 1 and once per week thereafter; nab-paclitaxel 125 mg/m2 once per week; and gemcitabine 1,000 mg/m2 once per week. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Response was independently assessed per RECIST v1.1.At data cutoff, 494 patients were randomly assigned, with 492 (327 for PEGPH20 and 165 for placebo) included in intention-to-treat analyses. Baseline characteristics were balanced for PEGPH20 plus AG versus placebo plus AG. There were 330 deaths, with a median OS of 11.2 months for PEGPH20 plus AG versus 11.5 months for placebo plus AG (hazard ratio [HR], 1.00; 95% CI, 0.80 to 1.27; P = .97); median PFS was 7.1 months versus 7.1 months (HR, 0.97 [95% CI, 0.75 to 1.26]); ORR was 47% versus 36% (ORR ratio, 1.29 [95% CI, 1.03 to 1.63]). Grade ≥ 3 adverse events with a ≥ 2% higher rate with PEGPH20 plus AG than with placebo plus AG included fatigue (16.0% v 9.6%), muscle spasms (6.5% v 0.6%), and hyponatremia (8.0% v 3.8%).The addition of PEGPH20 to AG increased the ORR but did not improve OS or PFS. The safety profile of PEGPH20 plus AG was consistent with that found in previous studies. These results do not support additional development of PEGPH20 in metastatic PDA.
Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies
Authors: Yonghan He, Sajid Khan, Zhiguang Huo, Dongwen Lv, Xuan Zhang, Xingui Liu, Yaxia Yuan, Robert Hromas, Mingjiang Xu, Guangrong Zheng, Daohong Zhou
Journal: Journal of Hematology & Oncology (2020)

Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that utilize the ubiquitin proteasome system (UPS) to degrade proteins of interest (POI). PROTACs are potentially superior to conventional small molecule inhibitors (SMIs) because of their unique mechanism of action (MOA, i.e., degrading POI in a sub-stoichiometric manner), ability to target "undruggable" and mutant proteins, and improved target selectivity. Therefore, PROTACs have become an emerging technology for the development of novel targeted anticancer therapeutics. In fact, some of these reported PROTACs exhibit unprecedented efficacy and specificity in degrading various oncogenic proteins and have advanced to various stages of preclinical and clinical development for the treatment of cancer and hematologic malignancy. In this review, we systematically summarize the known PROTACs that have the potential to be used to treat various hematologic malignancies and discuss strategies to improve the safety of PROTACs for clinical application. Particularly, we propose to use the latest human pan-tissue single-cell RNA sequencing data to identify hematopoietic cell type-specific/selective E3 ligases to generate tumor-specific/selective PROTACs. These PROTACs have the potential to become safer therapeutics for hematologic malignancies because they can overcome some of the on-target toxicities of SMIs and PROTACs.
Baseline metabolic tumor volume as a strong predictive and prognostic biomarker in patients with non-small cell lung cancer treated with PD1 inhibitors: a prospective study
Authors: David Chardin, Marie Paquet, Renaud Schiappa, Jacques Darcourt, Caroline Bailleux, Michel Poudenx, Aurélie Sciazza, Marius Ilie, Jonathan Benzaquen, Nicolas Martin, Josiane Otto, Olivier Humbert
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Reliable predictive and prognostic markers are still lacking for patients treated with programmed death receptor 1 (PD1) inhibitors for non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic and predictive values of different baseline metabolic parameters, including metabolic tumor volume (MTV), from 18F-fluorodeoxyglucose positron emission tomography–computed tomography ( 18 F-FDG PET/CT) scans in patients with NSCLC treated with PD1 inhibitors. Methods Maximum and peak standardized uptake values, MTV and total lesion glycolysis (TLG), as well as clinical and biological parameters, were recorded in 75 prospectively included patients with NSCLC treated with PD1 inhibitors. Associations between these parameters and overall survival (OS) were evaluated as well as their accuracy to predict early treatment discontinuation (ETD). Results A high MTV and a high TLG were significantly associated with a lower OS (p&lt;0.001). The median OS in patients with MTV above the median (36.5 cm 3 ) was 10.5 months (95% CI: 6.2 to upper limit: unreached), while the median OS in patients with MTV below the median was not reached. Patients with no prior chemotherapy had a poorer OS than patients who had received prior systemic treatment (p=0.04). MTV and TLG could reliably predict ETD (area under the receiver operating characteristic curve=0.76, 95% CI: 0.65 to 0.87 and 0.72, 95% CI: 0.62 to 0.84, respectively). Conclusion MTV is a strong prognostic and predictive factor in patients with NSCLC treated with PD1 inhibitors and can be easily determined from routine 18 F-FDG PET/CT scans. MTV, could help to personalize immunotherapy and be used to stratify patients in future clinical studies.
Perfusion-guided sonopermeation of neuroblastoma: a novel strategy for monitoring and predicting liposomal doxorubicin uptake <i>in vivo</i>
Authors: Aditi Bellary, Arelly Villarreal, Rojin Eslami, Quincy J Undseth, Bianca Lec, Ann M Defnet, Naina Bagrodia, Jessica J Kandel, Mark A Borden, Sumbul Shaikh, Rajiv Chopra, Theodore W Laetsch, Lauren J Delaney, Colette M Shaw, John R Eisenbrey, Sonia L Hernandez, Shashank R Sirsi
Journal: Theranostics (2020)

Neuroblastoma (NB) is the most common extracranial solid tumor in infants and children, and imposes significant morbidity and mortality in this population. The aggressive chemoradiotherapy required to treat high-risk NB results in survival of less than 50%, yet is associated with significant long-term adverse effects in survivors. Boosting efficacy and reducing morbidity are therefore key goals of treatment for affected children. We hypothesize that these may be achieved by developing strategies that both focus and limit toxic therapies to the region of the tumor. One such strategy is the use of targeted image-guided drug delivery (IGDD), which is growing in popularity in personalized therapy to simultaneously improve on-target drug deposition and assess drug pharmacodynamics in individual patients. IGDD strategies can utilize a variety of imaging modalities and methods of actively targeting pharmaceutical drugs, however
Demethylase-independent function of JMJD2D as a novel antagonist of p53 to promote Liver Cancer initiation and progression
Authors: Ming Li, Yuan Deng, Minghui Zhuo, Hui Zhou, Xu Kong, Xiaogang Xia, Zhaojie Su, Qiang Chen, Peng Guo, Pingli Mo, Chundong Yu, Wengang Li
Journal: Theranostics (2020)

Background: As a histone demethylase, JMJD2D can enhance gene expression by specifically demethylating H3K9me2/3 and plays an important role in promoting colorectal cancer progression. However, its role in liver cancer remains unclear. Methods: The expression of JMJD2D was examined in human liver cancer specimens and non-tumorous liver tissues by immunohistochemical or immunoblot analysis. JMJD2D expression was knocked down in liver cancer cells using small hairpin RNAs, and cells were analyzed with Western blot, real-time PCR, cell viability, colony formation, and flow cytometry assays. Cells were also grown as tumor xenografts in nude mice, and the tumor cell proliferation and apoptosis were measured by immunohistochemical analysis. The relationship between JMJD2D and p53 was studied by co-immunoprecipitation, chromatin immunoprecipitation, and electric mobility shift assay. Wild-type and JMJD2D-knockout mice were intraperitoneally injected with diethylnitrosamine (DEN) to induce liver tumors and the liver cancer initiation and progression were investigated. Results: JMJD2D was frequently upregulated in human liver cancer specimens compared with non-tumorous liver tissues. The overall survival of liver cancer patients with high JMJD2D expression was significantly decreased compared to that with low JMJD2D expression. JMJD2D knockdown reduced liver cancer cell proliferation and xenograft tumor growth, sensitized cells to chemotherapeutic drug-induced apoptosis, and increased the expression of cell cycle inhibitor p21 and pro-apoptosis gene PUMA. Genetically, JMJD2D deficiency protected mice against DEN-induced liver cancer initiation and progression. Knockout of tumor suppressor p53 significantly reduced the effects of JMJD2D knockdown on cell proliferation, apoptosis, and the expression of p21 and PUMA, suggesting that JMJD2D regulates liver cancer cell functions in part through inhibiting p53 signaling pathway. Mechanistically, JMJD2D directly interacted with p53 and inhibited p53 recruitment to the p21 and PUMA promoters in a demethylation activity-independent manner, implicating a demethylase-independent function of JMJD2D as a novel p53 antagonist. In addition, JMJD2D could activate Wnt/β-catenin signaling to promote liver cancer cell proliferation. Conclusion: Our study demonstrates that JMJD2D can antagonize the tumor suppressor p53 and activate an oncogenic signaling pathway (such as Wnt/β-catenin signaling pathway) simultaneously to promote liver cancer initiation and progression, suggesting that JMJD2D may serve as a novel target for liver cancer treatment.
How to move beyond quality improvement projects
Authors: Amar Shah
Journal: BMJ (2020)

### What you need to know

In recent years we have seen a proliferation in the interest and use of quality improvement in health and healthcare. This represents a promising shift in our mental models about how to solve some of our most complex quality issues. Alongside the increasing use of the word “improvement” in our everyday language within healthcare, there are differences in understanding of what exactly we mean by the term “quality improvement.” This article explores the difference between quality improvement and a quality management system, by defining quality improvement and describing how to best use quality improvement alongside control, assurance, and planning as part of a more holistic management system focused on quality.

Quality improvement should be seen as part of an overall system of quality management. Quality improvement is a systematic and applied approach to solving a complex issue, through testing and learning, measuring as you go, and deeply involving those closest to the issue in the improvement process.1 Anyone who has undertaken quality improvement work will testify that it is not easy—you are generally tackling a problem to which we do not know the solution, and where part of the answer is about behaviours, and hearts and minds. Quality improvement can be used to reduce unwarranted variation, reliably implement interventions that have been shown to improve outcomes, or discover new solutions through a process of innovation. As we are looking to learn whether a particular service or issue has improved, the process also …
The Problem of Daily Imaging in the Intensive Care Unit
Authors: Christopher G. Choukalas, Thanh-Giang Vu
Journal: JAMA Internal Medicine (2020)

As the economic and clinical fragilities of the world make themselves known during the coronavirus disease 2019 (COVID-19) pandemic, the importance of resource use rises to the forefront of health care professionals' minds  The authors look on the compelling example by Maley and Stevens regarding a case where routine diagnostic examinations turned into a near-miss event  They argue that not only are seemingly innocuous care practices, such as daily chest radiographs (CXRs), expensive and inefficient, but also that significant underappreciated harms, including inappropriate interventions based on inaccurate results, abound  A systematic review of 9 studies also revealed no harm associated with a restrictive CXR strategy  A study of an intervention to reduce routine CXRs in a cardiac surgery ICU showed similar results: nearly 11% of patients had unexpected, clinically relevant findings discovered on routine CXRs,4 although clinical outcomes were not affected  Furthermore, the bottom line seems to be that it is possible to reduce routine CXRs in the ICU, and although a few findings might be missed, it does not seem to alter patients' outcomes
Dark pigmented lesions: Diagnostic accuracy of dermoscopy and reflectance confocal microscopy in a tertiary referral center for skin cancer diagnosis
Authors: Caterina Longo, Mauro Mazzeo, Margherita Raucci, Luigi Cornacchia, Michela Lai, Luca Bianchi, Ketty Peris, Riccardo Pampena, Giovanni Pellacani
Journal: Journal of the American Academy of Dermatology (2020)