tbuckley/cabot-search huggingface dataset:
Consultant who signed cremation forms without examining the bodies is struck off
Authors: Clare Dyer
Journal: BMJ (2020)

A former consultant in acute medicine who signed hundreds of cremation forms without examining the bodies, as required by law, has been struck off the UK medical register.

Over a four and a half year period at Stepping Hill Hospital in Stockport Brian Cheadle signed around 485 forms authorising cremation without viewing the body, despite declaring on the cremation form that he had, investigators found.

In October 2018 he pleaded guilty and was convicted at Manchester Crown Court of making a false representation with a view to procuring the burning of human remains and was given a 12 month conditional discharge. The forms in question, part of a process introduced …
SURG-06. AWAKE CRANIOTOMY FOR BRAIN TUMOR IN PEDIATRIC PATIENTS
Authors: Carlos Almeida, Alessandra Levy Antoniazzi, Bruna Minniti Mançano, Marcus Matsushita, Rachel Eggers Bacci, Danielli Basso, Lucas Dias Lourenço
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The challenge of surgery in neurooncology is to achieve the maximum extent of resection while preserving eloquent functions. Intra-operative cortical mapping during resection of a brain tumor allows direct stimulation in eloquent areas with a reduction in postoperative deficits. This procedure has been performed in adults and children down to the age of 11 years. There are only two cases reported on the literature of an 8-year-old and 9-year-old child submitted to an awake craniotomy for brain tumor resection. Pediatric patients are prone to more risks than adults because they become easily agitated after pain sensation. Extensive preparation for the procedure is essential for pediatric patients in order to avoid a lack of cooperation. CASE PRESENTATION: Two patients, with 9-year-old presented with seizures due to a tumor in the left temporoparietal region. In order to identify language and motor–controlling areas during resection, we proposed an awake craniotomy. Because of their ages, they were prepared by a multidisciplinary team. The children’s cooperation during the mapping procedure and tumor resection were exceptional. Postoperative cranial MRI confirmed partial resection of the lesion, whose remnant was located in the left motor area. No seizures occurred during the postoperative period, and both were discharged without a neurological disability on the fifth day after the surgery. Histology revealed a dysembryoplastic neuroepithelial tumor (WHO grade I). CONCLUSION Brain mapping during resection of a tumor in an awake pediatric patient is feasible and can be safely performed even in patients under 11-year-old.
Use of Metformin and Cardiovascular Effects of New Classes of Glucose-Lowering Agents: A Meta-analysis of Cardiovascular Outcome Trials in Type 2 Diabetes
Authors: Francesco Zaccardi, David E. Kloecker, John B. Buse, Chantal Mathieu, Kamlesh Khunti, Melanie J. Davies
Journal: Diabetes Care (2020)

Over the last two decades, the large majority of clinical guidelines on the treatment of hyperglycemia in subjects with type 2 diabetes have suggested metformin as the first-line glucose-lowering treatment alongside lifestyle changes to reach personalized glycemic targets. Recently, the European Society of Cardiology recommended using glucagon-like peptide 1 receptor agonists (GLP-1RA) or sodium–glucose cotransporter 2 inhibitors (SGLT-2i) as first-line glucose-lowering therapy in subjects with type 2 diabetes at high or very high risk of cardiovascular disease, ahead of metformin treatment, to reduce cardiovascular events (1).

Following the European Society of Cardiology guidelines, several analyses have investigated whether the cardiovascular effects of GLP-1RA or SGLT-2i would differ in relation to the use of metformin. Some of these studies reported a “statistically significant” difference (i.e., interaction) in the cardiovascular effects of SGLT-2is, whereby subjects with metformin have a lower cardiovascular protection from SGLT-2i, leading to several hypotheses about the possible pharmacological mechanisms. Interpreting interaction results, however, may be difficult, as they suffer from well-known drawbacks, including limited statistical power (2). For overcoming this problem and identifying who may be most likely to benefit from a specific treatment, trial-specific interactions may be combined with a meta-analytical approach (3).

In this study, we systematically investigated the differences in the treatment effect of incretins (GLP-1RA and dipeptidyl peptidase 4 inhibitors [DPP-4i]) and SGLT-2i on cardiovascular outcomes according to metformin use. We included DPP-4i given their overlapping pharmacodynamics with GLP-1RAs and the previous evidence of interactions with metformin (4).

On 5 October 2020, we searched for randomized controlled trials (RCTs) in adults with type 2 diabetes reporting incretin or SGLT-2i treatment effect for the primary cardiovascular outcome (major adverse cardiovascular event [MACE]) stratified by baseline metformin use; details of the search, included trials, and risk of bias are available on request. We …
Abstract 15678: Multi-Level and Multifactorial Barriers to Implementation of Guideline Directed Syncope Care Substantially Increases Resource Utilization With Dramatic Impact on Potential Cost
Authors: Vedant Gupta, Amy Cowley, Hilary Surratt, Susan S Smyth, Matthew Sirrine, Hanwen Yuan, Jing Li
Journal: Circulation (2019)

Introduction: Syncope is a common reason for ED visits and costs over $20 billion annually in the US. Recent guidelines published in 2017 focused on high value testing, but the effect on implementa...
PATH-18. HIGH-GRADE NEUROEPITHELIAL TUMOR (HGNET) IN A PEDIATRIC CASE-SERIES
Authors: Felipe Hada Sanders, Alessandra Azambuja, Fernando Frasseto, Sergio Rosemberg, Hamilton Matushita
Journal: Neuro-Oncology (2020)

Abstract The central nervous system (CNS) high-grade neuroepithelial tumor is a recently described molecular entity. We report 2 new CNS HGNET cases sharing common clinical presentation and pathologic features. In summary, CNS HGNET represents a rare tumor occurring in young patients with dismal prognosis. We think it is important to report these cases to spread the experience and raise the knowledge of the medical community.
DDRE-23. THE COMBINATION PARP INHIBITOR OLAPARIB WITH TEMOZOLOMIDE IN AN EXPERIMENTAL GLIOBLASTOMA MODEL
Authors: Kihwan Hwang, Kyeong-O Go, Sang Ho Kim, Hyunwoo Lee, Jung Ho Han, Chae-Yong Kim
Journal: Neuro-Oncology (2020)

Abstract Poly (ADP-ribose) polymerase (PARP) inhibition could enhance the efficacy of temozolomide and prolong survival in patients with glioblastoma. The aim of this study was to evaluate the combination of the PARP inhibitor olaparib with temozolomide in the treatment of glioblastoma by evaluating in vitro and in vivo antitumor effects in an experimental glioblastoma model. The authors investigated antitumor effects of olaparib on temozolomide-induced cytotoxicity on O6-methylguanine methyltransferase (MGMT) promotor methylated (U87MG, U251MG) and MGMT promotor unmethylated (T98G) glioblastoma cell lines using in vitro cell viability and apoptosis assay. We found that the combination of olaparib with temozolomide enhanced temozolomide-induced cytotoxicity in all glioblastoma cell lines regardless of the status of MGMT promotor methylation. For in vivo studies, nude mice bearing orthotopically xenografted glioblastoma cell lines (U87MG) were randomized to four experimental groups: (i) untreated, (ii) temozolomide alone, (iii) olaprib alone and, (iv) olaparib+temozolomide. Mice were treated daily for 4 weeks and monitored for tumor growth, and survival. However, the addition of olaparib had no impact on the efficacy of temozolomide. The combination of PARP inhibitor olaparib with temozolomide could be an effective therapeutic approach for treatment of glioblastoma regardless of MGMT promotor methylation status, although the efficacy still should be evaluated by in vivo and clinical studies.
47P Radiological patterns of tumour progression in patients treated with a combination of immune checkpoint blockers and antiangiogenic drugs
Authors: E. Guiard, C. Baldini, C. Pobel, P. Martin-Romano, S. Champiat, A. Hollebecque, S. Postel-Vinay, A. Varga, R. Bahleda, A. Gazzah, L. Verlingue, A. Geraud, M. Ningarhari, E. Angevin, J-M. Michot, V. Ribrag, A. Marabelle, J-C. Soria, C. Massard, S. Ammari
Journal: Annals of Oncology (2020)
Implantable Cisplatin Synthesis Microdevice for Regional Chemotherapy
Authors: Rebecca Campbell, Hyunji Shim, Je Choi, Moonchul Park, Eunjeong Byun, Sayemul Islam, Seung Hyun Song, Albert Kim
Journal: Advanced Healthcare Materials (2020)

Abstract Cisplatin, the first platinum chemotherapy agent to obtain Food and Drug Administration (FDA) approval in 1978, is widely used for a number of cancers. However, the painful side effects stemming from systemic delivery are the inevitable limitation of cisplatin. A possible solution is regional chemotherapy using various drug delivery systems, which reduces the systemic toxicity and increases drug accumulation in the tumor. In this paper, a rice‐grain sized, ultrasonically powered, and implantable microdevice that can synthesize cisplatin in situ is presented. The microdevice produces 0.7 mg of cisplatin within 1 h under ultrasonic irradiation (400 mW cm −2 ). The effect of the microdevice‐synthesized cisplatin is evaluated using in vitro murine breast cancer cells and ex vivo liver tissue. The results suggest that cytotoxic activities of the microdevice‐mediated cisplatin delivery are significantly higher in both in vitro and ex vivo experiments. Overall, the proposed cisplatin synthesis microdevice represents a strong alternative treatment option for regional chemotherapy
Identification and Characterization of Plasmin-Independent Thrombolytic Enzymes
Authors: Md. Mehedi Hassan, Shirina Sharmin, Hyeon-Jin Kim, Seong-Tshool Hong
Journal: Circulation Research (2020)

Rationale: Current thrombolytic agents activate plasminogen to plasmin which triggers fibrinolysis to dissolve thrombi. Since plasmin is a nonspecific proteolytic enzyme, all of the current plasmin-dependent thrombolytics lead to serious hemorrhagic complications, demanding a new class of fibrinolytic enzymes independent from plasmin activation and undesirable side effects. We speculated that the mammalian version of bacterial heat-shock proteins could selectively degrade intravascular thrombi, a typical example of a highly aggregated protein mixture. Objective: The objective of this study is to identify enzymes that can dissolve intravascular thrombi specifically without affecting fibrinogen and fibronectin so that the wound healing processes remain uninterrupted and tissues are not damaged. In this study, HtrA (high-temperature requirement A) proteins were tested for its specific proteolytic activity on intravascular thrombi independently from plasmin activation. Methods and Results: HtrA1 and HtrA2/Omi proteins, collectively called as HtrAs, lysed ex vivo blood thrombi by degrading fibrin polymers. The thrombolysis by HtrAs was plasmin-independent and specific to vascular thrombi without causing the systemic activation of plasminogen and preventing nonspecific proteolysis of other proteins including fibrinogen and fibronectin. As expected, HtrAs did not disturb clotting and wound healing of excised wounds from mouse skin. It was further confirmed in a tail bleeding and a rebleeding assay that HtrAs allowed normal clotting and maintenance of clot stability in wounds, unlike other thrombolytics. Most importantly, HtrAs completely dissolved blood thrombi in tail thrombosis mice, and the intravenous injection of HtrAs to mice with pulmonary embolism completely dissolved intravascular thrombi and thus rescued thromboembolism. Conclusions: Here, we identified HtrA1 and HtrA2/Omi as plasmin-independent and highly specific thrombolytics that can dissolve intravascular thrombi specifically without bleeding risk. This work is the first report of a plasmin-independent thrombolytic pathway, providing HtrA1 and HtrA2/Omi as ideal therapeutic candidates for various thrombotic diseases without hemorrhagic complications.
Coronary CT Angiography and Comparative Effectiveness Research: Prognostic Value of Atherosclerotic Disease Burden in Appropriately Indicated Clinical Examinations⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Paul Schoenhagen, Rory Hachamovitch, Stephan Achenbach
Journal: JACC. Cardiovascular imaging (2011)
Thresholds for Neonatal Hypoglycemia in Clinical Settings
Authors: Alessandro Perri, Maria Letizia Patti, Giovanni Vento
Journal: JAMA Pediatrics (2020)

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RONC-32. LOCAL CONTROL FOLLOWING PROTON THERAPY FOR PEDIATRIC CHORDOMA
Authors: Daniel Indelicato, Ronny Rotondo, Raymond Vega, Adam Holtzman, Wen Shen Looi, Christopher Morris, Eric Sandler, Philipp Aldana, Julie Bradley
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Due to the location and high dose required for disease control, pediatric chordomas are theoretically well-suited for treatment with proton therapy, but their low incidence limits the clinical outcome data available in the literature. METHODS AND MATERIALS: Between 2008 and 2019, 29 patients with a median age of 14.8 years (range, 3.8–21.8) received proton therapy for non-metastatic chordoma at a single institution. Twenty-four tumors arose in the clivus/cervical spine region and 5 in the lumbosacral spine. Twenty-six tumors demonstrated well-differentiated histology and 3 were dedifferentiated or not otherwise specified (NOS). Approximately half of the tumors underwent specialized testing: 14 were brachyury-positive and 10 retained INI-1. Seventeen patients had gross disease at the time of radiation. The median radiation dose was 73.8 GyRBE. RESULTS With a median follow-up of 4.3 years (range, 1.0–10.7), the 5-year estimates of local control, progression-free survival, and overall survival rates were 85%, 82%, and 86%, respectively. Excluding 3 patients with dedifferentiated/NOS chordoma, the 5-year local control, progression-free survival, and overall survival rates were 92%, 92%, and 91%, respectively. Serious toxicities included 3 patients with hardware failure or related infection requiring revision surgery, 2 patients with hormone deficiency, and 2 patients with Eustachian tube dysfunction causing chronic otitis media. CONCLUSION In pediatric patients with chordoma, proton therapy is associated with a low risk of serious toxicity and high efficacy, particularly in well-differentiated tumors. Complete resection may be unnecessary for local control and destabilizing operations requiring instrumentation may result in additional complications following therapy.
Abstract P116: Chronic Kidney Disease And Cardiac Arrhythmias: A Systematic Review and Meta-analysis
Authors: Esther D Kim, Ning Ding, Junichi Ishigami, Xuejuan Ning, Yijing Feng, Josef Coresh, Lin Y Chen, Kunihiro Matsushita
Journal: Circulation (2020)

Background: Chronic kidney disease (CKD) strongly predicts sudden cardiac death and may elevate the risk of certain cardiac arrhythmias like atrial fibrillation; however, the relationships between CKD and various types of arrhythmia are not well-characterized. Methods: We performed a systematic review and meta-analysis by searching Embase and PubMed for prospective, cross-sectional, and case-control studies examining the associations of two key CKD measures, estimated glomerular filtration rate (eGFR) and albuminuria, with arrhythmias in adults that were published until July 2018. We performed qualitative assessment of studies using the Newcastle Ottawa Quality Assessment Scale. We pooled the results using random-effects models. Results: Among 16,245 articles, we identified 34 prospective (n=24,213,233), 21 cross-sectional (n=253,328), and 4 case-control (n=1,694) studies that included diverse study populations from 19 countries and were mostly high quality. Most prospective studies examined the relationship between eGFR and atrial fibrillation (AF), and demonstrated that lower eGFR was associated with a higher risk of AF (pooled hazard ratio [HR] 1.72 [95% CI: 1.30, 2.27] comparing reduced vs. referent eGFR groups)[ Figure ]. A few studies examined albuminuria and demonstrated its associations with AF (pooled HR 2.16 [95% CI: 1.74, 2.67] comparing high vs. low albuminuria). Results were similar for cross-sectional studies. Four prospective studies reported a higher incidence of ventricular tachycardia resulting in ICD shock according to reduced eGFR (pooled HR 2.32 [95% CI: 1.74, 3.09] comparing reduced vs. referent eGFR groups). Limited number of studies examined other types of arrhythmia. Conclusion: We identified robust data on the relationship between CKD (eGFR and albuminuria) and AF. Reduced eGFR was associated with life-threatening ventricular arrhythmias. Our review highlights the need of future studies for non-AF arrhythmias, especially in the context of albuminuria.
RONC-31. ADVANCED ECHOCARDIOGRAPHY WITH MYOCARDIAL-STRAIN-ANALYSIS DESCRIBES SUBCLINICAL CARDIAC DYSFUNCTION AFTER CRANIOSPINAL IRRADIATION (CSI) IN PEDIATRIC AND YOUNG ADULT PATIENTS WITH CENTRAL NERVOUS SYSTEM (CNS) TUMORS
Authors: Hugo Martinez, Ralph Salloum, Erin Wright, Philip Khoury, Justin Tretter, Thomas Ryan
Journal: Neuro-Oncology (2020)

Abstract CSI is part of the treatment of CNS tumors and is associated with cardiovascular disease; data in pediatric/young-adult patients are limited. Myocardial-strain-analysis can reveal subclinical dysfunction. Retrospective, single-center study in CNS tumor patients managed with CSI from 1986–2018. Clinical details, and echocardiography including myocardial-strain-analysis were collected at T1=first echocardiogram after CSI, and T2=most recent echocardiogram. Data are mean±standard deviation. Echocardiograms were available in 44 patients (36%female, 14±8.0years) at T1 and 39 patients (38%female, 21.0±11.3years) at T2. Standard echocardiography was normal for all subjects. At T1, global longitudinal peak systolic strain (GLS) was -16.3%±3.7% in CSI vs. -21.6%±3.5% in controls (p&amp;lt;0.0001); global radial peak systolic strain (GRS) was 21.5%±10.1% in CSI vs. 26.5%±7.4% in controls, and global circumferential peak systolic strain (GCS) was -19.5%±6.0% in CSI vs. -21.4%±3.4% in controls (p&amp;lt;0.05, both comparisons). At T2, GLS was -15.8%±5.2% in CSI vs. -21.9±3.5% in controls (p&amp;lt;0.0001); GRS was 22.6%±10.4% in CSI vs. 27.1±8.2% in controls (p&amp;lt;0.05); GCS was -20.5%±6.9% in CSI vs. -21.8±3.5% in controls (p=0.10). For 17 patients with myocardial-strain-analysis available for both time points: difference in GLS was 0.06±7.2% (p&amp;gt;0.95); GRS was 5.5±9.5% (p&amp;lt;0.05); GCS was -3.4±4.9% (p&amp;lt;0.05). Subclinical dysfunction is present at first echocardiogram after CSI. Myocardial impairment may recover with time, however further analysis is needed to identify risk factors and trends. These results argue for inclusion of baseline cardiovascular assessment and longitudinal follow-up in CNS tumor patients post CSI.
M2 microglial small extracellular vesicles reduce glial scar formation <i>via</i> the miR-124/STAT3 pathway after ischemic stroke in mice
Authors: Zongwei Li, Yaying Song, Tingting He, Ruoxue Wen, Yongfang Li, Tingting Chen, Shuxian Huang, Yongting Wang, Yaohui Tang, FanXia Shen, Heng-Li Tian, Guo-Yuan Yang, Zhijun Zhang
Journal: Theranostics (2020)

Rationale: Glial scars present a major obstacle for neuronal regeneration after stroke. Thus, approaches to promote their degradation and inhibit their formation are beneficial for stroke recovery. The interaction of microglia and astrocytes is known to be involved in glial scar formation after stroke; however, how microglia affect glial scar formation remains unclear. Methods: Mice were treated daily with M2 microglial small extracellular vesicles through tail intravenous injections from day 1 to day 7 after middle cerebral artery occlusion. Glial scar, infarct volume, neurological score were detected after ischemia. microRNA and related protein were examined in peri-infarct areas of the brain following ischemia. Results: M2 microglial small extracellular vesicles reduced glial scar formation and promoted recovery after stroke and were enriched in miR-124. Furthermore, M2 microglial small extracellular vesicle treatment decreased the expression of the astrocyte proliferation gene signal transducer and activator of transcription 3, one of the targets of miR-124, and glial fibrillary acidic protein and inhibited astrocyte proliferation both in vitro and in vivo. It also decreased Notch 1 expression and increased Sox2 expression in astrocytes, which suggested that astrocytes had transformed into neuronal progenitor cells. Finally, miR-124 knockdown in M2 microglial small extracellular vesicles blocked their effects on glial scars and stroke recovery. Conclusions: Our results showed, for the first time, that microglia regulate glial scar formation via small extracellular vesicles, indicating that M2 microglial small extracellular vesicles could represent a new therapeutic approach for stroke.