tbuckley/cabot-search huggingface dataset:
Consensus recommendations for a standardized brain tumor imaging protocol for clinical trials in brain metastases
Authors: Timothy J Kaufmann, Marion Smits, Jerrold Boxerman, Raymond Huang, Daniel P Barboriak, Michael Weller, Caroline Chung, Christina Tsien, Paul D Brown, Lalitha Shankar, Evanthia Galanis, Elizabeth Gerstner, Martin J van den Bent, Terry C Burns, Ian F Parney, Gavin Dunn, Priscilla K Brastianos, Nancy U Lin, Patrick Y Wen, Benjamin M Ellingson
Journal: Neuro-Oncology (2020)

A recent meeting was held on March 22, 2019, among the FDA, clinical scientists, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocacy groups to discuss challenges and potential solutions for increasing development of therapeutics for central nervous system metastases. A key issue identified at this meeting was the need for consistent tumor measurement for reliable tumor response assessment, including the first step of standardized image acquisition with an MRI protocol that could be implemented in multicenter studies aimed at testing new therapeutics. This document builds upon previous consensus recommendations for a standardized brain tumor imaging protocol (BTIP) in high-grade gliomas and defines a protocol for brain metastases (BTIP-BM) that addresses unique challenges associated with assessment of CNS metastases. The "minimum standard" recommended pulse sequences include: (i) parameter matched pre- and post-contrast inversion recovery (IR)-prepared, isotropic 3D T1-weighted gradient echo (IR-GRE); (ii) axial 2D T2-weighted turbo spin echo acquired after injection of gadolinium-based contrast agent and before post-contrast 3D T1-weighted images; (iii) axial 2D or 3D T2-weighted fluid attenuated inversion recovery; (iv) axial 2D, 3-directional diffusion-weighted images; and (v) post-contrast 2D T1-weighted spin echo images for increased lesion conspicuity. Recommended sequence parameters are provided for both 1.5T and 3T MR systems. An "ideal" protocol is also provided, which replaces IR-GRE with 3D TSE T1-weighted imaging pre- and post-gadolinium, and is best performed at 3T, for which dynamic susceptibility contrast perfusion is included. Recommended perfusion parameters are given.
Imaging of macrophage mitochondria dynamics <i>in vivo</i> reveals cellular activation phenotype for diagnosis
Authors: Yue Li, Yuan He, Kai Miao, Ying Zheng, Chuxia Deng, Tzu-Ming Liu
Journal: Theranostics (2020)

Highly plastic macrophages are pivotal players in the body's homeostasis and pathogenesis. Grasping the molecular or cellular factors that drive and support the macrophage activation will help to develop diagnostics and manipulate their functions in these contexts. However, the lack of in vivo characterization methods to reveal the dynamic activation of macrophages impedes these studies in various disease contexts. Methods: Here, in vitro bone marrow-derived macrophages (BMDMs) and in vivo Matrigel plug were used to evaluate how mitochondria dynamics supports cellular activation and functions. We conducted macrophage repolarization in vitro to track mitochondria dynamics during the shift of activation status. For in vivo diagnosis, a novel MitoTracker-loaded liposome was first developed to label macrophage mitochondria in mice before/after inflammatory stimulation. Results: Based on the typical activation of in vitro BMDMs, we found glycolysis based macrophages have punctate and discrete mitochondria, while OXPHOS active macrophages have elongated and interconnected mitochondria. M1, M2a, M2b, and M2c activated BMDMs showed clustered and differentiable features in mitochondrial morphology. These features also hold for Matrigel plug-recruited macrophages in mice. Furthermore, with the interventions on M2a macrophages in vitro, we demonstrated that mitochondria morphology could be a metabolic index to evaluate macrophage activation status under drug manipulation. Using the MitoTracker-loaded liposomes, we further achieved subcellular imaging of macrophage mitochondria in vivo. Their organization dynamics revealed the dynamic change from anti-inflammatory macrophages to inflammatory ones in vivo under the lipopolysaccharide (LPS) challenge. Conclusion: These results reveal that subcellular imaging of mitochondria organization can characterize the activation status of macrophage in vitro and in vivo at a single-cell level, which is critical for the studies of noninvasive diagnosis and therapeutic drug monitoring.
PB2293 PEGFILGRASTIM VERSUS FILGRASTIM IN THE MANAGEMENT OF THERAPY‐RELATED NEUTROPENIA IN RELAPSED AND REFRACTORY MULTIPLE MYELOMA IN TREATMENT WITH POMALIDOMIDE‐DEXAMETHASONE
Authors: C. Cerchione, G. Martinelli, D. Nappi, A. E. Pareto, F. Pane, L. Catalano
Journal: HemaSphere (2019)

Background: Pegfilgrastim is a pegylated long‐acting recombinant form of G‐CSF that extends the half‐life and allows for once‐per‐cycle dosing, requiring less frequent dosing than nonpegylated G‐CSF. Aims: The objective of this study was to compare the efficacy and safety of pegfilgrastim in patients affected by heavily pretreated MM, treated with pomalidomide‐dexamethasone, in order to determine whether a single subcutaneous injection of pegfilgrastim is as effective as daily injections of standard filgrastim, in terms of haematological toxicity, febrile neutropenic episodes, antibiotic usage and hospedalization duration. Methods: We enrolled 33 patients (19 male and 14 female) median age at diagnosis 69 years (r. 52‐84), and median age at start of treatment 76 years (r.56‐90) treated with several lines of treatments (median 7, r. 2‐11), every refractory to all the drugs previously received, received Pomalidomide‐Dexamethasone (Pomalidomide 4 mg for 21 days, Dexamethasone 40 mg days 1,8,15,22, pegfilgrastim day +8) every 28 days, until progression. Results: Since first course, received in domestic setting, with a very good compliance, patients performed blood counts once weekly and received, from day +8 to day +19 (“day + 1” when the protocol starts), prophylactic oral chinolonic antibiotics and anti‐fungal drugs. During neutropenia after first cycle, Filgrastim (5 μgr/kg/day for 3 days) was given if neutrophils count was &lt;1500 × 10^9 cells/L. Median number of filgrastim administrations was 4.8 (r. 3‐6); nadir neutropenia was registered after a median of 10.7 days (r. 7‐14); median of nadir neutrophil count was 1.17 × 10^9 cells/L (range 0.3 – 1.5 × 10^9 cells/L), with maximum duration of 14 days. From the second course, all patients switched to prophylaxis with pegfilgrastim (6 mg), injected subcutaneously with a single administration on day +3 independently from the neutrophil count at that time. During pegfilgrastim, neutropenia was never longer than 8 days, with a consequent reduction of neutropenia‐related infections. Median nadir neutrophil count, evaluated for every patients for at least three courses of therapy (r. 3‐6) registered at day +11, was 1.39 (range 0.9‐2.2 × 10^9 cells/L). Only 4 patients needed a supplement of 3 administrations of filgrastim. Pegfilgrastim was well tolerated in all patients: main side effects in our patients were mild fever and bone pain (21.2%). Summary/Conclusion: In conclusions, in patients affected by heavily pretreated MM treated with pomalidomide‐dexamethasone, pegfilgrastim seems to reduce the incidence of severe neutropenia and infections and may increase the possibility to maintain the scheduled time of treatment.
Ticagrelor With or Without Aspirin After PCI: The TWILIGHT Platelet Substudy
Authors: Usman Baber, M. Urooj Zafar, George Dangas, Ginés Escolar, Dominick J. Angiolillo, Samin K. Sharma, Annapoorna S. Kini, Samantha Sartori, Lauren Joyce, Birgit Vogel, Serdar Farhan, Paul Gurbel, C. Michael Gibson, Valentin Fuster, Roxana Mehran, Juan J. Badimon
Journal: Journal of the American College of Cardiology (2020)
Clinicopathological Features, Staging, and Current Approaches to Treatment in High-Risk Resectable Melanoma
Authors: Emily Z Keung, Jeffrey E Gershenwald
Journal: JNCI Journal of the National Cancer Institute (2020)

The incidence of melanoma in the United States has been increasing over the past several decades. Prognosis largely depends on disease stage, with 5-year melanoma-specific survival ranging from as high as 99% in patients with stage I disease to less than 10% for some patients with stage IV (distant metastatic) disease. Fortunately, in the last 5-10 years, there have been remarkable treatment advances for patients with high-risk resectable melanoma, including approval of targeted and immune checkpoint blockade therapies. In addition, results of recent clinical trials have confirmed the importance of sentinel lymph node biopsy and continue to refine the approach to regional lymph node basin management. Lastly, the melanoma staging system was revised in the eighth edition AJCC Cancer Staging Manual, which was implemented on January 1, 2018. Here we discuss these changes and the clinicopathological features that confer high risk for locoregional and distant disease relapse and poor survival. Implications regarding the management of melanoma in the metastatic and adjuvant settings are discussed, as are future directions for neoadjuvant therapies.
The interferon‐γ‐induced protein 10/CXCR3 axis is associated with human herpesvirus‐6 reactivation and the development of sequelae in drug reaction with eosinophilia and systemic symptoms*
Authors: C.‐W. Yang, Y.‐T. Cho, Y.‐C. Hsieh, S.‐H. Hsu, K.‐L. Chen, C.‐Y. Chu
Journal: British Journal of Dermatology (2020)

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a condition caused by a drug-induced immune response. Previous reports have found that CXCL10, also known as interferon-γ-induced protein (IP)-10, may participate in the pathogenesis of cutaneous adverse drug reactions. However, the exact role of IP-10 in DRESS and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) has remained unknown.This comparative prospective cohort study aimed to ascertain the roles of the IP-10/CXCR3 axis in DRESS and SJS/TEN.Plasma IP-10 levels were analysed, and univariate analyses were conducted to assess the relationship between IP-10, human herpesvirus (HHV)-6 reactivation and the development of long-term sequelae. We also performed immunohistochemical staining using skin specimens and flow cytometry to determine the expression of CXCR3 in peripheral blood mononuclear cells (PBMCs).Significantly higher plasma IP-10 levels were observed in patients with DRESS with long-term sequelae (effect size 0·81) and also in those with HHV-6 reactivation (effect size 0·83). By immunohistochemistry, more abundant IP-10+ and CXCR3+ cells were demonstrated in the skin lesions of patients with DRESS with HHV-6 reactivation. The percentages of CLA+ CXCR3+ CD4+ cells and CLA+ CXCR3+ CD8+ cells were also higher in the PBMCs of HHV-6-reactivated patients with DRESS than in those of patients with SJS/TEN.Higher plasma IP-10 levels are associated with the development of long-term sequelae in DRESS. Higher IP-10/CXCR3 expression in skin and more abundant CLA+ CXCR3+ CD4+ cells and CLA+ CXCR3+ CD8+ cells were observed in patients with DRESS with HHV-6 reactivation. The IP-10/CXCR3 axis is associated with HHV-6 reactivation and development of long-term sequelae in DRESS. What is already known about this topic? Elevated levels of interferon-γ-induced protein-10 (IP-10) have been observed in patients with drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Patients with DRESS tend to develop long-term autoimmune sequelae, including type 1 diabetes and autoimmune thyroiditis. IP-10 has been associated with these autoimmune diseases in previous studies. What does this study add? The patients with DRESS with HHV-6 reactivation exhibited higher levels of IP-10 in the plasma and skin than the patients with DRESS without HHV-6 reactivation and the patients with SJS/TEN. Patients with DRESS with higher plasma IP-10 levels tended to develop sequelae during long-term follow-up. What is the translational message? IP-10 is a useful biomarker to predict the development of long-term sequelae in patients with DRESS. Linked Comment: Belloón and Kardaun. Br J Dermatol 2020; 183:804-805.
Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build Trust
Authors: Quinn Bott
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 February 2020Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build TrustFREEQuinn BottQuinn BottUniformed Services University of Health Services, Bethesda, Maryland (Q.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W20-0010 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build Trust "Voices of Medical Students and Residents: What Can Be Done to Build Trust," by Quinn Bott (Duration 4:09)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Uniformed Services University of Health Services, Bethesda, Maryland (Q.B.)Current Author Address: Quinn Bott; e-mail, quinn.[email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: SS1 ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
Two-step full-thickness resection with anchor device of a laterally spreading tumor inside a rectal recess in a patient with an ileorectal anastomosis
Authors: Benedetto Mangiavillano, Francesco Auriemma, Mario Bianchetti, Alessandro Repici
Journal: Endoscopy (2020)

For a recurrent adenoma or adenocarcinoma that has arisen on an anastomotic suture, surgical management with “re-do” anastomosis is usually considered the standard treatment. The reasons for this are the high risk of recurrence or incomplete excision after endoscopic mucosal resection (EMR) and the extreme difficulty of endoscopic submucosal dissection (ESD) owing to scar tissue. Few data have been published in the literature about the use of full-thickness resection device (FTRD)-assisted treatment of perianastomotic laterally spreading tumors.
Annals Story Slam - Innovations: Practices That Build Trust - Colleges Advisory Program
Authors: Robert Shochet
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 February 2020Annals Story Slam - Innovations: Practices That Build Trust - Colleges Advisory ProgramFREERobert Shochet, MDRobert Shochet, MDJohns Hopkins School of Medicine, Baltimore, Maryland (R.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W20-0006 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Innovations: Practices That Build Trust - Colleges Advisory Program "Innovations: Practices That Build Trust - Colleges Advisory Program," by Robert Shochet, MD (Duration 4:45)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Johns Hopkins School of Medicine, Baltimore, Maryland (R.S.)Current Author Address: Robert Shochet, MD; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: SS1 ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
Jerry Kirk: surgery professor, author, and widely respected figure in surgical education
Authors: Penny Warren
Journal: BMJ (2020)

kirk120220.f1 



For generations of trainee surgeons, buying a copy of Jerry Kirk’s Basic Surgical Techniques or General Surgical Operations was a rite of passage.

Kirk was a professor of surgery at the Royal Free Hospital in London, and, as a colleague said, “surgical education was his being.” He was a shrewd and generous mentor, believing it a privilege to pass on his skills and encourage trainees, whether in person or through his prose.

A very precise surgeon with high standards, he had learnt from greats such as Ian Aird and Norman Tanner, but was unhappy with the shortcomings of operative textbooks that he said did not tackle the hazards and difficulties of surgical procedures. He started writing practical “how-to” titles for trainee surgeons, beginning with A Manual of Abdominal Operations , which was published in 1967. His bestselling Basic Surgical Techniques followed in 1973 and General Surgical Operations in 1978.

Kirk wrote and edited texts into his 90s. He was a hard worker, always at his computer, …
Abstract 14566: Impact of Silent Myocardial Ischemia on One Year Mortality After Successful Coronary Intervention: Data From Japanese Multicenter (KICS) Registry
Authors: Kota Motozato, Kenji Sakamoto, Takayoshi Yamashita, Suguru Nagamatsu, Ryota Sato, Seiji Hokimoto, Shuichi Oshima, Koich Nakao, Kazuteru Fuijimoto, Yuji Miyao, Hideki Shimomura, Ryusuke Tsunoda, Hideki Maruyama, Toyoki Hirose, Daisuke Sueta, Satoshi Araki, Yuichiro Arima, Sunao Nakamura, Koichi Kaikita, Kenichi Tsujita
Journal: Circulation (2018)

Introduction: Under the awareness of appropriate use criteria, the significance of PCI for the patients with silent myocardial ischemia (SMI) decreases. On the other hand, the prognoses of SMI pati...
Abstract 16506: 1-Year Outcomes in Patients With Interstitial Lung Disease Undergoing Transcatheter versus Surgical Aortic Valve Replacement
Authors: Sameer Hirji, Jiyae Lee, Jennifer Choi, Siobhan McGurk, Marc Pelletier, Sary Aranki, Prem Shekar, Natalia Berry, Piotr Sobieszczyk, Pinak Shah, Tsuyoshi Kaneko
Journal: Circulation (2018)

Introduction: Patients with underlying interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF), represent a high-risk cohort given their increasing vulnerability for postoper...
Management of acute ischemic stroke
Authors: Michael S Phipps, Carolyn A Cronin
Journal: BMJ (2020)

ABSTRACT Stroke is the leading cause of long term disability in developed countries and one of the top causes of mortality worldwide. The past decade has seen substantial advances in the diagnostic and treatment options available to minimize the impact of acute ischemic stroke. The key first step in stroke care is early identification of patients with stroke and triage to centers capable of delivering the appropriate treatment, as fast as possible. Here, we review the data supporting pre-hospital and emergency stroke care, including use of emergency medical services protocols for identification of patients with stroke, intravenous thrombolysis in acute ischemic stroke including updates to recommended patient eligibility criteria and treatment time windows, and advanced imaging techniques with automated interpretation to identify patients with large areas of brain at risk but without large completed infarcts who are likely to benefit from endovascular thrombectomy in extended time windows from symptom onset. We also review protocols for management of patient physiologic parameters to minimize infarct volumes and recent updates in secondary prevention recommendations including short term use of dual antiplatelet therapy to prevent recurrent stroke in the high risk period immediately after stroke. Finally, we discuss emerging therapies and questions for future research.
MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming
Authors: Yang Liu, Li-Li Lu, Duo Wen, Dong-Li Liu, Li-Li Dong, Dong-Mei Gao, Xin-Yu Bian, Jian Zhou, Jia Fan, Wei-Zhong Wu
Journal: Journal of Hematology & Oncology (2020)

Abstract Background MicroRNA-612 (miR-612) has been proven to suppress EMT, stemness, and tumor metastasis of hepatocellular carcinoma (HCC) via PI3K/AKT2 and Sp1/Nanog signaling. However, its biological roles on HCC progression are far from elucidated. Methods We found direct downstream target of miR-612, hadha by RNA immunoprecipitation and sequencing. To explore its biological characteristic, potential molecular mechanism, and clinical relevance in HCC patients, we performed several in-vitro and in-vivo models, as well as human tissue chip. Results Ectopic expression of miR-612 could partially reverse the level of HADHA, then suppress function of pseudopods, and diminish metastatic and invasive potential of HCC by lipid reprogramming. In detail, miR-612 might reduce invadopodia formation via HADHA-mediated cell membrane cholesterol alteration and accompanied with the inhibition of Wnt/β-catenin regulated EMT occurrence. Our results showed that the maximum oxygen consumption rates (OCR) of HCCLM3 miR-612-OE and HCCLM3 hadha -KD cells were decreased nearly by 40% and 60% of their counterparts ( p &lt; 0.05). The levels of acetyl CoA were significantly decreased, about 1/3 ( p &gt; 0.05) or 1/2 ( p &lt; 0.05) of their controls, in exogenous miR-612 or hadha -shRNA transfected HCCLM3 cell lines. Besides, overexpression of hadha cell lines had a high expression level of total cholesterol, especially 27-hydroxycholesterol ( p &lt; 0.005). SREBP2 protein expression level as well as its downstream targets, HMGCS1, HMGCR, MVD, SQLE were all deregulated by HADHA. Meanwhile, the ATP levels were reduced to 1/2 and 1/4 in HCCLM3 miR-612-OE ( p &lt; 0.05) and HCCLM3 hadha -KD ( p &lt; 0.01) respectively. Moreover, patients with low miR-612 levels and high HADHA levels had a poor prognosis with shorter overall survival. Conclusion miR-612 can suppress the formation of invadopodia, EMT, and HCC metastasis and by HADHA-mediated lipid programming, which may provide a new insight of miR-612 on tumor metastasis and progression.
Vasoreactivity Test to Evaluate the Pulmonary Vascular Resistance and Mean Pulmonary Arterial Pressure by Doppler Echocardiography
Authors: Tania T. Muñoz H
Journal: Clinical Cardiology and Cardiovascular Interventions (2019)

The pulmonary vascular reactivity test (PVRT) is essential to define patients with pulmonary hypertension(PH) responders to calcium antagonist treatment, this is possible evaluating the changes registered in the 3 hemodynamic variables: pulmonary vascular resistance (PVR), mean pulmonary arterial pressure(MPAP) and cardiac output(CO).Cardiac catheterization is unquestionably the gold standard for performing the test, but its application implies high costs, technical boarding limitations, risks and complications minor to serious inherent to the procedure.On the other hand, Doppler echocardiography is harmless and economical, offering in the last 15 years a considerable advance in techniques and practical methods for estimating these variables, being the most analyzed and documented to date, the PVR.In this study we will review the different echocardiographic equations proposed by different authors to calculate the PVR and MPAP, in all cases, comparing the results obtained with the measurements made by the right heart catheterization (RHC) .The results obtained in them will be briefly mentioned and will give an important reference to the reader of a study done in our research center, where we grant a new use to the non-invasive measurement of MPAP applied in the PVRT.