tbuckley/cabot-search huggingface dataset:
Oncological Outcomes After Okabayashi-Kobayashi Radical Hysterectomy for Early and Locally Advanced Cervical Cancer
Authors: Noriaki Sakuragi, Tatsuya Kato, Chisa Shimada, Masanori Kaneuchi, Yukiharu Todo, Takashi Mitamura, Mahito Takeda, Masataka Kudo, Gen Murakami, Hidemichi Watari
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The role of surgery in early-stage cervical cancer has been established, but it is controversial in locally advanced cervical cancer. <h3>Objective</h3> To determine whether a radical hysterectomy method with extended removal of paracervical tissue for locally advanced cervical cancer is associated with satisfactory oncological outcomes. <h3>Design, Setting, and Participants</h3> This retrospective cohort study was conducted from January 1, 2002, to December 31, 2011, and participants were patients with cervical cancer at a single tertiary center in Northern Japan. The median follow-up period was 106 months, and none of the patients were lost to follow-up at less than 60 months. Data analyses were performed from July 1, 2017, to December 31, 2018. <h3>Exposures</h3> Patients underwent radical hysterectomy using the Okabayashi-Kobayashi method. Bilateral nerve preservation was used for stage IB1/IB2 disease and unilateral nerve preservation for stage IIA/IIB if disease extension outside the uterine cervix was 1-sided. Chemotherapy was used as the choice of adjuvant treatment for patients with an intermediate or high risk of recurrence, while some patients chose or were assigned to radiotherapy. <h3>Main Outcomes and Measures</h3> Primary outcomes were the 5-year local control rate and 5-year overall survival rate along with risk factor analysis. <h3>Results</h3> Of 121 consecutive patients, 76 (62.8%) had early-stage cervical cancer in 2008 International Federation of Gynecology and Obstetrics stages IB1 and IIA1 and 45 (37.2%) had locally advanced cervical cancer in stages IB2, IIA2, and IIB. The median (range) age was 42 (26-68) years. Adjuvant radiotherapy was used in 2 patients (3%) with early-stage cervical cancer and 3 (7%) of those with locally advanced cervical cancer. The 5-year local control rates for early-stage cervical cancer and locally advanced cervical cancer were 99% and 87%, respectively. The 5-year overall survival rates for early-stage cervical cancer and locally advanced cervical cancer were 95% and 82%, respectively. Cox regression analysis showed that lymph node metastasis and histology of adeno(squamous)carcinoma were independent risk factors for the overall survival of patients with cervical cancer treated with radical hysterectomy. <h3>Conclusions and Relevance</h3> The nerve-sparing Okabayashi-Kobayashi radical hysterectomy for locally advanced cervical cancer may provide survival not inferior to radical hysterectomy or radiotherapy in published literature. The applicability of radical hysterectomy with adjuvant chemotherapy for locally advanced cervical cancer needs to be validated by prospective comparative trials.
Congenital central hypoventilation syndrome. In: ATS Patient Series [updated March 2018 (from Am J Respir Crit Care Med 182:4-5, 2010) to partner with 2010 ATS Statement on CCHS].
Authors: DE Weese-Mayer, CM Rand, A Zhou, M Sockrider
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Some Effects of Digoxin on the Heart and Circulation in Man
Authors: RÉJANE M. HARVEY, M. IRENÉ FERRER, RICHARD T. CATHCART, JAMES K. ALEXANDER
Journal: Circulation (1951)

The early effect of intravenous Digoxin was observed in 12 patients with cardiac enlargement in whom there was no clinical or physiologic evidence of failure. There was either a fall or no change in the cardiac output and the intracardiac pressures did not alter following administration of the drug. The reaction to Digoxin in this type of patient with heart disease was in no way different from the response seen in two normal subjects included in the study but is in sharp contrast to the response elicited in patients in congestive heart failure.
Differences in 18F-FDG Uptake and Expression of Glucose Transporter Between 2 Distinct Subtypes of Mass-Forming Intrahepatic Cholangiocarcinomas
Authors: Kazuto Kozaka, Satoshi Kobayashi, Hiroyuki Takamura, Yasunori Sato, Azusa Kitao, Dai Inoue, Norihide Yoneda, Hidehiro Tajima, Seigo Kinuya, Kenichi Harada, Tetsuo Ohta, Wataru Koda, Osamu Matsui, Toshifumi Gabata
Journal: Clinical Nuclear Medicine (2020)

Recently, intrahepatic cholangiocarcinoma (iCCA) has been classified into small duct cholangiocarcinoma (SDC) and large duct cholangiocarcinoma (LDC) according to the origin of the biliary tree. Although the usefulness of F-FDG PET/CT in iCCA is well known, there are no reports evaluating differences in accumulation of F-FDG according to the recently described iCCA subtypes. The aim of this study was therefore to assess F-FDG accumulation and the expression of glucose transporters in SDC and LDC.Our institutional review board approved this retrospective study and waived the requirement for informed consent. Fourteen consecutive surgically resected mass-forming iCCA (7 SDCs, 23 ± 6.7 mm; 7 LDCs, 44 ± 26 mm) were enrolled. The SUVmax on F-FDG PET/CT and the expression of glucose transporter 1 (Glut-1), Glut-2, hexokinase 2 (HK2), and glucose-6-phosphatase by immunohistochemistry were evaluated and compared between SDC and LDC.The SUVmax in SDC was significantly lower than that in LDC (3.2 ± 0.8 vs 7.6 ± 3.2, P < 0.01). The staining scores of Glut-1 and HK2 were significantly lower in SDC than in LDC (0 vs 3 ± 1.4, P = 0.0034; 1.6 ± 1.1 vs 3.4 ± 1.1, P = 0.014, respectively). Expression levels of Glut-2 and glucose-6-phosphatase were variable and did not show a significant difference between SDC and LDC. Overall survival was significantly worse in LDC than in SDC (P = 0.01).F-FDG accumulation and Glut-1 and HK2 expression were significantly higher in LDC than in SDC. A low-glycolytic feature may be one of the characteristic findings of SDC.
COVID-19 Digestive System Involvement and Clinical Outcomes in a Large Academic Hospital in Milan, Italy
Authors: Alessio Aghemo, Daniele Piovani, Tommaso Lorenzo Parigi, Enrico Brunetta, Nicola Pugliese, Edoardo Vespa, Paolo Dario Omodei, Paoletta Preatoni, Ana Lleo, Alessandro Repici, Antonio Voza, Maurizio Cecconi, Alberto Malesci, Stefanos Bonovas, Silvio Danese
Journal: Clinical Gastroenterology and Hepatology (2020)

Since February 2020, the COVID-19 pandemic has spread to Italy affecting more than 100,000 people. Several studies have reported a high prevalence of gastrointestinal (GI) symptoms, and investigated their potential association with clinical outcomes.1 The timing, clinical significance, and possible impact on viral spread of GI symptoms presentation have not been fully elucidated. Elevation of liver function tests and other laboratory values has also been reported; however, their prognostic significance has not been clearly established.2.
33 LIVER TRANSPLANTATION FOR ERYTHROPOIETIC PROTOPORPHYRIA IN EUROPE
Authors: S. Wahlin, P. Stål, R. Adam, V. Karam, P. Porte, D. Seehofer, B.K. Gunson, J. Hillingsø, J.L. Klempnauer, J. Schmidt, G. Alexander, J. O'Grady, P.A. Clavien, M. Salizzoni, A. Paul, K. Rolles, B.G. Ericzon, P. Harper
Journal: Journal of Hepatology (2011)
Investigation of the role and mechanism of ARHGAP5-mediated colorectal cancer metastasis
Authors: Tian Tian, Zhan-Hong Chen, Zongheng Zheng, Yubo Liu, Qi Zhao, Yuying Liu, Huijun Qiu, Qian Long, Miao Chen, Liren Li, Fangyun Xie, Guangyu Luo, Xiaojun Wu, Wuguo Deng
Journal: Theranostics (2020)

Background: Metastatic colorectal cancer (CRC) is a lethal disease; however, the underlying molecular mechanisms remain unclear and require further study. Methods: RNA-Seq, PCR, Western blotting, immunohistochemistry, ChIP and RNAi assays were performed to investigate Rho GTPase-activating protein 5 (ARHGAP5, aslo known as p190RhoGAP-B, p190-B) expression and the clinical relevance, functional roles and regulatory mechanisms of this protein using human CRC cells and tissues. In vivo, two cell-based xenograft models were used to evaluate the roles of ARHGAP5 in CRC metastasis. Results: Here, we report that ARHGAP5 expression is significantly increased in metastatic CRC tissues and is inversely associated with patient overall survival. The suppression of ARHGAP5 reduces CRC cell metastasis in vitro and in cell-based xenograft models. Furthermore, we show that ARHGAP5 promotes CRC cell epithelial-mesenchymal transition by negatively regulating RhoA activity. Mechanistically, cAMP response element-binding protein (CREB1) transcriptionally upregulates ARHGAP5 expression, and decreased miR-137 further contributes to ARHGAP5 mRNA stability in CRC. Conclusions: Overall, our study highlights the crucial function of ARHGAP5 in CRC metastasis, thus suggesting novel prognostic biomarkers and hypothetical therapeutic targets.
A Randomized Trial of Icatibant in ACE-Inhibitor–Induced Angioedema
Authors: Ulrich Strassen, Jens Greve, Klaus Stelter, Miriam Havel, Nicole Rotter, Johannes Veit, Beate Schossow, Alexander Hapfelmeier, Victoria Kehl, Georg Kojda, Thomas K. Hoffmann, Murat Bas
Journal: Journal of Allergy and Clinical Immunology (2016)
Связь биомаркеров воспаления в толстой кишке с индексами активности неспецифического язвенного колита
Authors: I.V. Psareva
Journal: GASTROENTEROLOGY (2020)

Цель: проанализировать содержание маркеров кишечного воспаления в крови и кале больных с неспецифическим язвенным колитом (НЯК) в сопоставлении с известными индексами активности болезни. Материалы и методы. Исследованы 60 пациентов с подтвержденным диагнозом НЯК. Клиническую активность НЯК оценивали с помощью клинического индекса активности по D. Rachmilewitz. Эндоскопическая активность НЯК определялась по индексу Mayo. Степень активности НЯК оценивали по комбинированному индексу Mayo. В сыворотке крови определяли содержание α-1-антитрипсина и С-реактивного белка. В кале исследовали содержание миелопероксидазы, кальпротектина и α-1-антитрипсина. Корреляционный анализ осуществляли с расчетом коэффициента корреляции Спирмена и его значимости. Результаты. У больных НЯК выявлено существенное повышение уровня фекальной миелопероксидазы в 4,5 раза (р = 0,027) и α-1-антитрипсина в кале в 3,6 раза (р = 0,039) по мере увеличения клинической активности НЯК. При выраженной степени эндоскопической активности НЯК отмечено достоверное увеличение уровня маркеров воспаления в кале: α-1-антитрипсина — в 17,8 раза (р = 0,037), кальпротектина — в 1,7 раза (р = 0,023), миелопероксидазы — 4,3 раза (р = 0,019). В то же время уровни С-реактивного белка и α-1-антитрипсина в крови не имели значимых различий в зависимости от степени активности НЯК. Выводы. У пациентов с НЯК установлены взаимосвязи уровня миелопероксидазы и кальпротектина в кале с индексом эндоскопической активности (r = 0,63, p = 0,0008 и r = 0,53, p = 0,001 соответственно), а также уровня фекальной миелопероксидазы со степенью активности заболевания согласно комбинированному индексу Mayo (r = 0,68, p = 0,0001).
Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists
Authors: Maximilian F. Konig, Mike Powell, Verena Staedtke, Ren-Yuan Bai, David L. Thomas, Nicole Fischer, Sakibul Huq, Adham M. Khalafallah, Allison Koenecke, Ruoxuan Xiong, Brett Mensh, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Joshua T. Vogelstein, Susan Athey, Shibin Zhou, Chetan Bettegowda
Journal: Journal of Clinical Investigation (2020)

Dysregulated host immune responses drive mortality in pneumonia and acute respiratory distress syndrome (ARDS) caused by a wide range of infections.In coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicits an exuberant local or systemic immune response (hyperinflammation) in the lung and other sites of viral replication, compromising organ function and leading to high morbidity and mortality (1-4).
Abstract A40: Protein disulfide isomerases in the endoplasmic reticulum promote anchorage-independent growth of breast cancer cells
Authors: Randi Wise, Sara Duhachek-Muggy, Yue Qi, Michal Zolkiewski, Anna Zolkiewska
Journal: Cancer Research (2016)

Abstract Cancer cells that separate from primary tumors and migrate to metastatic sites are exposed to stress caused by detachment from the extracellular matrix (ECM). Cultured breast cancer cells that survive this stress and are capable of anchorage-independent proliferation form mammospheres. Biological mechanisms responsible for maintaining the mammosphere-growth competence are not fully understood. We hypothesized that mammosphere growth requires elevated ECM secretion, which demands efficient folding quality control in the endoplasmic reticulum (ER). We found that SUM159PT and MCF10DCIS.com breast cancer cells grown as mammospheres had elevated mRNA and protein levels of three protein disulfide isomerases: ERp57, ERp44, and PDI. We also found an increased phosphorylation of eIF2alpha in mammospheres, suggesting that the PERK arm of the unfolded protein response was activated. An inducible knock-down of ERp57 in SUM159PT cells resulted in impaired ability to form mammospheres. Analysis of a publicly available gene expression data for circulating tumor cells (CTCs) revealed that up-regulation of ECM genes and ER folding quality control genes occurred at the time of disease progression and surge in the number of CTCs. These data indicate that breast cancer cell survival and growth under detachment conditions require enhanced assistance of the ER folding machinery in the correct disulfide bond formation. Citation Format: Randi Wise, Sara Duhachek-Muggy, Yue Qi, Michal Zolkiewski, Anna Zolkiewska. Protein disulfide isomerases in the endoplasmic reticulum promote anchorage-independent growth of breast cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A40.
ATOPAXAR AND ITS EFFECTS ON MARKERS OF PLATELET ACTIVATION AND INFLAMMATION: RESULTS FROM THE LANCELOT PROGRAM
Authors: Michelle L. O&apos;Donoghue, Deepak Bhatt, Marcus Flather, Shinya Goto, Dominick Angiolillo, Shaun Goodman, Uwe Zeymer, Philip Aylward, Gilles Montalescot, Rafal Ziecina, Fang Ren, Stephen Wiviott
Journal: Journal of the American College of Cardiology (2012)
1425 SIMEPREVIR (TMC435) WITH PEGINTERFERON/RIBAVIRIN FOR CHRONIC HCV GENOTYPE-1 INFECTION IN TREATMENT-NAÏVE PATIENTS: RESULTS FROM QUEST-1, A PHASE III TRIAL
Authors: I. Jacobson, G.J. Dore, G.R. Foster, M.W. Fried, M. Radu, V.V. Rafalskiy, L. Moroz, A. Craxi, M. Peeters, O. Lenz, S. Ouwerkerk-Mahadevan, R. Kalmeijer, M. Beumont-Mauviel
Journal: Journal of Hepatology (2013)
Abstract 4498: CKD-516 displays vascular disrupting properties and enhances anti-tumor activity in combination with chemotherapy in a murine tumor model.
Authors: Young Joo Min, Chang Hoon Moon, Seung Ju Lee, Sang Ryun Ryu, Wha Ja Cho, Nal Ae Yoon, Sungchan Park, HeeJeong Cha
Journal: Cancer Research (2013)

Abstract PURPOSE: CKD-516 is a benzophenone analog with a modification of the B ring, which is replaced by a carbonyl group. The aim of this study is to assess the antivascular effects and the inhibition of cell proliferation of CKD-516. MATERIALS AND METHODS: To assess the effect of CKD-516 on vascularization, we analyzed the effect on endothelial cells (HUVECs). To determine the inhibition of cell proliferation of CKD-516, we used a lung carcinoma cell line (H460). The alteration of microtubule analyzed using immunoblot, RT-PCR and confocal image. To evaluate the anti-tumor effects of gemcitabine and/or CKD-516, H460 xenograft mice were treated with CKD-516 (2.5 mg/kg) or gemcitabine (40 mg/kg) or CKD-516 + gemcitabine, and tumor growth was compared with vehicle-treated control. For histologic analysis, liver, spleen and tumor tissues were taken at 12 and 24 hours after CKD-516 injection from H460 xenograft mice. RESULTS: We determined that cytoskeletal changes of HUVECs treated with 10 nM CKD-516 were assessed by immunoblot and confocal imaging. CKD-516 disrupts tubulin assembly and results in microtubule dysfunction inducing cell cycle arrest (G2/M). CKD-516 markedly enhanced the depolymerization of microtubules which may be related to vascular disrupting properties of CKD-516. Interestingly, CKD-516 decreased amount of total tubulin protein in HUVECs. Especially, CKD-516 decreased mRNA expression α-tubulin (HUVECs only) and β-tubulin (HUVECs and H460) at early time point (4 h). Immunocytochemical analysis showed that CKD-516 changed the cellular microtubule network and inhibited the formation of polymerized microtubules. We also showed extensive central necrosis of tumor by 24 h after treated with CKD-516 (2.5 mg/kg, i.p.). In H460 xenograft, CKD-516 combined with gemcitabine significantly delayed tumor growth as compared to control and gemcitabine alone. CONCLUSION: These results suggest that CKD-516 is a novel agent with vascular disrupting properties, and enhances anti-tumor activity in combination with chemotherapy. Citation Format: Young Joo Min, Chang Hoon Moon, Seung Ju Lee, Sang Ryun Ryu, Wha Ja Cho, Nal Ae Yoon, Sungchan Park, HeeJeong Cha. CKD-516 displays vascular disrupting properties and enhances anti-tumor activity in combination with chemotherapy in a murine tumor model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4498. doi:10.1158/1538-7445.AM2013-4498
Five-year Outcomes of Magnetic Resonance Imaging–based Active Surveillance for Prostate Cancer: A Large Cohort Study
Authors: Vasilis Stavrinides, Francesco Giganti, Bruce Trock, Shonit Punwani, Clare Allen, Alex Kirkham, Alex Freeman, Aiman Haider, Rhys Ball, Neil McCartan, Hayley Whitaker, Clement Orczyk, Mark Emberton, Caroline M. Moore
Journal: European Urology (2020)

Although the use of multiparametric magnetic resonance imaging (mpMRI) in active surveillance (AS) for prostate cancer is of increasing interest, existing data are derived from small cohorts.We describe clinical, histological, and radiological outcomes from an established AS programme, where protocol-based biopsies were omitted in favour of MRI-led monitoring.Data on 672 men enrolled in AS between August 2004 and November 2017 (inclusion criteria: Gleason 3 + 3 or 3 + 4 localised prostate cancer, presenting prostate-specific antigen <20 ng/ml, and baseline mpMRI) were collected from the University College London Hospital (UCLH) database.Primary outcomes were event-free survival (EFS; event defined as prostate cancer treatment, transition to watchful waiting, or death) and treatment-free survival (TFS). Secondary outcomes included rates of all-cause or prostate cancer-related mortality, metastasis, and upgrading to Gleason ≥4 + 3. Data on radiological and histological progression were also collected.More than 3800 person-years (py) of follow-up were accrued (median: 58 mo; interquartile range 37-82 mo). Approximately 84.7% (95% confidence interval [CI]: 82.0-87.6) and 71.8% (95% CI: 68.2-75.6) of patients remained on AS at 3 and 5 yr, respectively. EFS and TFS were lower in those with MRI-visible (Likert 4-5) disease or secondary Gleason pattern 4 at baseline (log-rank test; p < 0.001). In total, 216 men were treated. There were 24 deaths, none of which was prostate cancer related (6.3/1000 py; 95% CI: 4.1-9.5). Metastases developed in eight men (2.1 events/1000 py; 95% CI: 1.0-4.3), whereas 27 men upgraded to Gleason ≥4 + 3 on follow-up biopsy (7.7 events/1000 py; 95% CI: 5.2-11.3).The rates of discontinuation, mortality, and metastasis in MRI-led surveillance are comparable with those of standard AS. MRI-visible disease and/or secondary Gleason grade 4 at baseline are associated with a greater likelihood of moving to active treatment at 5 yr. Further research will concentrate on optimising imaging intervals according to baseline risk.In this report, we looked at the outcomes of magnetic resonance imaging (MRI)-based surveillance for prostate cancer in a UK cohort. We found that this strategy could allow routine biopsies to be avoided. Secondary Gleason pattern 4 and MRI visibility are associated with increased rates of treatment. We conclude that MRI-based surveillance should be considered for the monitoring of small prostate tumours.
Manson's Tropical Diseases.
Journal: Annals of Internal Medicine (1973)

This book continues to be one of the most outstanding in the world on the subject of tropical disease. It is a complete single volume concerned with tropical medicine, but, like all single volumes, it is not truly encyclopedic. This thirteenth edition has been brought up to date to include the new antibiotic drugs and the experiences obtained during World War II. This book is highly recommended to students of tropical medicine, especially those interested in the British points of view.
COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain
Authors: Marian Goicoechea, Luis Alberto Sánchez Cámara, Nicolás Macías, Alejandra Muñoz de Morales, Ángela González Rojas, Arturo Bascuñana, David Arroyo, Almudena Vega, Soraya Abad, Eduardo Verde, Ana María García Prieto, Úrsula Verdalles, Diego Barbieri, Andrés Felipe Delgado, Javier Carbayo, Antonia Mijaylova, Adriana Acosta, Rosa Melero, Alberto Tejedor, Patrocinio Rodriguez Benitez, Ana Pérez de José, María Luisa Rodriguez Ferrero, Fernando Anaya, Manuel Rengel, Daniel Barraca, José Luño, Inés Aragoncillo
Journal: Kidney International (2020)
Abstract P399: Cardiovascular and Non-Cardiovascular Disease Associations with Hip Fractures in the Elderly: A Population-Based Case-Control Study
Authors: Yariv Gerber, L. J Melton, Sheila M McNallan, Ruoxiang Jiang, Susan A Weston, Veronique L Roger
Journal: Circulation (2012)

Background: There is growing awareness of an association between cardiovascular disease (CVD) and fractures, and a temporal increase in fracture risk after myocardial infarction has been noted but the mechanisms are not delineated. To evaluate this relationship, we systematically examined the association of hip fracture with all disease categories and assessed related secular trends. Methods: Using resources of the Rochester Epidemiology Project, a population-based incident case-control study was conducted. Disease history was compared between all Olmsted County, Minnesota, residents aged 50 years or older with a first hip fracture in 1985–2006 and community control subjects individually matched (1:1) to cases on age, sex, and index year (n=3,808; mean age [SD], 82 [9] years; 76% women). Results: All CVD and numerous non-CVD categories (e.g., infectious diseases, nutritional and metabolic diseases, mental disorders, diseases of the nervous system and sense organs, and diseases of the respiratory system) were associated with fracture risk. However, increasing temporal trends were almost exclusively detected in categories of CVD (Figure). The largest increases in association were observed for ischemic heart disease, other forms of heart disease (including heart failure), hypertension, and diabetes and were more pronounced among elderly women than other demographic groups. Conclusions: While the association with hip fracture was not specific to CVD, temporal increases were mainly detected in cardio-metabolic diseases, all of which have also been linked previously to frailty. This could delineate a common pathway that warrants further investigation.