tbuckley/cabot-search huggingface dataset:
Хронічний гастрит: континуум діагностики й лікування
Authors: Yu.M. Stepanov, I.V. Kushnirenko
Journal: GASTROENTEROLOGY (2020)

У статті викладені основні етапи розвитку поглядів на діагностику хронічного гастриту з висвітленням проблеми діагностики як невід’ємної частини комплексу заходів щодо своєчасного виявлення пренеопластичних змін слизової оболонки шлунка. Подані основні погляди на шляхи розвитку канцерогенезу з урахуванням сучасних знань про фактори, що впливають на перебіг цього процесу. Серед відомих заходів щодо запобігання розвитку преканцерозних змін на сьогодні найбільш важливими є надійна стратифікація груп ризику їх розвитку та стратегія виявлення й усунення Helicobacter pylori як визнаного фактора канцерогенезу. Розвиток резистентності бактерії до базових препаратів, рекомендованих для включення у схеми ерадикаційної терапії, зумовлює подальший пошук способів підвищення їх ефективності. Як показано в низці досліджень, результати яких наведені в статті, найбільш надійним є додавання до схем ерадикації субцитрату вісмуту (Де-Нол).
Residual risk of breast cancer recurrence 5 years after adjuvant therapy
Authors: Abenaa Brewster, Gabriel Hortobagyi, Kristine Broglio, Shu-Wan Kau, Cesar Santa-Maria, Banu Arun, Aman Buzdar, Daniel Booser, Vincente Valero, Francisco Esteva
Journal: Cancer Research (2008)

3892    Background:  A substantial number of patients remain at risk for late breast cancer recurrences after initial adjuvant systemic therapy (AST). Identifying patients who have a high residual risk of recurrence has important clinical relevance since extended AST therapy with aromatase inhibitors improves disease-free survival in estrogen receptor (ER) or progesterone receptor (PR) breast cancers. We evaluated the magnitude of the residual risk of recurrence among early stage breast cancer patients who remained alive and disease-free 5 years after starting AST and examined the effect of clinical factors on their 5-year residual recurrence-free survival.  Methods:  Patients (n=2,840) treated at the MD Anderson Cancer Center between 1985 and 2001 for stages I-III breast cancer and who remained alive and disease-free 5 years after the start of AST were identified from our patient databases. The Kaplan-Meier product limit method was used to estimate the recurrence-free survival and the log-rank test was used to compare groups. All statistical tests were two sided and  P  values less than 0.05 were considered statistically significant.  Results:  The majority of patients (52%) were postmenopausal and 9% were Black, 12% Hispanic and 73% White. The median follow-up time for all patients calculated from the 5 year disease-free anniversary to breast cancer recurrence was 28 months. The median time to breast cancer recurrence calculated from the 5 year disease-free anniversary to breast cancer recurrence was not reached. The 5-year residual risk of recurrence was 7% in stage I, 12% in stage II and 13% in stage III patients. In multivariate analysis, stage II or III disease, nuclear grade 1 tumors (well differentiated) and ER or PR positive tumors were statistically significantly associated with an increased residual risk of recurrence.  Conclusion:  Breast cancer patients remain at substantially increased risk for recurrence 5 years after starting AST. The residual risk of recurrence was greater in patients with ER or PR positive disease versus ER and PR negative disease supporting the use of extended AST. A higher proportion of nuclear grade 1 breast cancers were ER or PR positive which may explain the increased residual risk of recurrence associated with these tumors. Further research is needed to identify host and tumor characteristics predictive of late recurrences in order to individualize both initial and extended AST.
Effectiveness of and overdiagnosis from mammography screening in the Netherlands: population based study
Authors: Philippe Autier, Magali Boniol, Alice Koechlin, Cécile Pizot, Mathieu Boniol
Journal: BMJ (2017)

<h3>Abstract</h3> <h3>Objective</h3> To analyse stage specific incidence of breast cancer in the Netherlands where women have been invited to biennial mammography screening since 1989 (ages 50-69) and 1997 (ages 70-75), and to assess changes in breast cancer mortality and quantified overdiagnosis. <h3>Design</h3> Population based study. <h3>Setting</h3> Mammography screening programme, the Netherlands. <h3>Participants</h3> Dutch women of all ages, 1989 to 2012. <h3>Main outcome measures</h3> Stage specific age adjusted incidence of breast cancer from 1989 to 2012. The extra numbers of in situ and stage 1 breast tumours associated with screening were estimated by comparing rates in women aged 50-74 with those in age groups not invited to screening. Overdiagnosis was estimated after subtraction of the lead time cancers. Breast cancer mortality reductions during 2010-12 and overdiagnosis during 2009-11 were computed without (scenario 1) and with (scenario 2) a cohort effect on mortality secular trends. <h3>Results</h3> The incidence of stage 2-4 breast cancers in women aged 50 or more was 168 per 100 000 in 1989 and 166 per 100 000 in 2012. Screening would be associated with a 5% mortality reduction in scenario 1 and with no influence on mortality in scenario 2. In both scenarios, improved treatments would be associated with 28% reductions in mortality. Overdiagnosis has steadily increased over time with the extension of screening to women aged 70-75 and with the introduction of digital mammography. After deduction of clinical lead time cancers, 32% of cancers found in women invited to screening in 2010-12 and 52% of screen detected cancers would be overdiagnosed. <h3>Conclusions</h3> The Dutch mammography screening programme seems to have little impact on the burden of advanced breast cancers, which suggests a marginal effect on breast cancer mortality. About half of screen detected breast cancers would represent overdiagnosis.
Safety and efficacy of guselkumab in Japanese patients with moderate-to-severe plaque psoriasis: a randomized, placebo-controlled, ascending-dose study
Authors: O. Nemoto, K. Hirose, S. Shibata, K. Li, H. Kubo
Journal: British Journal of Dermatology (2017)

The interleukin (IL)‐23/IL‐17 pathway is central in the pathogenesis of psoriasis. The favourable efficacy and safety of guselkumab, an IL‐23‐specific monoclonal antibody, has been demonstrated in global phase III studies of plaque psoriasis. To evaluate the safety, efficacy and pharmacokinetics of single‐dose subcutaneous guselkumab in Japanese patients with moderate‐to‐severe plaque psoriasis. Patients with ≥ 10% of total body surface area involvement and a Psoriasis Area and Severity Index (PASI) ≥ 12 were randomized (5 : 1) to receive guselkumab or placebo in four cohorts of this double‐blind, placebo‐controlled, single ascending‐dose, single‐centre study. Safety, pharmacokinetics and clinical response were monitored at baseline and specific time points over a 24‐week follow‐up period. To week 24, 55% (11/20) of patients in the guselkumab group and 50% (2/4) in the placebo group experienced ≥1 adverse event (AE). No deaths, serious AEs or AEs leading to treatment discontinuation were reported. Maximum clinical response was seen at week 16 with PASI 75 (≥ 75% improvement from baseline PASI) response in two of five (10 mg), four of five (30 mg and 300 mg) and three of five (100 mg) patients; and PASI 90 (≥ 90% improvement from baseline PASI) in zero of five (10 mg), three of five (30 mg), two of five (100 mg) and three of five (300 mg) patients. Mean maximum serum concentration (Cmax) and area under the curve from time zero to infinity values increased in a dose‐proportional manner with a mean terminal half‐life of 15·6–17·6 days and median time to reach Cmax of 4–6 days. Guselkumab was generally well‐tolerated and exhibited sustained high levels of clinical response in Japanese patients with moderate‐to‐severe psoriasis.
A Novel Technique to Measure the Intensity of Abnormality on GI Bleeding Scans
Authors: Rami Farhat, Derek T. Kim, T. Dustin French, Dov Bechhofer, Anca-Oana Kranz, Jason C. Hoffmann
Journal: Clinical Nuclear Medicine (2017)

Develop a technique to quantify intensity of lower gastrointestinal bleeding (LGIB) on Tc-labeled red blood cell (RBC) scintigraphy, correlate with angiography, and determine the tool's predictive value.An IRB-approved, single institution database query of GI bleeding scans performed between January 2013 and December 2015. Reports from all studies and imaging from all positive studies were reviewed. A technique was developed for scan analysis, allowing for calculation of percent increase of activity in the region of interest (ROI, area of bleeding) and ROI in the aorta and liver (controls). Database query determined which patients underwent angiography, and which had positive angiograms. Median ROI percent increase in patients with positive scintigraphy and positive angiography was compared to those with positive scintigraphy and negative angiography.Of 194 bleeding scans performed during the study period, 71 were positive for active LGIB, 37 had angiography, and 9 had active contrast extravasation. The new tool was used to analyze the 37 cases with positive nuclear scans sent for angiography. Median percent increase in ROI activity was 50% in those with positive scan and positive angiogram and 26.8% in those with positive scan but negative angiogram. Using ROI percent change quartiles, we observed a statistically significant association between percent increase in ROI activity from baseline and the probability of having a positive angiogram (Cochran-Armitage trend test, P = 0.01), such that there are no positive angiogram cases when ROI change was <20% and a majority of the positive angiogram cases (67%) in the highest quartile.Utilization of processing protocol to determine percent increase in activity from baseline within ROI of active LGIB on scintigraphy has predictive value in determining which patients will not benefit from conventional angiography.
Effect of Levothyroxine on Miscarriage Among Women With Normal Thyroid Function and Thyroid Autoimmunity Undergoing In Vitro Fertilization and Embryo Transfer
Authors: Haining Wang, Hongwei Gao, Hongbin Chi, Lin Zeng, Wenhua Xiao, Yanrong Wang, Rong Li, Ping Liu, Chen Wang, Qing Tian, Zehong Zhou, Jin Yang, Ye Liu, Rui Wei, Ben Willem J. Mol, Tianpei Hong, Jie Qiao
Journal: JAMA (2017)

<h3>Importance</h3> Presence of thyroid autoantibodies in women with normal thyroid function is associated with increased risk of miscarriage. Whether levothyroxine treatment improves pregnancy outcomes among women undergoing in vitro fertilization and embryo transfer (IVF-ET) is unknown. <h3>Objective</h3> To determine the effect of levothyroxine on miscarriage among women undergoing IVF-ET who had normal thyroid function and tested positive for thyroid autoantibodies. <h3>Design, Setting, and Participants</h3> An open-label, randomized clinical trial involving 600 women who tested positive for the antithyroperoxidase antibody and were being treated for infertility at Peking University Third Hospital from September 2012 to March 2017. <h3>Interventions</h3> The intervention group (n = 300) received either a 25-μg/d or 50-μg/d dose of levothyroxine at study initiation that was titrated according to the level of thyroid-stimulating hormone during pregnancy. The women in the control group (n = 300) did not receive levothyroxine. All participants received the same IVF-ET and follow-up protocols. <h3>Main Outcomes and Measures</h3> The primary outcome was the miscarriage rate (pregnancy loss before 28 weeks of gestation, which was calculated among women who became pregnant). The secondary outcomes were clinical intrauterine pregnancy rate (fetal cardiac activity seen at sonography observation on the 30th day after the embryo transfer), and live-birth rate (at least 1 live birth after 28 weeks of gestation). <h3>Results</h3> Among the 600 women (mean [SD] age, 31.6 [3.8] years) randomized in this trial, 567 women (94.5%) underwent IVF-ET and 565 (94.2%) completed the study. Miscarriage rates were 10.3% (11 of 107) in the intervention group and 10.6% (12 of 113) in the control group, with the absolute rate difference (RD) of −0.34% (95% CI, −8.65% to 8.12%) over the 4.5-year study period. Clinical intrauterine pregnancy rates were 35.7% (107 of 300) in the intervention group and 37.7% (113 of 300) in the control group, with an absolute RD of −2.00% (95% CI, −9.65% to 5.69%). Live-birth rates were 31.7% (95 of 300) in the intervention group and 32.3% (97 of 300) in the control group, with an absolute RD of −0.67% (95% CI, −8.09% to 6.77%). <h3>Conclusions and Relevance</h3> Among women in China who had intact thyroid function and tested positive for antithyroperoxidase antibodies and were undergoing IVF-ET, treatment with levothyroxine, compared with no levothyroxine treatment, did not reduce miscarriage rates or increase live-birth rates. <h3>Trial Registration</h3> Chinese Clinical Trial Registry:ChiCTR-TRC-13004097
Cardiac Fibroma
Authors: Sarah Pittman, Pooja Sethi, Robert R. Flavell, Miguel Hernandez Pampaloni
Journal: Clinical Nuclear Medicine (2017)

A 66-year-old woman was referred for evaluation of coronary artery disease. Myocardial perfusion imaging (MPI) was performed, and showed a medium-sized, severe fixed perfusion defect in the inferior and inferolateral wall from apex to midcavity. On review of prior imaging, it was noted that the patient had an incidental finding of an intramural cardiac mass on chest CT performed 8 years prior. Subsequent cardiac MRI showed findings consistent with a cardiac fibroma in the left ventricle, at the location of the perfusion defect on MPI. Our case demonstrates an uncommon cause of a fixed perfusion defect on MPI.
<i>Helicobacter pylori</i> eradication failure may have confounded the recent large-scale health database study that showed proton pump inhibitors increase gastric cancer risk
Authors: Hidekazu Suzuki, Juntaro Matsuzaki
Journal: Gut (2017)

The current guidelines recommend that when patients require long-term use of proton pump inhibitors (PPIs), Helicobacter pylori  ( H. pylori ) should be eradicated beforehand because it improves atrophic gastritis, a precancerous lesion.1 2 The recent analysis by Cheung et al 3 of the data of more than 60 000 adults registered in a territory-wide health database in Hong Kong who underwent H. pylori eradication showed that the long-term use of PPIs increased the risk of gastric cancer by 2.4-fold. Moreover, the risk of gastric cancer increased with the dose and duration of PPI use. The fact that long-term PPI administration increases the risk of gastric cancer even after H. pylori eradication is unexpected. …
Disclosures in Nutrition Research
Authors: John P. A. Ioannidis, John F. Trepanowski
Journal: JAMA (2017)

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Irisin protects mitochondria function during pulmonary ischemia/reperfusion injury
Authors: Ken Chen, Zaicheng Xu, Yukai Liu, Zhen Wang, Yu Li, Xuefei Xu, Caiyu Chen, Tianyang Xia, Qiao Liao, Yonggang Yao, Cindy Zeng, Duofen He, Yongjian Yang, Tao Tan, Jianxun Yi, Jingsong Zhou, Hua Zhu, Jianjie Ma, Chunyu Zeng
Journal: Science Translational Medicine (2017)

Irisin protects against ischemia/reperfusion injury to the lung by improving mitochondrial function.
Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism
Authors: Gary E. Raskob, Nick van Es, Peter Verhamme, Marc Carrier, Marcello Di Nisio, David Garcia, Michael A. Grosso, Ajay K. Kakkar, Michael J. Kovacs, Michele F. Mercuri, Guy Meyer, Annelise Segers, Minggao Shi, Tzu-Fei Wang, Erik Yeo, George Zhang, Jeffrey I. Zwicker, Jeffrey I. Weitz, Harry R. Büller
Journal: New England Journal of Medicine (2017)

Low-molecular-weight heparin is the standard treatment for cancer-associated venous thromboembolism. The role of treatment with direct oral anticoagulant agents is unclear.
Abstract 228: HYQVIA in Postural Orthostatic Tachycardia Syndrome(POTS)
Authors: Muhammad M Ahsan, Tara Thompson, Chandralekha Ashangari, Amer Suleman
Journal: Circulation Research (2016)

Postural Orthostatic Tachycardia Syndrome (POTS) is a form of dysautonomia associated with variety of symptoms like Headache, Abdominal discomfort, Dizziness/presyncope, Nausea, Fatigue, Lightheadedness, Sweating Sleep disorder, Tremor, Anxiety, Palpitations, Exercise intolerance which is believed to be caused by an underlying infectious and/or autoimmune trigger. HYQVIA is an immune globulin with a recombinant human hyaluronidase indicated for the treatment of Primary Immunodeficiency (PI) in adults. This includes, but is not limited to, common variable immunodeficiency (CVID), X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies. HYQVIA is a gammaglobulin and is a slow metabolizer given subcutaneously once a month.There is data that Intravenous immunoglobulin(IVIg) helps POTS patients. We present a case of 57 year old female diagnosed with autonomic failure,orthostatic intolerance and primary immune deficiency. She was given IVIg for primary immune deficiency. She was previously reported for severe autonomic failure. From then, she was doing extremely well, had more energy and she thinks more clearly. She also had much better attitude. She was getting albumin every 2 weeks or so for volume expansion. She felt IVIg had helped her. Her immunoglobulin was switched from Gammagard to HYQVIA 35 grams. After she did, her blood pressure had gone up. She took it with albumin and she felt palpitations and chest pain.She was stopped on albumin, as albumin and HYQVIA combined could cause more volume expansion and push her into fluid overload or even congestive heart failure. After she stopped albumin without HYQVIA, she did well. Similarly, she cut back on midodrine which is an α1 adrenergic agonist, and works by stimulating receptors that noradrenaline normally works on. After swallowing, midodrine is rapidly converted into another, more active drug that binds to noradrenaline receptors causing blood vessels to narrow, thereby increasing blood pressure andreduction in heart rate in POTS patients. She was only HYQVIA and had been feeling extremely well.
Abstract IA22: Emerging signaling pathways in prostate cancer therapy
Authors: Luiz F. Zerbini
Journal: Cancer Research (2017)

Abstract One major prerequisite to develop targeted therapies is the identification of relevant cellular targets and the identification of the relevant patient population in which to test these therapies. Although androgen ablation therapy, surgery and radiation therapy are effective for the treatment of local prostate cancer (PCa), there is no effective treatment available for patients with metastatic disease. The receptor tyrosine kinase Axl has been implicated in the pathology of many cancers. Increased Axl expression correlates with metastasis, aggressive behavior, and poor survival and have been linked with resistance to chemotherapeutic regimens in tumors. Interestingly, in these reports inhibition of Axl leads to restoration of sensitivity to drug therapy, indicating that Axl may represent a promising therapeutic target whose inhibition could prevent or overcome acquired resistance to some drugs. We have shown that Axl is overexpressed in PCa and is an essential regulator of PCa proliferation and tumor growth. Axl expression is elevated in hormone-refractory PCa cell lines and Axl knockdown reduces migration and invasion and tumor formation in vivo. The Axl ligand, GAS6, acts as a growth and/or survival factor and its binding to Axl activates PI3K and its downstream targets S6K and Akt. Activation of these pathways has been reported to induce nuclear translocation of the transcription factor nuclear factor kappa B (NF-κB), IL-6 production and STAT3 activation. The molecule named R428 (now renamed BGB324) inhibits in a dose-dependent manner Gas6 stimulated Axl autophosphorylation and activity with high specificity, selectivity, and affinity and blocks Axl-dependent signaling events, such as Akt phosphorylation, cell invasion, and pro-inflammatory cytokine production. R428/BGB324 effectively prevents or reverses acquired resistance to several cancer therapies in preclinical models. Most importantly, as a result of these and other encouraging preclinical findings of therapeutic value this first-in-class, highly selective Axl inhibitor has entered the clinical trial phase. Docetaxel, the main chemotherapeutic drug used in aggressive prostate cancer treatment, has shown limited efficacy against metastatic PCa, primarily due to invariable development of drug resistance, necessitating a thorough investigation of the mechanisms underlying this drug resistance and the development of novel, more efficacious therapies to prevent or overcome resistance. Preliminary data from our laboratory provide strong evidence for the notion that Axl plays a pivotal role in resistance to docetaxel and possibly cabazitaxel treatment. Importantly, Axl inhibitor R428 enhances docetaxel efficacy. Citation Format: Luiz F. Zerbini. Emerging signaling pathways in prostate cancer therapy [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA22.
Arterial Thrombotic Events in CML Patients Treated with First-Line Nilotinib: Incidence, Management and Impact on the Long Term Outcome - a Gimema CML WP Analysis
Authors: Gabriele Gugliotta, Fausto Castagnetti, Massimo Breccia, Mariella D'adda, Fabio Stagno, Luciano Levato, Angelo Michele Carella, Bruno Martino, Mario Tiribelli, Carmen Fava, Antonella Gozzini, Marzia Salvucci, Michele Cedrone, Elena Trabacchi, Emilio Usala, Anna Rita Scortechini, Luigia Luciano, Simona Soverini, Michele Cavo, Giovanni Martinelli, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, Gianantonio Rosti
Journal: Blood (2017)
Abstract 14768: The Cortisol-to-acth Ratio, a Possible Marker of Relative Corticosteroid Insufficiency, is a Prognostic Predictor in Acute Decompensated Heart Failure
Authors: Rika Kawakami, Yasuki Nakada, Tomoya Ueda, Hiroyuki Okura, Yoshihiko Saito
Journal: Circulation (2016)

Background: Clinical significance of diminished cortisol response to adrenocorticotrophic hormone (ACTH) is not clear in acute decompensated heart failure (ADHF). Therefore, we evaluated the progno...