tbuckley/cabot-search huggingface dataset:
Лечение аутоиммунного гепатита на основе национальных, международных рекомендаций и собственного опыта
Authors: Yu.M. Stepanov, S.V. Kosynska
Journal: GASTROENTEROLOGY (2019)

Аутоиммунный гепатит (АИГ) — редкая патология печени, но в последние годы количество больных увеличивается. Нет однозначного определения и четких патогномоничных критериев АИГ, отличительными признаками являются наличие аутоантител, значительная гипергаммаглобулинемия, характерные морфологические изменения и хороший ответ на иммуносупрессивную терапию. Иммуносупрессивная терапия при АИГ направлена на купирование аутоиммунного процесса, ликвидацию воспалительного синдрома, уменьшение прогрессирования фиброза, торможение развития цирроза. Препаратами первой линии являются кортикостероиды и азатиоприн, эффективность которых значительно превышает плацебо. Преднизолон назначают в среднем 40–60 мг/сут, в дозе 0,5–1 мг/кг/сут. Чем выше активность цитолиза, тем большая доза преднизолона необходима. При уменьшении цитолиза, по данным печеночных проб, соответственно уменьшается доза преднизолона. В практике чаще используется метилпреднизолон. Азатиоприн назначают или сразу, или через 2 недели приема преднизолона в дозе 50 мг/сут с возможным повышением до 100 мг/сут, в индивидуальной дозе — 1–2 мг/кг/сут. В настоящее время преимущество отдают комбинированной терапии преднизолоном и азатиоприном. Оценка эффективности лечения АИГ предусматривает контроль уровня аминотрансфераз (прежде всего аланинтрансферазы) и IgG, желательна их полная нормализация. Для оценки фиброза применяется эластография печени. К сожалению, лечение фактически назначается пожизненно. К препаратам второй линии относятся микофенолата мофетил, циклоспорин, такролимус, сиролимус, эверолимус и другие. Из них наиболее изученным считается микофенолата мофетил. Продолжаются поиски эффективной терапии АИГ, разрабатываются методы клеточной, антицитокиновой, антифибротической терапии. Приведены клинические примеры из собственного опыта. Выводы. Лечение АИГ является сложным процессом. В решении данной проблемы значительно помогают современные рекомендации, данные проведенных исследований и накопленный опыт. Выбор терапии требует индивидуального подхода с учетом особенностей клинического течения и ответа на терапию.
Clinic and pathologic features of colorectal cancer in patients less than or equal to 30 years of age.
Authors: Wen-zhuo He, Liang-ping Xia
Journal: Journal of Clinical Oncology (2015)

e14591 Background: Early-onset colorectal cancer is rare. The aim of this study is to characterize those patients. Methods: Medical records of 5212 colorectal cancer patients were reviewed referred to Sun yat-sen university cancer center between 2003 and 2012. 188 patients aged less than or equal to 30 years were identified. Further clinical and pathologic features were assessed. Results: 109 (58.0%) male and 79 (42.0%) female were included. The most common symptoms were hematochezia or melena, abdominal pain and change in bowel habits. Median duration of symptoms was 5 months (range from 2 days to 60 months). 11 (5.9%) patients presented with acute intestinal obstruction. 15 (8.0%) patients had a positive family history. The distribution of primary tumors were as follows- 37 (19.7%) located at ascending colon, 7 (3.7%) at transverse colon, 36 (19.1%) at descending colon, 39 (20.7%) at sigmoid and 67 (35.6%) at rectum. Median size of primary tumor was 4.8 cm (range from 1.0 to 20.0 cm). Mucinous adenocacinoma were found in 56 (29.8%) patients. At presentation, 40 (21.3%) patients were stage I+II, 70 (37.2%) were stage III and 78 (41.5%) had distant metastases. The most common metastatic sites were intraperitoneal dissemination (27.7%), liver (20.7%) and lung (7.4%). Median overall survival of stage I+II, III and IV patients were 54.1, 40.7 and 20.9 months, respectively. Conclusions: Initial symptoms of early-onset colorectal cancer are similar as adult. The notably higher proportion of intraperitoneal dissemination and lower frequency of right colon cancer suggest the biology of early-onset colorectal cancer is different. Characteristic No. % Gender Male 109 58.0 Female 79 42.0 Age, years 10-15 5 2.6 16-20 11 5.9 20-25 51 27.1 26-30 121 64.4 Tumor site Ascending colon 37 19.7 Transverse colon 7 3.7 Descending colon 36 19.1 Sigmoid 39 20.7 Rectum 67 35.6 Multiple 2 1.1 Histologic type Mucinous 56 29.8 Nonmucinous 132 70.2 Differentiation Poorly 93 49.5 Moderately 92 48.9 Well 3 1.6 T stage 1 2 1.0 2 10 5.3 3 66 35.1 4 77 41.0 x 33 17.6 N stage 0 51 27.1 1 42 22.3 2 60 31.9 x 35 18.7 Stage I 2 1.0 II 38 20.3 III 70 37.2 IV 78 41.5 CEA level (ng/ml) ≤ 5 91 48.4 ＞5 97 51.6 CA199 level (U/ml) ≤ 35 111 59.0 ＞35 77 41.0
Possibility of a Risk-Adapted Treatment Strategy for Untreated Aggressive Adult T-Cell Leukemia-Lymphoma (ATL) Based on the ATL Prognostic Index: A Supplementary Analysis of the JCOG9801 Study
Authors: Kosuke Toyoda, Kunihiro Tsukasaki, Ryunosuke Machida, Tomohiro Kadota, Takuya Fukushima, Kenji Ishitsuka, Dai Maruyama, Hirokazu Nagai
Journal: Blood (2018)
Reply
Authors: Eduardo Vilar‐Gomez, Naga Chalasani
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. We appreciate Jian He and Leng Ai‐Min for their interest in our study published in hepatology.1 First, they bring up the possibility that patients included in our report may have consumed certain over‐the‐counter hepatoprotective agents (e.g., glutathione, diammonium glycyrrhizinate, or polyene phosphatidyl choline) as antioxidants to improve their liver health and that such use may have confounded our study results. We agree that it is a possibility, but at our center, which is located in the midwestern United States, awareness among our patients that oxidative stress may have an important role in the pathogenesis of nonalcoholic steatohepatitis and its progression is not high. But this is an important concern for some parts of the world where there is higher use of complementary and alternative medications. Second, they point out that some patients who were included in our vitamin E group purchased their vitamin E over the counter rather through a pharmacy. We would like to clarify that while some patients may have obtained their vitamin E over the counter, it was under a treating physician's direction. Having said that, it remains possible that compliance with long‐term use of vitamin E may have been influenced by higher motivation, which may be associated with a healthier lifestyle. Our nonrandomized study carries a number of limitations, and hence our preliminary but promising observations need to be confirmed in a randomized, double‐blind, placebo‐controlled trial.
WHO’s Top Health Threats for 2019
Authors: M.J. Friedrich
Journal: JAMA (2019)

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LINE1 Derepression in Aged Wild-Type and SIRT6-Deficient Mice Drives Inflammation
Authors: Matthew Simon, Michael Van Meter, Julia Ablaeva, Zhonghe Ke, Raul S. Gonzalez, Taketo Taguchi, Marco De Cecco, Katerina I. Leonova, Valeria Kogan, Stephen L. Helfand, Nicola Neretti, Asael Roichman, Haim Y. Cohen, Margarita V. Meer, Vadim N. Gladyshev, Marina P. Antoch, Andrei V. Gudkov, John M. Sedivy, Andrei Seluanov, Vera Gorbunova
Journal: Cell Metabolism (2019)
Abstract 042: Accelerometer-Derived Daily Life Movement Classified by Machine-Learning and Incidence of Cardiovascular Disease in Older Women: The OPACH Study
Authors: Andrea Z LaCroix, John Bellettiere, Chongzhi Di, Dori Rosenberg, Michael J LaMonte
Journal: Circulation (2019)

Background: OPACH study evidence has shown that both accelerometer-measured light (LPA) and moderate-vigorous physical activity (MVPA) are associated with CVD mortality and morbidity in older women. However, accelerometer-measured PA exposures have been limited to measuring time and intensity of movement, without providing any information about which physical activity behaviors produced the movements. This study examines associations of a validated, machine-learned classification of “daily life movement” (DLM) in relation to incident CVD events. Methods: Women (n=5416, mean age=79±7, 33% Black, 17% Hispanic) without prior myocardial infarction or stroke wore accelerometers for up to 7 days from May 2012-April 2014 and were followed for incident CVD through February 2018 (n=667 events). Machine-learned algorithms were developed in a sample of 39 free-living older women who simultaneously wore small cameras (SenseCam) capturing images of daily activities (used as the ground truth) and hip-worn accelerometers to measure movement. DLM was defined as standing and moving in a confined space such as around the house or garden. The DLM algorithm had 66% sensitivity and 94% specificity compared to SenseCam images and was further validated in 2 other populations. Cox models estimated hazard ratios (HR) and 95% confidence intervals for CVD across quartiles of DLM adjusting for age, race-ethnicity, smoking, alcohol use, education, co-morbidity score, physical function, and self-rated health. We then examined the DLM association with CVD after adjustment for MVPA. Results: Fully-adjusted HRs (95% CIs) for CVD across DLM quartiles were: [Q1-ref 1.00 ; Q2 0.74 (0. 60,0.91); Q3 0.76 (0.61,0.94); Q4 0.56 (0.44,0.72); p-trend&lt;0.001]. Hazard ratios for continuous DLM show that associations were independent of MVPA (Figure). Conclusions: Older women who spend more time in DLM had reduced risks of incident CVD. Increasing levels of DLM is an achievable behavioral target for reducing CVD risk in older women.
Trends in obesity and comorbid illness in African American and Caucasian females treated for breast cancer.
Authors: Allison Honart West, Zakiya Franklin, Melinda Stolley, Susan Hong
Journal: Journal of Clinical Oncology (2015)

e12642 Background: Epidemiological estimates demonstrate that there are more than 2.8 million breast cancer survivors in the U.S. One quarter of these survivors are obese; and African American (AA)...
Do serum nectin-2 levels have a prognostic effect in patients with colorectal cancer?
Authors: Mert Basaran, Senem Karabulut, Mehmet Karabulut, Meral Gunaldi, Halil Alis, Kayhan Ertürk, Sezai Vatansever, Burak Sakar, Nuri Faruk Aykan
Journal: Journal of Clinical Oncology (2015)

e14531 Background: Nectins are a family of integral protein and immunoglobulin-like cell adhesion molecules involved in the formation of functioning adherence and tight junctions. Aberrant expression is associated with cancer progression, apoptosis and cell proliferation but little is known how these effects change in cell behavior. The objective of this study was to evaluate the serum levels of nectin-2 in regard to diagnostic, predictive and prognostic value in colorectal cancer (CRC) patients. Methods: One hundred forty CRC patients were enrolled into this study. Pre-treatment serum nectin-2 levels were determined by enzyme-linked immunosorbent assay ( ELISA) method. Age- and sex-matched 40 healthy controls were included in the analysis. Results: Median age of patients was 60 years old, range 24 to 84 years. The localization of tumor in majority of the patients was colon (n = 81, 58%). Median follow-up time was 14 months while forty-three (31%) patients experienced disease progression, thirty-one (22%)of the remaining patients died. The number of patients who received neoadjuvant treatment and adjuvant chemotherapy (CTX) were 37, 71, respectively. Of the patients who received palliative CTX, 24 had oxaliplatin-based combination whereas 22 and 9 had irinotecan-based combination and single agent FU/capecitabine, respectively.Thirty-six and 15 of the patients who received targeted therapy had bevacizumab and cetuximab, respectively.Thirty-one percent of 55 metastatic patients who received palliative CTX were CTX-responsive. The baseline median serum nectin-2 levels were significantly higher than in the healthy control group (p < 0.001). However, known clinical variables including response to CTX were not found to be correlated with serum nectin-2 concentrations (p > 0.05). Patients with elevated serum nectin-2 concentrations had significantly unfavorable PFS compared with those with lower levels (median 5.8 v 9.1 months, respectively, p = 0.04). On the other hand, serum nectin-2 levels showed no significantly adverse effect on OS (p = 0.19). Conclusions: Serum levels of nectin-2 may have diagnostic and prognostic roles in patients with CRC.
Lentiviral Vector-Based Dendritic Cell Vaccine Suppresses HIV Replication in Humanized Mice
Authors: Thomas D. Norton, Anjie Zhen, Takuya Tada, Jennifer Kim, Scott Kitchen, Nathaniel R. Landau
Journal: Molecular Therapy (2019)

HIV-1-infected individuals are treated with lifelong antiretroviral drugs to control the infection. A means to strengthen the antiviral T cell response might allow them to control viral loads without antiretroviral drugs. We report the development of a lentiviral vector-based dendritic cell (DC) vaccine in which HIV-1 antigen is co-expressed with CD40 ligand (CD40L) and a soluble, high-affinity programmed cell death 1 (PD-1) dimer. CD40L activates the DCs, whereas PD-1 binds programmed death ligand 1 (PD-L1) to prevent checkpoint activation and strengthen the cytotoxic T lymphocyte (CTL) response. The injection of humanized mice with DCs transduced with vector expressing CD40L and the HIV-1 SL9 epitope induced antigen-specific T cell proliferation and memory differentiation. Upon HIV-1 challenge of vaccinated mice, viral load was suppressed by 2 logs for 6 weeks. Introduction of the soluble PD-1 dimer into a vector that expressed full-length HIV-1 proteins accelerated the antiviral response. The results support development of this approach as a therapeutic vaccine that might allow HIV-1-infected individuals to control virus replication without antiretroviral therapy. HIV-1-infected individuals are treated with lifelong antiretroviral drugs to control the infection. A means to strengthen the antiviral T cell response might allow them to control viral loads without antiretroviral drugs. We report the development of a lentiviral vector-based dendritic cell (DC) vaccine in which HIV-1 antigen is co-expressed with CD40 ligand (CD40L) and a soluble, high-affinity programmed cell death 1 (PD-1) dimer. CD40L activates the DCs, whereas PD-1 binds programmed death ligand 1 (PD-L1) to prevent checkpoint activation and strengthen the cytotoxic T lymphocyte (CTL) response. The injection of humanized mice with DCs transduced with vector expressing CD40L and the HIV-1 SL9 epitope induced antigen-specific T cell proliferation and memory differentiation. Upon HIV-1 challenge of vaccinated mice, viral load was suppressed by 2 logs for 6 weeks. Introduction of the soluble PD-1 dimer into a vector that expressed full-length HIV-1 proteins accelerated the antiviral response. The results support development of this approach as a therapeutic vaccine that might allow HIV-1-infected individuals to control virus replication without antiretroviral therapy.
Association of Neurosurgical Resection With Development of Pachymeningeal Seeding in Patients With Brain Metastases
Authors: Daniel N. Cagney, Nayan Lamba, Sumi Sinha, Paul J. Catalano, Wenya Linda Bi, Brian M. Alexander, Ayal A. Aizer
Journal: JAMA Oncology (2019)

Neurosurgical resection represents an important management strategy for patients with large, symptomatic brain metastases and increasingly is followed by stereotactic radiation as opposed to whole-brain radiation. Whether neurosurgical resection is associated with tumor spread beyond the resection site and adjuvant stereotactic radiation field remains unknown.To characterize the association and incidence of pachymeningeal seeding with neurosurgical resection in patients with brain metastases treated with adjuvant stereotactic radiation.Retrospective cohort study of a consecutive sample of patients with newly diagnosed brain metastases managed with neurosurgical resection and stereotactic radiation (n = 318) vs radiation alone (n = 870) between 2001 and 2015.Incidence of pachymeningeal seeding (dural and/or outer arachnoid) and leptomeningeal disease in patients treated with neurosurgical resection and stereotactic radiation vs radiation alone and the risk factors and outcomes associated with pachymeningeal seeding in patients treated with neurosurgical resection followed by stereotactic radiation.In 1188 patients with newly diagnosed brain metastases, 133 men and 185 women (mean [SD] age, 58.9 [11.5] years) underwent neurosurgical resection. Resection was found to be associated with pachymeningeal seeding (36 of 318 patients vs 0 of 870 patients; P < .001) but not leptomeningeal disease (hazard ratio [HR], 1.14; 95% CI, 0.73-1.77; P = .56). In total, 36 (8.4%) of 428 operations were complicated by pachymeningeal seeding, with a higher incidence noted with resection of previously irradiated vs unirradiated metastases (HR, 2.39; 95% CI, 1.25-4.57; P = .008). Patients with pachymeningeal seeding had relatively low rates of subsequent development of new brain metastases and leptomeningeal disease (8 [16%] of 51 and 6 [13%] of 48, respectively). Among patients with pachymeningeal seeding, neurologic death primarily owing to progressive pachymeningeal disease accounted for 26 (72%) of 36 deaths, but when treated with salvage radiation, 49.1% of patients survived 1 year or longer.In the era of omission of adjuvant whole-brain radiation after neurosurgical resection, pachymeningeal seeding beyond the stereotactic radiation field represents a notable oncologic event that often proves difficult to salvage. However, in some patients, disease control can be achieved with radiotherapeutic approaches.
Comparison of Haploidentical Transplantation with Post-Transplantation Cyclophosphamide and Umbilical Cord Blood Transplantation in Children and Adolescents with Hematologic Malignancies after Targeted Busulfan-Based Myeloablative Conditioning Using Intensive Pharmacokinetic Monitoring
Authors: Kyung Taek Hong, Hyoung Jin Kang, Hong Yul Ahn, Jung Yoon Choi, Sang Hoon Song, Kyung-Sang Yu, In-Jin Jang, Hee Young Shin
Journal: Blood (2018)
Abstract P105: Less Walkable Neighborhoods Are Associated With Worse Cardiovascular Risk Profile
Authors: Nicholas A Howell, Jack V Tu, Rahim Moineddin, Anna Chu, Gillian L Booth
Journal: Circulation (2019)

Introduction: There is mounting evidence that neighborhoods that have low levels of walkability have higher burdens of cardiovascular disease (CVD) risk factors such as obesity and hypertension. However, few studies have examined the impact of walkability on overall cardiovascular risk. Hypothesis: We hypothesized that residents living in less walkable communities have a higher burden of cardiovascular risk factors and a greater predicted risk for future CVD events. Methods: We assembled a cross-sectional sample of community dwelling adults aged 40-74 on January 1, 2008 from the CANHEART cohort. We ascertained systolic blood pressure, HDL and total cholesterol, smoking status, and diabetes status using a combination of EMR, clinical laboratory databases, and health administrative databases. The primary outcome was an estimated total 10-year cardiovascular disease risk of ≥ 7.5% using the ACC/AHA Pooled Cohort risk score. Walkability was measured using a validated index and divided into quintiles from lowest (Q1) to highest (Q5). The associations were tested using linear and logistic regression with cluster-robust standard errors, adjusting for confounders. Results: In total, 44,448 individuals were included in the analysis. Individuals living in less walkable areas had a higher predicted 10-year CVD risk than those living in highly walkable areas. The association was non-linear, as individuals living in neighborhoods of mid-range walkability (Q3) were even more likely to have an estimated 10-year CVD risk exceeding 7.5% in comparison to those in Q5 (OR = 1.33, (1.23, 1.45)). Conversely, we observed monotonic associations between decreasing walkability and higher mean systolic blood pressure (Q1 vs. Q5: +2.73 mmHg, 95% CI: +2.11, + 3.35) and odds of diabetes (Q1 vs. Q5: OR = 1.29, 95% CI: 1.13, 1.47). Dose-response associations were also observed between decreasing walkability and lower HDL cholesterol (Q1 vs. Q5: -1.93 mg/dl, 95% CI: -2.32, -1.16) and likelihood of being a current smoker (Q1 vs. Q5: OR = 0.76, 95% CI: 0.67, 0.85). Conclusions: Residents living in less walkable neighborhoods had a higher burden of CVD risk factors and a higher estimated risk of future CVD. Conversely, the likelihood of smoking was higher in more walkable neighborhoods, suggesting this may be an area to focus smoking cessation efforts.