tbuckley/cabot-search huggingface dataset:
Prophylactic angiographic embolisation after endoscopic control of bleeding to high-risk peptic ulcers: a randomised controlled trial
Authors: James Y W Lau, Rapat Pittayanon, Ka-Tak Wong, Nutcha Pinjaroen, Philip Wai Yan Chiu, Rungsun Rerknimitr, Ingrid Lisanne Holster, Ernst J Kuipers, Kai-Chun Wu, Kim W L Au, Francis K L Chan, Joseph J Y Sung
Journal: Gut (2018)

Objectives In the management of patients with bleeding peptic ulcers, recurrent bleeding is associated with high mortality. We investigated if added angiographic embolisation after endoscopic haemostasis to high-risk ulcers could reduce recurrent bleeding. Design After endoscopic haemostasis to their bleeding gastroduodenal ulcers, we randomised patients with at least one of these criteria (ulcers≥20 mm in size, spurting bleeding, hypotensive shock or haemoglobin&lt;9 g/dL) to receive added angiographic embolisation or standard treatment. Our primary endpoint was recurrent bleeding within 30 days. Results Between January 2010 and July 2014, 241 patients were randomised (added angiographic embolisation n=118, standard treatment n=123); 22 of 118 patients (18.6%) randomised to angiography did not receive embolisation. In an intention-to-treat analysis, 12 (10.2%) in the embolisation and 14 (11.4%) in the standard treatment group reached the primary endpoint (HR 1.14, 95% CI 0.53 to 2.46; p=0.745). The rate of reinterventions (13 vs 17; p=0.510) and deaths (3 vs 5, p=0.519) were similar. In a per-protocol analysis, 6 of 96 (6.2%) rebled after embolisation compared with 14 of 123 (11.4%) in the standard treatment group (HR 1.89, 95% CI 0.73 to 4.92; p=0.192). None of 96 patients died after embolisation compared with 5 (4.1%) deaths in the standard treatment group (p=0.108). In a posthoc analysis, embolisation reduced recurrent bleeding only in patients with ulcers≥15 mm in size (2 (4.5%) vs 12 (23.1%); p=0.027). Conclusions After endoscopic haemostasis, added embolisation does not reduce recurrent bleeding. Trial registration number NCT01142180 .
Retrospective study of postoperative chemoradiation of cholangiocarcinoma in South Korea: Efficacy, side effect, and prognostic factors.
Authors: Guk Jin Lee, Jong Hoon Lee, Sung Hwan Kim, Byoung Yong Shim
Journal: Journal of Clinical Oncology (2018)

486 Background: There is no estabilished consensus about chemoradiation therapy for resected cholangiocarcinoma, and many studies are ongoing. We tried to cofirm the effectiveness and side effects of chemoradiation after operation of cholangiocarcinoma and find the prognostic factors. Methods: We found the patients with cholangiocarcinoma who receieved chemoradiation after surgery between 2002 and 2015 from two hospitals in South Korea. We checked the baseline chareacteristics, efficacy and toxicities. And we tried to identify the prognostic factors for recurrence by statistical anaylsis. Results: We retrospectivally studied 51 cholangiocarcinoma patients. Median age was 64 (range 48-83), and Men was 30 patients (58.8%) of them. By location, there were 10 (19,6%) intrahepatic cholangiocarcinomas, 13 (25.5%) hilar cholangiocarcinoma, and 28 (54.9%) extrahepatic cholangiocarcinomas. All patient received 5-FU chemoradiation after surgery. R0 resections were 31 (60.8%), R1 resections were 20 (39.2%) There was recurrence with 35 (68.6%) patients. Median relapse free survival was 292 (range 86-1769) days. Locoregional recurrence were 16 (31.4%), and distant recurrences were 26 (51.0%). For hematological toxicity, the patients showed grade 3 toxicities, as leukopenia 5 (9.8%), anemia 1 (2.0%) , thrombocytopenia 1 (2.0%). For non-hematological toxicities, there were G3 toxicities as Infection 2 (4.0%), nausea/vomiting 1 (2.0%), Adhesive ileus 1 (2.0%), bleeding 1 (2.0%). For multivariate analysis, Tumor site (HR 1.88 (95% CI 1.09-3.23). P = 0.022) and modality of radiation therapy (HR 13.27 (95% CI, 3.56-49.50)), P &lt; 0.001) were statistically meaningful factors. Conclusions: Although this is a retrospective study, we found that the result of chemoradiation therapy for some patients showed good efficacy and tolerable toxicity. We could consider chemoradiation for adjuvant therapy in cholangiocarcinoma, especially for extrahepatic cholangiocarcinoma. And intensity-modulated radiation therapy should be performed than three-dimensional radiation therapy in cholangiocarcinoma.
Management of cardiogenic shock complicating myocardial infarction
Authors: Alexandre Mebazaa, Alain Combes, Sean van Diepen, Alexa Hollinger, Jaon N. Katz, Giovanni Landoni, Ludhmila Abrahao Hajjar, Johan Lassus, Guillaume Lebreton, Gilles Montalescot, Jin Joo Park, Susanna Price, Alessandro Sionis, Demetris Yannopolos, Veli-Pekka Harjola, Bruno Levy, Holger Thiele
Journal: Intensive Care Medicine (2018)
Risk-Imaging Mismatch in Cardiac Imaging Practices for Women Receiving Systemic Therapy for Early-Stage Breast Cancer: A Population-Based Cohort Study
Authors: Paaladinesh Thavendiranathan, Husam Abdel-Qadir, Hadas D. Fischer, Ying Liu, Ximena Camacho, Eitan Amir, Peter C. Austin, Douglas S. Lee
Journal: Journal of Clinical Oncology (2018)

To assess prechemotherapy cardiac imaging practices in relation to patients' heart failure (HF) risk.We performed a population-based retrospective cohort study of women receiving chemotherapy for early-stage breast cancer in Ontario between 2007 and 2012. We surveyed for baseline cardiac imaging 6 months before chemotherapy or within 30 days thereafter. The proportion of patients who underwent imaging and cumulative incidence of major adverse cardiac event (MACE) rates was determined based on chemotherapy regimen and HF risk factors. Logistic regression was used to assess predictors of pretreatment cardiac imaging.We studied 18,444 women who had been treated with chemotherapy (median age, 55 years). There was near-universal imaging of women treated with trastuzumab-containing regimens, including those without additional HF risk factors. Women who received anthracyclines without trastuzumab underwent imaging more frequently if they had additional HF risk factors (73.3% v 62.6%; P < .001). The 5-year incidence of MACE was two to six times higher in patients with HF risk factors across all treatment regimens. Patients with HF risk factors who received anthracyclines without trastuzumab had a higher 5-year incidence of MACE (4.5%) than patients without HF risk factors who received trastuzumab without anthracyclines (2.6%). However, cardiac imaging was less frequent in the former group (73.3% v 93.6%; P < .001). Logistic regression indicated that most variation in baseline imaging was related to chemotherapy, followed by physician-level factors. The odds of imaging were doubled with female physicians. Patient-specific factors, including HF risk factors, made minimal contribution to variation in imaging.Baseline cardiac imaging was driven by chemotherapy regimen rather than HF risk. This risk-imaging mismatch is an impetus to reconsider current cardiac imaging practices in patients who receive chemotherapy for breast cancer.
Half-Dose Photodynamic Therapy versus High-Density Subthreshold Micropulse Laser Treatment in Patients with Chronic Central Serous Chorioretinopathy
Authors: Elon H.C. van Dijk, Sascha Fauser, Myrte B. Breukink, Rocio Blanco-Garavito, Joannes M.M. Groenewoud, Jan E.E. Keunen, Petrus J.H. Peters, Greet Dijkman, Eric H. Souied, Robert E. MacLaren, Giuseppe Querques, Susan M. Downes, Carel B. Hoyng, Camiel J.F. Boon
Journal: Ophthalmology (2018)

To compare the anatomic and functional efficacy and safety of half-dose photodynamic therapy (PDT) versus high-density subthreshold micropulse laser (HSML) treatment in patients with chronic central serous chorioretinopathy (cCSC).
Maintenance of skin clearance with ixekizumab treatment of psoriasis: Three-year results from the UNCOVER-3 study
Authors: Craig Leonardi, Catherine Maari, Sandra Philipp, Orin Goldblum, Lu Zhang, Nicole Burkhardt, Susan Ball, Lotus Mallbris, Pablo Gonzalez, Pablo Fernández-Peñas, Luis Puig
Journal: Journal of the American Academy of Dermatology (2018)
Characterization of Hepatocellular Carcinoma Patients with &lt;b&gt;&lt;i&gt;FGF19&lt;/i&gt;&lt;/b&gt; Amplification Assessed by Fluorescence in situ Hybridization: A Large Cohort Study
Authors: Hyo Jeong Kang, Farhan Haq, Chang Ohk Sung, Jene Choi, Seung-Mo Hong, Soo-Heang Eo, Hui Jeong Jeong, Jinho Shin, Ju Hyun Shim, Han Chu Lee, Jihyun An, Mi-Ju Kim, Kyu-pyo Kim, Sung-Min Ahn, Eunsil Yu
Journal: Liver Cancer (2018)

FGF19 amplification is a relatively novel type of genetic aberration that has been proposed to be a driver of hepatocarcinogenesis. Selective inhibitors of FGFR4, a receptor of FGF19, have been developed as targeted therapies for hepatocellular carcinoma (HCC). Despite the role of FGF19 in mediating HCC progression, the clinicopathological characterization of patients exhibiting FGF19 amplification remains unclear. Immunohistochemical staining is the simplest and most widely used method of identifying aberrations in the FGF19 gene, although its specificity is very low.This study investigated the prognostic significance of FGF19 amplification in a large cohort of 989 HCC patients using fluorescence in situ hybridization (FISH), which has a high degree of specificity. In addition, FISH data from formalin-fixed, paraffin-embedded sections were compared with copy number variation (CNV) data obtained from fresh frozen sections to validate the use of FISH as a diagnostic tool.FGF19 amplifications were detected by FISH in 51 (5.15%) of the 989 patients, and were independently associated with poor survival and a higher risk of tumor recurrence, as well as with poor prognostic factors such as a high α-fetoprotein level, hepatitis B or C virus infection, a large tumor size, microvascular invasion, and necrosis. In addition, FGF19 amplification was associated with TP53 mutation, and was mutually exclusive with CTNNB1 mutation. The results of the FISH and CNV analyses exhibited a significant concordance rate of 96% (κ = 0.618, p < 0.001).These data indicate that FGF19 amplification represents a unique molecular subtype associated with poor prognostic characteristics, which supports the hypothesis that the FGF19-FGFR4 signaling pathway plays an important role in hepatocarcinogenesis. We have also demonstrated that FISH is a viable alternative to CNV analysis, offering a number of advantages in the clinical setting.
Abstract A39: Modeling organelle-specific O-glycosylation in driving liver tumor growth, invasion, and metastasis
Authors: Anh Tuan Nguyen, Frederic Bard
Journal: Cancer Research (2018)

Abstract Cancer progression is driven by the ability of tumor cells to invade surrounding tissues. Invasiveness correlates with perturbation of a covalent modification of cell surface proteins: O-glycosylation. However, the underlying molecular mechanisms are still unclear. Here, we show that O-glycosylation initiating enzymes are activated during liver tumor growth by intracellular relocation from Golgi to ER. In a Nras/shp53 mouse liver cancer model, coexpressing an ER-targeted glycosyl-transferase GALNT1 (ER-G1) massively increased tissue growth, invasion, and metastases. ER-G1, but not its Golgi-localized counterpart, strongly stimulates glycosylation of the key cancer matrix metalloprotease MT1-MMP, this modification being essential for collagenase activity. Conversely, expression of an ER-targeted inhibitor of GALNTs inhibits liver tumor progression in Nras/shp53-injected mice. In summary, our model comprehensively demonstrates the generation and analyses of the GALA (GALNTs Activation) pathway driving liver tumor invasiveness; thus, further characterization of glycosylation substrates will unveil mechanisms of tumor growth and help identify potential therapeutic targets in human liver cancer. Citation Format: Anh Tuan Nguyen, Frederic Bard. Modeling organelle-specific O-glycosylation in driving liver tumor growth, invasion, and metastasis [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A39.
Child obesity: government considers new direct interventions
Authors: Adrian O’Dowd
Journal: BMJ (2018)

The government may implement further direct interventions to tackle childhood obesity along the lines of the sugar levy on soft drinks, a parliamentary committee has heard.

At an evidence session of the parliamentary health and social care committee’s inquiry into childhood obesity held on 22 May, ministers and officials hinted that stronger steps may be taken.

The committee’s inquiry precedes the expected launch of the next chapter of the government’s Childhood Obesity: A Plan for Action ,1 due later this year.

During the session, MPs on the committee focused on the newly published findings of a report from Public Health England (PHE),2 which showed that retailers and manufacturers had reduced sugar in foodstuffs …
Cholera Epidemic — Lusaka, Zambia, October 2017–May 2018
Authors: Nyambe Sinyange, Joan M. Brunkard, Nathan Kapata, Mazyanga Lucy Mazaba, Kunda G. Musonda, Raymond Hamoonga, Muzala Kapina, Fred Kapaya, Lwito Mutale, Ernest Kateule, Francis Nanzaluka, James Zulu, Chileshe Lukwesa Musyani, Alison V. Winstead, William W. Davis, Hammad S. N’cho, Nelia L. Mulambya, Patrick Sakubita, Orbie Chewe, Sulani Nyimbili, Ezinne V.C. Onwuekwe, Nedghie Adrien, Anna J. Blackstock, Travis W. Brown, Gordana Derado, Nancy Garrett, Sunkyung Kim, Sydney Hubbard, Amy M. Kahler, Warren Malambo, Eric Mintz, Jennifer Murphy, Rupa Narra, Gouthami G. Rao, Margaret A. Riggs, Nicole Weber, Ellen Yard, Khozya D. Zyambo, Nathan Bakyaita, Namani Monze, Kennedy Malama, Jabbin Mulwanda, Victor M. Mukonka
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

On October 6, 2017, an outbreak of cholera was declared in Zambia after laboratory confirmation of Vibrio cholerae O1, biotype El Tor, serotype Ogawa, from stool specimens from two patients with acute watery diarrhea. The two patients had gone to a clinic in Lusaka, the capital city, on October 4. Cholera cases increased rapidly, from several hundred cases in early December 2017 to approximately 2,000 by early January 2018 (Figure). In collaboration with partners, the Zambia Ministry of Health (MoH) launched a multifaceted public health response that included increased chlorination of the Lusaka municipal water supply, provision of emergency water supplies, water quality monitoring and testing, enhanced surveillance, epidemiologic investigations, a cholera vaccination campaign, aggressive case management and health care worker training, and laboratory testing of clinical samples. In late December 2017, a number of water-related preventive actions were initiated, including increasing chlorine levels throughout the city's water distribution system and placing emergency tanks of chlorinated water in the most affected neighborhoods; cholera cases declined sharply in January 2018. During January 10-February 14, 2018, approximately 2 million doses of oral cholera vaccine were administered to Lusaka residents aged ≥1 year. However, in mid-March, heavy flooding and widespread water shortages occurred, leading to a resurgence of cholera. As of May 12, 2018, the outbreak had affected seven of the 10 provinces in Zambia, with 5,905 suspected cases and a case fatality rate (CFR) of 1.9%. Among the suspected cases, 5,414 (91.7%), including 98 deaths (CFR = 1.8%), occurred in Lusaka residents.
The Dynamical Regime of Sensory Cortex: Stable Dynamics around a Single Stimulus-Tuned Attractor Account for Patterns of Noise Variability
Authors: Guillaume Hennequin, Yashar Ahmadian, Daniel B. Rubin, Máté Lengyel, Kenneth D. Miller
Journal: Neuron (2018)

Correlated variability in cortical activity is ubiquitously quenched following stimulus onset, in a stimulus-dependent manner. These modulations have been attributed to circuit dynamics involving either multiple stable states ("attractors") or chaotic activity. Here we show that a qualitatively different dynamical regime, involving fluctuations about a single, stimulus-driven attractor in a loosely balanced excitatory-inhibitory network (the stochastic "stabilized supralinear network"), best explains these modulations. Given the supralinear input/output functions of cortical neurons, increased stimulus drive strengthens effective network connectivity. This shifts the balance from interactions that amplify variability to suppressive inhibitory feedback, quenching correlated variability around more strongly driven steady states. Comparing to previously published and original data analyses, we show that this mechanism, unlike previous proposals, uniquely accounts for the spatial patterns and fast temporal dynamics of variability suppression. Specifying the cortical operating regime is key to understanding the computations underlying perception.
Correction to: miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a
Authors: Man-Qing Cao, A-Bin You, Xiao-Dong Zhu, Wei Zhang, Yuan-Yuan Zhang, Shi-Zhe Zhang, Kei-wei Zhang, Hao Cai, Wen-Kai Shi, Xiao-Long Li, Kang-Shuai Li, Dong-Mei Gao, De-Ning Ma, Bo-Gen Ye, Cheng-Hao Wang, Cheng-Dong Qin, Hui-Chan Sun, Ti Zhang, Zhao-You Tang
Journal: Journal of Hematology & Oncology (2018)

The original article [1] contains an error in Fig. 5a whereby the Western blot bands representing CyclinD1 have mistakenly been duplicated over the Western blot bands intended to represent SGK.
Adjunctive everolimus for children and adolescents with treatment-refractory seizures associated with tuberous sclerosis complex: post-hoc analysis of the phase 3 EXIST-3 trial
Authors: Paolo Curatolo, David N Franz, John A Lawson, Zuhal Yapici, Hiroko Ikeda, Tilman Polster, Rima Nabbout, Petrus J de Vries, Dennis J Dlugos, Jenna Fan, Antonia Ridolfi, Diana Pelov, Maurizio Voi, Jacqueline A French
Journal: The Lancet Child & Adolescent Health (2018)
Pharmacological evaluation of Gemcitabine administered as fixed-dose-rate in combination with cisplatin to patients with non-small-cell lung cancer
Authors: Massimo Zucchetti, Orazio Caffo, Antonio Santo, Samuela Binato, Marco Zaffaroni, Maurizio Centonze, Antonio Lucenti, Monica Giovannini, Giuseppe Cartei, Gianluigi Cetto, Maurizio D’Incalci, Enzo Galligioni
Journal: Cancer Research (2004)

5405   Gemcitabine is a fluorine deoxycitidine analog that has shown clinical activity against several solid tumor including ovarian cancer, pancreatic cancer and in non-small-cell lung cancer (NSCLC) when combined with cisplatin (DDP). Gemcitabine is a pro-drug that requires for its activity, intracellular activation to triphosphate form (dFdCTP). Gemcitabine is rapidly deactivated in plasma by cytidine deaminase to 2’,2’-difluorodeoxycitidine (dFdU). Previous studies demonstrated that the achievement of a threshold value of plasma concentration of Gemcitabine superior to 10 μM is crucial to obtain intracellular accumulation of dFdCTP. Prolonged infusion of Gemcitabine at fixed dose rate (FDR) of 10 mg/m2/min compared with standard 30min infusion are able to maintain for a longer period the above mentioned critical plasma concentration, increasing at maximal levels the rate of accumulation of the active metabolite dFdCTP. In order to evaluate the pharmacological profile of Gemcitabine administered as FDR infusion in NSCLC patients treated in combination with DDP, we designed a dose-finding and pharmacokinetic study. Gemcitabine was administered at FDR of 10 mg/m2/min at doses ranging between 600 and 1200 mg/m2 on day 1 and 8, with 75 mg/m2 of DDP on day 8. Blood samples were collected on day 1 and 8 during the infusions and up to 24 hours. Drug and dFdU plasma levels were determined by HPLC/MS/MS (LOQ 10 ng/ml). Pharmacokinetic results obtained in 22 patients revealed that DDP does not affect Gemcitabine pharmacokinetics. The target plasma concentration of 10μM was achieved in 70% of the 12 patients treated with 600-900 mg/m2 (range 10.1-17.5 μM), but surprisingly in only 40% of the 10 patients treated with 1000-1200 mg/m2 (range 7.5-12.7 μM). These data were in accord with the observation made after 3 cycles, that the majority of the responses (8/13) were obtained with the dose 600-900 mg/m2 and that the treatment was well tolerated even at the higher doses of 1000-1200 mg/m2. Further pharmacokinetic studies that involve also the measure of dFdCTP are in progress to define the optimal schedule of Gemcitabine administration as FDR infusion. (Partially supported by Eli Lilly Italia).
Abstract A40: Twist1 activation in muscle progenitor cells during development or adulthood causes severe muscle loss reminiscent of human cancer cachexia
Authors: Parash Parajuli, Santosh Kumar, Audrey Loumaye, Purba Singh, Sailaja Eragamreddy, Thien Ly Nguyen, Seval Ozkan, Mohammed S. Razzaqe, Céline Prunier, Jean-Paul Thissen, Azeddine Atfi
Journal: Cancer Research (2018)

Abstract Cancer cachexia is characterized by extreme skeletal muscle loss that results in high morbidity and mortality. The incidence of cachexia varies among tumor types, being lowest in sarcomas, whereas 90% of pancreatic ductal adenocarcinoma (PDAC) patients experience severe weight loss. How these tumors trigger muscle depletion is still unfolding. Serendipitously, we found that overexpression of Twist1 in mouse muscle progenitor cells, either constitutively during development or inducibly in adult animals, caused severe muscle atrophy with features reminiscent of cachexia. Using several genetic mouse models of PDAC, we detected a massive increase in Twist1 expression in muscle undergoing cachexia. In cancer patients, elevated levels of Twist1 are associated with greater degrees of muscle wasting. Both genetic and pharmacologic inactivation of Twist1 in muscle progenitor cells afforded substantial protection against cancer-mediated cachexia, which translated into meaningful survival benefits, implicating Twist1 as a possible target for attenuating muscle cachexia in cancer patients. Citation Format: Parash Parajuli, Santosh Kumar, Audrey Loumaye, Purba Singh, Sailaja Eragamreddy, Thien Ly Nguyen, Seval Ozkan, Mohammed S. Razzaqe, Céline Prunier, Jean-Paul Thissen, Azeddine Atfi. Twist1 activation in muscle progenitor cells during development or adulthood causes severe muscle loss reminiscent of human cancer cachexia [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A40.
Importance of pharmacology to avoid complications with endoscopic sedation
Authors: Fernando Martins do Vale, Diogo Ferreira Marques
Journal: Gut (2018)

The work of Behrens et al 1 is an interesting prospective study about sedation-related complications during GI endoscopic procedures, which by the large number of patients involved allows a reliable analysis of their rates and associated risk factors. Major complications occurred more frequently on sedated patients (0.01%) than on non sedated patients (0.007%), with a mortality rate of 0.004% with sedation and only 0.002% without sedation. The majority of complications were respiratory, and of the 38 patients with major complications, 26 required intubation and 13 died.1 It may be useful to look over the pharmacological properties of the selected drugs as a way to predict and avoid adverse outcomes, especially respiratory failure.

The majority of authors use benzodiazepines (midazolam) or propofol, which are GABAergic drugs able to induce a dose-dependent depression of …