tbuckley/cabot-search huggingface dataset:
Risk factors for 90-day readmission in veterans with inflammatory bowel disease—Does post-discharge follow-up matter?
Authors: Ashish Malhotra, Parkpoom Phatharacharukul, Charat Thongprayoon
Journal: Military Medical Research (2018)

Repeat hospitalizations in veterans with inflammatory bowel disease (IBD) are understudied. The early readmission rate and potentially modifiable risk-factors for 90-day readmission in veterans with IBD were studied to avert avoidable readmissions.A retrospective cohort study was conducted using the data from veterans who were admitted to the Minneapolis VA Medical Center (MVMC) between January 1, 2007, and December 31, 2013, for an IBD-related problem. All-cause readmissions within 30 and 90 days were recorded to calculate early readmission rates. The multivariate logistic regression was used to identify the potential risk factors for 90-day readmission.There were 130 unique patients (56.9% with Crohn's disease and 43.1% with ulcerative colitis) with 202 IBD-related index admissions. The mean age at the time of index admission was 59.8 ± 15.2 years. The median time to re-hospitalization was 26 days (IQR 10-49), with 30- and 90-day readmission rates of 17.3% (35/202) and 29.2% (59/202), respectively. Reasons for all-cause readmission were IBD-related (71.2%), scheduled surgery (3.4%) and non-gastrointestinal causes (25.4%). The following reasons were independently associated with 90-day readmission: Crohn's disease (OR 3.90; 95% CI 1.82-8.90), use of antidepressants (OR 2.19; 95% CI 1.12-4.32), and lack of follow-up within 90 days with a primary care physician (PCP) (OR 2.63; 95% CI 1.32-5.26) or a gastroenterologist (GI) (OR 2.44; 95% CI 1.20-5.00). 51.0% and 49.0% of patients had documentation of a recommended outpatient follow-up with PCP and/or GI, respectively.Early readmission in IBD is common. Independent risk factors for 90-day readmission included Crohn's disease, use of antidepressants and lack of follow-up visit with PCP or GI. Further research is required to determine if the appropriate timing of post-discharge follow-up can reduce IBD readmissions.
Margaret McCartney: Cancer patients should not be shamed
Authors: Margaret McCartney
Journal: BMJ (2018)

The charity Cancer Research UK has gone large on its publicity campaign about obesity. Bus stops and advertising hoardings are replete with black text on a white background. The adverts invite us to fill in the blanks and spell out OBESITY, asking us to “Guess what is the biggest preventable cause of cancer after smoking.”

The plain layout with warning label is reminiscent of a cigarette packet. I don’t think this is coincidental. In what Cancer Research UK itself describes as a “PR stunt,”1 the charity also created “fake cigarette packets with chips in to visually represent that obesity is the second biggest preventable …
The survival outcome, prostate-specific antigen (PSA) response and risk of fatigue of enzalutamide as first- and later-line treatment options in patients with metastatic castration-resistant prostate cancer (mCRPC): The real-world experience.
Authors: Darren M.C. Poon, Kenneth C.W. Wong, T.W. Chan, Kitty Law, Kuen Chan, Ka Chai Lee, Conrad Lee, Chan Fong Ting
Journal: Journal of Clinical Oncology (2018)

330 Background: The real-world data regarding the efficacy and toxicity, particularly fatigue, of Enzalutmide (Enza) as first and later line treatment options in mCRPC patients is currently lacking. We aimed to evaluate the survival outcome, PSA response and rate of fatigue of Enza in clinical practice outside trial setting. Methods: The clinical records of mCRPC patients treated with Enza from all 7 public oncology centers in Hong Kong between August 2015 and October 2017 were reviewed. The treatment efficacy and its determinants, and toxicities were determined. Results: A total of 117 mCRPC patients were treated with Enza, of whom 29.1%, 48.7%, 19.3% had Enza as their first (chemo-naïve), 2 nd (post-docetaxel or abiraterone) and 3 rd or above (had at least 2 of the prior followings: docetaxel, abiraterone, cabazitaxel or radium-223) line treatment options. Visceral metastases were present in 20.6/29.8/50% patients with 1 st / 2 nd / 3 rd or above line Enza. The median overall survival (OS) and progression-free survival (PFS) were not reached (1yr OS rate: 82%)/15.8/7.4 and 7.1/3.9/2.2 months for 1 st /2 nd /3 rd or above lines Enza, respectively (p = 0.0002). PSA responses ( &gt; 50% decline of PSA from baseline with Enza) were achieved in 73.5/35.1 (post-docetaxel: 53.8%/post-abiraterone: 29.5%)/19.2% patients with 1 st /2 nd /3 rd or above lines Enza (p &lt; 0.001). The presence of PSA response was associated with both favorable OS (HR 0.19; p &lt; 0.0001) and PFS (HR 0.29; p &lt; 0.001) in the multivariate analysis of whole cohort. Grade 1-2 and 3-4 fatigue was present in 44.1/59.6/57.7% and 5.9/7.0/19.2% patients with 1 st /2 nd /3 rd or above line Enza, respectively (p = 0.023). The use of 3rd or above lines of Enza is significantly associated with grade 2 or above fatigue in multivariate analysis of whole cohort (HR = 8.05; p = 0.01). Conclusions: In real-world clinical setting, more frequent PSA response, longer OS and PFS was found in chemo-naïve patients with Enza. Patients with later lines of Enza had higher risk of fatigue.
Advances in Carbon Nanotubes–Hydrogel Hybrids in Nanomedicine for Therapeutics
Authors: Arti Vashist, Ajeet Kaushik, Atul Vashist, Vidya Sagar, Anujit Ghosal, Y. K. Gupta, Sharif Ahmad, Madhavan Nair
Journal: Advanced Healthcare Materials (2018)

In spite of significant advancement in hydrogel technology, low mechanical strength and lack of electrical conductivity have limited their next-level biomedical applications for skeletal muscles, cardiac and neural cells. Host-guest chemistry based hybrid nanocomposites systems have gained attention as they completely overcome these pitfalls and generate bioscaffolds with tunable electrical and mechanical characteristics. In recent years, carbon nanotube (CNT)-based hybrid hydrogels have emerged as innovative candidates with diverse applications in regenerative medicines, tissue engineering, drug delivery devices, implantable devices, biosensing, and biorobotics. This article is an attempt to recapitulate the advancement in synthesis and characterization of hybrid hydrogels and provide deep insights toward their functioning and success as biomedical devices. The improved comparative performance and biocompatibility of CNT-hydrogels hybrids systems developed for targeted biomedical applications are addressed here. Recent updates toward diverse applications and limitations of CNT hybrid hydrogels is the strength of the review. This will provide a holistic approach toward understanding of CNT-based hydrogels and their applications in nanotheranostics.
Government won’t accept DDRB recommendations next year
Authors: Abi Rimmer
Journal: BMJ (2014)

The government has said that it will not take recommendations from the Review Body on Doctors’ and Dentists’ Remuneration (DDRB) next year.

In a letter to the DDRB, Danny Alexander, chief secretary to the Treasury, said that in 2015-16 the government intended to award all NHS staff a 1% increase to their pay.1 Earlier this year the DDRB recommended an increase in basic pay of 1% to the national salary scales for salaried doctors and dentists for 2014-15, and in March the government announced that in 2014-15 NHS staff and salaried doctors would receive …
EVALUATION OF 3 LIVER FIBROSIS MARKERS: ASPARTATE AMINOTRANSFERASE TO PLATELET RATIO (APRI), FIBROSIS-4 (FIB-4) INDEX AND TYPE IV COLLAGEN 7S (P4NP 7S) AMONG PATIENTS WITH ACUTELY DECOMPENSATED HEART FAILURE
Authors: Hiroshi Yukawa, Kazuya Nagao, Tsukasa Inada
Journal: Journal of the American College of Cardiology (2018)
Abstract P4-03-14: OTULIN promotes resistance and metastasis upon chemotherapy in TNBC by activating Wnt/β-catenin signaling
Authors: Z Wu, W Wang, B Zhang, J Xue, Y Chi, J Wu
Journal: Cancer Research (2018)

Abstract Triple-negative breast cancer (TNBC) or Basal-like breast cancer is characterized by worse prognosis than other breast cancer subtypes due to the rapid-arising therapeutic resistance accompanied by aggressive metastasis. The therapy-resistant tumor cells, including cancer stem-like cells (CSCs) with intrinsic resistance or tumor cells acquired resistance during treatments, could repopulate the primary tumors and serve as seeds for recurrent metastatic lesions. However, the molecular events orchestrating the innate and acquired therapeutic resistance are not completely understood. We found a recently identified linear ubiquitin-specific deubiquitinase OTULIN is overexpressed in breast tumors, especially in the basal-like subtype, compared with normal breast tissues. Moreover, OTULIN overexpression significantly increased TNBC cells resistance to chemotherapy and is associated with shorter RFS in breast cancer patients. Mechanistically, we found genotoxic treatments activate OTLULIN, which promotes epithelial-to-mesenchymal transition (EMT) in TNBC cells through increased activity of Wnt/β-Catenin signaling. OTULIN overexpression significantly increased TNBC cells resistance to chemodrugs while inhibiting Wnt/β-Catenin sensitized TNBC xenografts to Doxorubicin treatment in vivo. Our findings suggest that OTULIN-mediated Wnt/β-Catenin activation may increase TNBC therapeutic resistance and aggressiveness by promoting EMT. Targeting OTULIN and the chemotherapy-induced Wnt/β-Catenin activation may serves as promising strategy to mitigate drug resistance and reduce metastasis in TNBC patients receiving chemotherapy. Citation Format: Wu Z, Wang W, Zhang B, Xue J, Chi Y, Wu J. OTULIN promotes resistance and metastasis upon chemotherapy in TNBC by activating Wnt/β-catenin signaling [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-03-14.
Use doctors’ competitive nature to drive improvement, researchers say
Authors: Matthew Limb
Journal: BMJ (2016)

Team based games increase doctors’ participation in learning about quality improvement, researchers have found.

A US study found that methods such as “game mechanics” can be effective and “powerfully motivating” in leading to more learner involvement in quality improvement education. A team from the University of California Los Angeles and other institutions has published their findings in the International Journal for Quality in Health Care .1

The researchers said that the results “suggest an important role for the social context of education as a lever to …
Oncogenic Kinase–Induced PKM2 Tyrosine 105 Phosphorylation Converts Nononcogenic PKM2 to a Tumor Promoter and Induces Cancer Stem–like Cells
Authors: Zhifen Zhou, Min Li, Lin Zhang, Hong Zhao, Özgür Şahin, Jing Chen, Jean J. Zhao, Zhou Songyang, Dihua Yu
Journal: Cancer Research (2018)

The role of pyruvate kinase M2 isoform (PKM2) in tumor progression has been controversial. Previous studies showed that PKM2 promoted tumor growth in xenograft models; however, depletion of PKM2 in the Brca1-loss-driven mammary tumor mouse model accelerates tumor formation. Because oncogenic kinases are frequently activated in tumors and PKM2 phosphorylation promotes tumor growth, we hypothesized that phosphorylation of PKM2 by activated kinases in tumor cells confers PKM2 oncogenic function, whereas nonphosphorylated PKM2 is nononcogenic. Indeed, PKM2 was phosphorylated at tyrosine 105 (Y105) and formed oncogenic dimers in MDA-MB-231 breast cancer cells, whereas PKM2 was largely unphosphorylated and formed nontumorigenic tetramers in nontransformed MCF10A cells. PKM2 knockdown did not affect MCF10A cell growth but significantly decreased proliferation of MDA-MB-231 breast cancer cells with tyrosine kinase activation. Multiple kinases that are frequently activated in different cancer types were identified to phosphorylate PKM2-Y105 in our tyrosine kinase screening. Introduction of the PKM2-Y105D phosphomimetic mutant into MCF10A cells induced colony formation and the CD44hi/CD24neg cancer stem-like cell population by increasing Yes-associated protein (YAP) nuclear localization. ErbB2, a strong inducer of PKM2-Y105 phosphorylation, boosted nuclear localization of YAP and enhanced the cancer stem-like cell population. Treatment with the ErbB2 kinase inhibitor lapatinib decreased PKM2-Y105 phosphorylation and cancer stem-like cells, impeding PKM2 tumor-promoting function. Taken together, phosphorylation of PKM2-Y105 by activated kinases exerts oncogenic functions in part via activation of YAP downstream signaling to increase cancer stem-like cell properties.Significance: These findings reveal PKM2 promotes tumorigenesis by inducing cancer stem-like cell properties and clarify the paradox of PKM2's dichotomous functions in tumor progression. Cancer Res; 78(9); 2248-61. ©2018 AACR.
Dissecting the expression landscape of genitourinary cancers.
Authors: Claudio Jeldres, Sabrina Bouchard, Patrick O Richard, Michel Carmel, Robert Sabbagh, Martin Bisaillon
Journal: Journal of Clinical Oncology (2018)

573 Background: Genitourinary (GU) cancers include bladder urothelial carcinoma (BCa), prostate cancer, kidney clear cell or papillary carcinoma, uterus endometrial carcinoma, ovarian cystadenocarcinoma and testicular germ cell tumors. Clinical data show a higher prevalence of GU cancers for men than women, suggesting significant molecular differences depending on sex regarding cancer development. This project aims at dissecting the expression landscape for all GU cancers and identify significant dysregulated genes between cancer and normal tissues specific either for men and women. The resulting data will serve a clinical application consisting in targeting novel molecular biomarkers detected in urine for GU cancers early diagnosis. Methods: Based on RNAseq data provided by The Cancer Genome Atlas, gene expression fold-change for 19,123 genes from cancer tissues and normal tissues was initially compared for each GU cancer. To ensure significant gene dysregulation, only genes showing a fold-change ≤ -log2(2) or ≥ log2(2) and a p-value &lt; 0.05 were retained. Next, a comparison in gene expression modification between men and women for each cancer was made to identify the most significant molecular differences between both sexes. Unique dysregulated genes for each cancer were then identified and their presence or absence in urine was confirmed. From the pool of genes expressing proteins in urine, non-parametric tests for paired and unpaired values were used to determine the statistical difference between cancer and normal tissues in terms of gene expression. Results: Among 2880 genes significantly dysregulated for all five GU cancers, more than half of them were unique to BCa. Among these, 129 gene products (proteins) were ultimately detected in urine of patients. Seven up-regulated and ten down-regulated genes have shown high statistical differences between cancer and normal tissues in the Mann-Whitney U test for unpaired values. CEACAM6, S100A8 and S100A9 have shown significant differences in the Wilcoxon test for paired values which make them potential biomarkers ready for validation by LC-MS/MS. Conclusions: This present study shows the relevance to pursue research in gene expression modification in cancer to improve early diagnosis.
Efficacy and Safety of IDegLira Versus Basal-Bolus Insulin Therapy in Patients With Type 2 Diabetes Uncontrolled on Metformin and Basal Insulin: The DUAL VII Randomized Clinical Trial
Authors: Liana K. Billings, Ankur Doshi, Didier Gouet, Alejandra Oviedo, Helena W. Rodbard, Nikolaos Tentolouris, Randi Grøn, Natalie Halladin, Esteban Jodar
Journal: Diabetes Care (2018)

In patients with uncontrolled type 2 diabetes on basal insulin, prandial insulin may be initiated. We assessed the efficacy and safety of initiating insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus basal-bolus insulin.A phase 3b trial examined patients with uncontrolled type 2 diabetes on insulin glargine (IGlar U100) 20-50 units/day and metformin, randomized to IDegLira or IGlar U100 and insulin aspart ≤4 times per day.Glycated hemoglobin (HbA1c) decreased from 8.2% (66 mmol/mol) to 6.7% (50 mmol/mol) with IDegLira and from 8.2% (67 mmol/mol) to 6.7% (50 mmol/mol) with basal-bolus (estimated treatment difference [ETD] -0.02% [95% CI -0.16, 0.12]; -0.2 mmol/mol [95% CI -1.7, 1.3]), confirming IDegLira noninferiority versus basal-bolus (P < 0.0001). The number of severe or blood glucose-confirmed symptomatic hypoglycemia events was lower with IDegLira versus basal-bolus (risk ratio 0.39 [95% CI 0.29, 0.51]; rate ratio 0.11 [95% CI 0.08, 0.17]). Body weight decreased with IDegLira and increased with basal-bolus (ETD -3.6 kg [95% CI -4.2, -2.9]). Fasting plasma glucose reductions were similar; lunch, dinner, and bedtime self-monitored plasma glucose measurements were significantly lower with basal-bolus. Sixty-six percent of patients on IDegLira vs. 67.0% on basal-bolus achieved HbA1c <7.0% (53 mmol/mol). Total daily insulin dose was lower with IDegLira (40 units) than basal-bolus (84 units total; 52 units basal).In patients with uncontrolled type 2 diabetes on IGlar U100 and metformin, IDegLira treatment elicited HbA1c reductions comparable to basal-bolus, with statistically superior lower hypoglycemia rates and weight loss versus weight gain.
Effect of Standard vs Intensive Blood Pressure Control on Cerebral Blood Flow in Small Vessel Disease
Authors: Iain D. Croall, Daniel J. Tozer, Barry Moynihan, Usman Khan, John T. O’Brien, Robin G. Morris, Victoria C. Cambridge, Thomas R. Barrick, Andrew M. Blamire, Gary A. Ford, Hugh S. Markus
Journal: JAMA Neurology (2018)

<h3>Importance</h3> Blood pressure (BP) lowering is considered neuroprotective in patients with cerebral small vessel disease; however, more intensive regimens may increase cerebral hypoperfusion. This study examined the effect of standard vs intensive BP treatment on cerebral perfusion in patients with severe small vessel disease. <h3>Objective</h3> To investigate whether standard vs intensive BP lowering over 3 months causes decreased cerebral perfusion in small vessel disease. <h3>Design, Setting, and Participants</h3> This randomized clinical trial took place at 2 English university medical centers. Patients were randomized via a central online system (in a 1:1 ratio). Seventy patients with hypertension and with magnetic resonance imaging–confirmed symptomatic lacunar infarct and confluent white matter hyperintensities were recruited between February 29, 2012, and October 21, 2015, and randomized (36 in the standard group and 34 in the intensive group). Analyzable data were available in 62 patients, 33 in the standard group and 29 in the intensive group, for intent-to-treat analysis. This experiment examines the 3-month follow-up period. <h3>Interventions</h3> Patients were randomized to standard (systolic, 130-140 mm Hg) or intensive (systolic, &lt;125 mm Hg) BP targets, to be achieved through medication changes. <h3>Main Outcomes and Measures</h3> Cerebral perfusion was measured using arterial spin labeling; the primary end point was change in global perfusion between baseline and 3 months, compared between treatment groups by analysis of variance. Linear regression compared change in perfusion against change in BP. Magnetic resonance imaging scan analysis was masked to treatment group. <h3>Results</h3> Among 62 analyzable patients, the mean age was 69.3 years, and 60% (n = 37) were male. The mean (SD) systolic BP decreased by 8 (12) mm Hg in the standard group and by 27 (17) mm Hg in the intensive group (<i>P</i> &lt; .001), with mean (SD) achieved pressures of 141 (13) and 126 (10) mm Hg, respectively. Change in global perfusion did not differ between treatment groups: the mean (SD) change was −0.5 (9.4) mL/min/100 g in the standard group vs 0.7 (8.6) mL/min/100 g in the intensive group (partial η<sup>2</sup>, 0.004; 95% CI, −3.551 to 5.818;<i>P</i> = .63). No differences were observed when the analysis examined gray or white matter only or was confined to those achieving target BP. The number of adverse events did not differ between treatment groups, with a mean (SD) of 0.21 (0.65) for the standard group and 0.32 (0.75) for the intensive group (<i>P</i> = .44). <h3>Conclusions and Relevance</h3> Intensive BP lowering did not reduce cerebral perfusion in severe small vessel disease. <h3>Trial Registration</h3> isrctn.org Identifier: ISRCTN37694103
A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins
Authors: Joaquín Letelier, Elisa de la Calle-Mustienes, Joyce Pieretti, Silvia Naranjo, Ignacio Maeso, Tetsuya Nakamura, Juan Pascual-Anaya, Neil H. Shubin, Igor Schneider, Juan Ramón Martinez-Morales, José Luis Gómez-Skarmeta
Journal: Nature Genetics (2018)
ROUTINE EARLY DISCHARGE AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT: A PROPENSITY SCORE ANALYSIS FROM THE PARTNER 2 SAPIEN 3 STUDY
Authors: Chandan M. Devireddy, Vasilis Babaliaros, Robert A. Guyton, James Stewart, Yangbo Liu, Raj Makkar, Michael J. Mack, Brian Whisenant, Stephen Ramee, Paul Teirstein, Thomas McAndrew, Aaron Crowley, Susheel K. Kodali, Suzanne Baron, David Cohen, Martin B. Leon, Vinod H. Thourani
Journal: Journal of the American College of Cardiology (2018)
Bedaquiline and delamanid for the treatment of multidrug-resistant tuberculosis: a multicentre cohort study in Korea
Authors: Cheon Tae Kim, Tae-Ok Kim, Hong-Joon Shin, Young Chun Ko, Yeong Hun Choe, Hak-Ryul Kim, Yong-Soo Kwon
Journal: European Respiratory Journal (2018)

Relatively little is known about the efficacy and safety of the programmatic use of bedaquiline and delamanid in multidrug-resistant tuberculosis (MDR-TB) treatment. This study evaluated 61 patients with MDR-TB treated with bedaquiline (n=39), delamanid (n=11) or both, either sequentially (n=10) or in coadministration (n=1), for &gt;1 month, combined with a World Health Organization-recommended regimen. Of these, 49 (80.3%) were male and 12 (19.7%) were female. The median (interquartile range (IQR)) age was 53 (38.5–61.0) years. 42 (68.9%) patients had fluoroquinolone-resistant MDR-TB and 16 (26.2%) had extensively drug-resistant TB. The median (IQR) duration of treatment with bedaquiline and/or delamanid was 168 (166.5–196.5) days, with 33 (54.1%) receiving linezolid for a median (IQR) of 673 (171–736) days. Of the 55 patients with positive sputum cultures at the start of bedaquiline and/or delamanid treatment, 39 (70.9%) achieved sputum culture conversion within a median of 119 days. Treatment was halted in four patients (6.6%) because of prolonged Fridericia's corrected QT interval. Bedaquiline and delamanid were effective and safe for treating MDR-TB, with initial evidence of sequential administration of these two drugs as a viable treatment strategy for patients when an adequate treatment regimen cannot be constructed.
<i>Helicobacter pylori</i> Therapy for the Prevention of Metachronous Gastric Cancer
Authors: Il Ju Choi, Myeong-Cherl Kook, Young-Il Kim, Soo-Jeong Cho, Jong Yeul Lee, Chan Gyoo Kim, Boram Park, Byung-Ho Nam
Journal: New England Journal of Medicine (2018)

Patients with early gastric cancers that are limited to gastric mucosa or submucosa usually have an advanced loss of mucosal glandular tissue (glandular atrophy) and are at high risk for subsequent (metachronous) development of new gastric cancer. The long-term effects of treatment to eradicate Helicobacter pylori on histologic improvement and the prevention of metachronous gastric cancer remain unclear.