tbuckley/cabot-search huggingface dataset:
Vertebroplasty versus sham procedure for painful acute osteoporotic vertebral compression fractures (VERTOS IV): randomised sham controlled clinical trial
Authors: Cristina E Firanescu, Jolanda de Vries, Paul Lodder, Alexander Venmans, Marinus C Schoemaker, Albert J Smeet, Esther Donga, Job R Juttmann, Caroline A H Klazen, Otto E H Elgersma, Frits H Jansen, Alexander V Tielbeek, Issam Boukrab, Karen Schonenberg, Willem Jan J van Rooij, Joshua A Hirsch, Paul N M Lohle
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To assess whether percutaneous vertebroplasty results in more pain relief than a sham procedure in patients with acute osteoporotic compression fractures of the vertebral body. <h3>Design</h3> Randomised, double blind, sham controlled clinical trial. <h3>Setting</h3> Four community hospitals in the Netherlands, 2011-15. <h3>Participants</h3> 180 participants requiring treatment for acute osteoporotic vertebral compression fractures were randomised to either vertebroplasty (n=91) or a sham procedure (n=89). <h3>Interventions</h3> Participants received local subcutaneous lidocaine (lignocaine) and bupivacaine at each pedicle. The vertebroplasty group also received cementation, which was simulated in the sham procedure group. <h3>Main outcome measures</h3> Main outcome measure was mean reduction in visual analogue scale (VAS) scores at one day, one week, and one, three, six, and 12 months. Clinically significant pain relief was defined as a decrease of 1.5 points in VAS scores from baseline. Secondary outcome measures were the differences between groups for changes in the quality of life for osteoporosis and Roland-Morris disability questionnaire scores during 12 months’ follow-up. <h3>Results</h3> The mean reduction in VAS score was statistically significant in the vertebroplasty and sham procedure groups at all follow-up points after the procedure compared with baseline. The mean difference in VAS scores between groups was 0.20 (95% confidence interval −0.53 to 0.94) at baseline, −0.43 (−1.17 to 0.31) at one day, −0.11 (−0.85 to 0.63) at one week, 0.41 (−0.33 to 1.15) at one month, 0.21 (−0.54 to 0.96) at three months, 0.39 (−0.37 to 1.15) at six months, and 0.45 (−0.37 to 1.24) at 12 months. These changes in VAS scores did not, however, differ statistically significantly between the groups during 12 months’ follow-up. The results for secondary outcomes were not statistically significant. Use of analgesics (non-opioids, weak opioids, strong opioids) decreased statistically significantly in both groups at all time points, with no statistically significant differences between groups. Two adverse events occurred in the vertebroplasty group: one respiratory insufficiency and one vasovagal reaction. <h3>Conclusions</h3> Percutaneous vertebroplasty did not result in statistically significantly greater pain relief than a sham procedure during 12 months’ follow-up among patients with acute osteoporotic vertebral compression fractures. <h3>Trial registration</h3> ClinicalTrials.gov NCT01200277.
TCTAP A-030 Rotational Atherectomy and New-generation Drug-eluting Stent Implantation in De Novo Lesion
Authors: Daisuke Hachinohe, Yoshifumi Kashima, Hidemasa Shitan, Tomohiko Watanabe, Takuro Sugie, Yutaka Tadano, Umihiko Kaneko, Ken Kobayashi, Daitaro Kanno, Morio Enomoto, Tsutomu Fujita
Journal: Journal of the American College of Cardiology (2018)
Excess under-5 female mortality across India: a spatial analysis using 2011 census data
Authors: Christophe Z Guilmoto, Nandita Saikia, Vandana Tamrakar, Jayanta Kumar Bora
Journal: The Lancet Global Health (2018)

Excess female mortality causes half of the missing women (estimated deficit of women in countries with suspiciously low proportion of females in their population) today. Globally, most of these avoidable deaths of women occur during childhood in China and India. We aimed to estimate excess female under-5 mortality rate (U5MR) for India's 35 states and union territories and 640 districts.Using the summary birth history method (or Brass method), we derived district-level estimates of U5MR by sex from 2011 census data. We used data from 46 countries with no evidence of gender bias for mortality to estimate the effects and intensity of excess female mortality at district level. We used a detailed spatial and statistical analysis to highlight the correlates of excess mortality at district level.Excess female U5MR was 18·5 per 1000 livebirths (95% CI 13·1-22·6) in India 2000-2005, which corresponds to an estimated 239 000 excess deaths (169 000-293 000) per year. More than 90% of districts had excess female mortality, but the four largest states in northern India (Uttar Pradesh, Bihar, Rajasthan, and Madhya Pradesh) accounted for two-thirds of India's total number. Low economic development, gender inequity, and high fertility were the main predictors of excess female mortality. Spatial analysis confirmed the strong spatial clustering of postnatal discrimination against girls in India.The considerable effect of gender bias on mortality in India highlights the need for more proactive engagement with the issue of postnatal sex discrimination and a focus on the northern districts. Notably, these regions are not the same as those most affected by skewed sex ratio at birth.None.
Thousands of junior doctors face anxious wait after job offer debacle
Authors: Deborah Cohen
Journal: BMJ (2018)

As many as 1500 junior doctors face uncertainty about their future after “human error” at the Royal College of Physicians (RCP) meant that some ST3 candidates were wrongly ranked and may have received incorrect job offers.

Last month doctors throughout England, Scotland, Wales, and Northern Ireland who applied to the nationally coordinated ST3 recruitment process were notified of their score, which indicates their likelihood of getting a job in one of 24 medical specialties.

However, on Thursday 3 May the RCP discovered that a considerable number of candidates had been credited with the wrong score because of an error in transferring data from one computer program to another. Affected candidates were notified the next …
Primary Sclerosing Cholangitis Risk Estimate Tool (PREsTo) Predicts Outcomes of the Disease: A Derivation and Validation Study Using Machine Learning
Authors: John E. Eaton, Mette Vesterhus, Bryan M. McCauley, Elizabeth J. Atkinson, Erik M. Schlicht, Brian D. Juran, Andrea A. Gossard, Nicholas F. LaRusso, Gregory J. Gores, Tom H. Karlsen, Konstantinos N. Lazaridis
Journal: Hepatology (2018)

Improved methods are needed to risk stratify and predict outcomes in patients with primary sclerosing cholangitis (PSC). Therefore, we sought to derive and validate a prediction model and compare its performance to existing surrogate markers. The model was derived using 509 subjects from a multicenter North American cohort and validated in an international multicenter cohort (n = 278). Gradient boosting, a machine‐based learning technique, was used to create the model. The endpoint was hepatic decompensation (ascites, variceal hemorrhage, or encephalopathy). Subjects with advanced PSC or cholangiocarcinoma (CCA) at baseline were excluded. The PSC risk estimate tool (PREsTo) consists of nine variables: bilirubin, albumin, serum alkaline phosphatase (SAP) times the upper limit of normal (ULN), platelets, aspartate aminotransferase (AST), hemoglobin, sodium, patient age, and number of years since PSC was diagnosed. Validation in an independent cohort confirms that PREsTo accurately predicts decompensation (C‐statistic, 0.90; 95% confidence interval [CI], 0.84‐0.95) and performed well compared to Model for End‐Stage Liver Disease (MELD) score (C‐statistic, 0.72; 95% CI, 0.57‐0.84), Mayo PSC risk score (C‐statistic, 0.85; 95% CI, 0.77‐0.92), and SAP &lt;1.5 × ULN (C‐statistic, 0.65; 95% CI, 0.55‐0.73). PREsTo continued to be accurate among individuals with a bilirubin &lt;2.0 mg/dL (C‐statistic, 0.90; 95% CI, 0.82‐0.96) and when the score was reapplied at a later course in the disease (C‐statistic, 0.82; 95% CI, 0.64‐0.95). Conclusion: PREsTo accurately predicts hepatic decompensation (HD) in PSC and exceeds the performance among other widely available, noninvasive prognostic scoring systems.
Mixed Epithelial and Stromal Tumor of the Kidney Mimicking Malignancy on 18F-FDG PET/CT in a Patient With Breast Cancer
Authors: Chongjiao Li, Yueli Tian, Meijuan Shen, Bing Wen, Yong He
Journal: Clinical Nuclear Medicine (2018)

Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare renal tumor composed of solid and cystic components. Mixed epithelial and stromal tumor of the kidney has no pathognomonic imaging feature. It is difficult to distinguish MESTK from other cystic renal neoplasms using current radiological methods. We report a rare case of MESTK that was diagnosed in a 46-year-old woman with breast cancer. F-FDG PET/CT and contrast-enhanced CT features of MESTK are presented, which could potentially provide useful information in the differential diagnoses of cystic renal neoplasms.
Deception by researchers is necessary and not necessarily evil
Authors: David J. Weiss
Journal: Behavioral and Brain Sciences (2001)

Despite claims of pure pragmatism, Hertwig and Ortmann's negative perspective on deception suggests a selfish psychologist willing to sacrifice the reputation of the discipline in order to expedite the research. Although questions that appear to have correct answers may be investigated with complete openness, research that delves into personal secrets often requires deception as a tool to counter self-presentation bias.
Drugs should be legalised, regulated, and taxed
Authors: Fiona Godlee
Journal: BMJ (2018)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Drugs should be legalised, regulated, and taxed Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Pneumonic and non-pneumonic exacerbations in bronchiectasis: Clinical and microbiological differences
Authors: Eva Polverino, Edmundo Rosales-Mayor, Mariana Benegas, Rosario Menendez, Victoria Alcaraz-Serrano, Emilio Ansotegui, Beatriz Montull, Rosa María Girón, Carolina Cisneros, Montserrat Vendrell, Gerard Muñoz, María Angeles Marcos, Marcelo Sanchez, Antoni Torres
Journal: Journal of Infection (2018)
Monocyte Chemoattractant Protein‐Induced Protein 1 Targets Hypoxia‐Inducible Factor 1α to Protect Against Hepatic Ischemia/Reperfusion Injury
Authors: Peng Sun, Yue‐Xin Lu, Daqing Cheng, Kuo Zhang, Jilin Zheng, Yupeng Liu, Xiaozhan Wang, Yu‐Feng Yuan, Yi‐Da Tang
Journal: Hepatology (2018)

Sterile inflammation is an essential factor causing hepatic ischemia/reperfusion (I/R) injury. As a critical regulator of inflammation, the role of monocyte chemoattractant protein‐induced protein 1 (MCPIP1) in hepatic I/R injury remains undetermined. In this study, we discovered that MCPIP1 downregulation was associated with hepatic I/R injury in liver transplant patients and a mouse model. Hepatocyte‐specific Mcpip1 gene knockout and transgenic mice demonstrated that MCPIP1 functions to ameliorate liver damage, reduce inflammation, prevent cell death, and promote regeneration. A mechanistic study revealed that MCPIP1 interacted with and maintained hypoxia‐inducible factor 1α (HIF‐1α) expression by deubiquitinating HIF‐1α. Notably, the HIF‐1α inhibitor reversed the protective effect of MCPIP1, whereas the HIF‐1α activator compensated for the detrimental effect of MCPIP1 deficiency. Thus, we identified the MCPIP1–HIF‐1α axis as a critical pathway that may be a good target for intervention in hepatic I/R injury. (H epatology 2018; 00:000‐000).
The anti-inflammatory receptor TREM2 halts the generation of HCC in mice through the inhibition of liver inflammation and hepatocyte proliferative responses
Authors: A. Esparza-Baquer, I. Labiano, O. Sharif, F. Oakley, E. Hijona, R. Jimenez-Aguero, C.O. Rourke, J. Andersen, S. Knapp, D.A. Mann, L. Bujanda, J. Banales, M.J. Perugorria
Journal: Journal of Hepatology (2018)
Dysregulation of sphingolipid metabolism contributes to bortezomib-induced neuropathic pain
Authors: Katherine Stockstill, Timothy M. Doyle, Xisheng Yan, Zhoumou Chen, Kali Janes, Joshua W. Little, Kathryn Braden, Filomena Lauro, Luigino Antonio Giancotti, Caron Mitsue Harada, Ruchi Yadav, Wen Hua Xiao, Jack M. Lionberger, William L. Neumann, Gary J. Bennett, Han-Rong Weng, Sarah Spiegel, Daniela Salvemini
Journal: The Journal of Experimental Medicine (2018)

The development of chemotherapy-induced painful peripheral neuropathy is a major dose-limiting side effect of many chemotherapeutics, including bortezomib, but the mechanisms remain poorly understood. We now report that bortezomib causes the dysregulation of de novo sphingolipid metabolism in the spinal cord dorsal horn to increase the levels of sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) ligands, S1P and dihydro-S1P. Accordingly, genetic and pharmacological disruption of S1PR1 with multiple S1PR1 antagonists, including FTY720, blocked and reversed neuropathic pain. Mice with astrocyte-specific alterations of S1pr1 did not develop neuropathic pain and lost their ability to respond to S1PR1 inhibition, strongly implicating astrocytes as a primary cellular substrate for S1PR1 activity. At the molecular level, S1PR1 engaged astrocyte-driven neuroinflammation and altered glutamatergic homeostasis, processes blocked by S1PR1 antagonism. Our findings establish S1PR1 as a target for therapeutic intervention and provide insight into cellular and molecular pathways. As FTY720 also shows promising anticancer potential and is FDA approved, rapid clinical translation of our findings is anticipated.
BLT1 in dendritic cells promotes Th1/Th17 differentiation and its deficiency ameliorates TNBS-induced colitis
Authors: Jinfeng Zhou, Weiming Lai, Wanjie Yang, Juping Pan, Hu Shen, Yingying Cai, Cuixia Yang, Ningjia Ma, Yue Zhang, Ru Zhang, Xin Xie, Zhongjun Dong, Yuan Gao, Changsheng Du
Journal: Cellular and Molecular Immunology (2018)
Proteomic analysis of hepatitis B virus cccDNA-specific associated proteins identifies crucial regulators of viral transcription and RNA processing
Authors: B. Testoni, D. Avila, J. Walther, J.D. Zhang, A.J. Muelle-Breckenridge, F. Chapus, M. Locatelli, H. Meistermann, S. Maadadi, A. Diederichs, J. Fresquet, C. Bieniossek, J. Young, S. Luangsay, F. Zoulim
Journal: Journal of Hepatology (2018)
A phase II trial of gemcitabine (G), cisplatin (C), and nab-paclitaxel (N) in advanced biliary tract cancers (aBTCs).
Authors: Rachna T. Shroff, Mitesh J. Borad, Lianchun Xiao, Ahmed Omar Kaseb, Gauri R. Varadhachary, Robert A. Wolff, Kanwal Pratap Singh Raghav, Michiko Iwasaki, Peter Masci, Ramesh K. Ramanathan, Daniel H. Ahn, Tanios S. Bekaii-Saab, Milind M. Javle
Journal: Journal of Clinical Oncology (2017)

4018 Background: BTCs are often diagnosed at an advanced stage and have a poor prognosis. The standard therapy for aBTCs is the combination of GC. However, the median overall survival (mOS) is dismal at 11.7 months (mos) with a median progression free survival (mPFS) of 8 mos. Methods: A single arm, phase II study was conducted at MD Anderson and Mayo Clinic Arizona. Patients (pts) with aBTC were treated at initial dose level of G/C/N (in mg/m 2 ) at 1000/25/125 (n = 27) which was reduced to lower doses due to grade 3/4 hematological (heme) toxicity (tox) - G/C/N: 800/25/100 (n = 33). Cycles were q21 days with restaging q3 cycles until progression. PFS was the primary endpoint (endpt). Using a Bayesian hypothesis test-based design, we assumed mPFS of 8 mos under the null hypothesis (H0), 10 mos under the alternative (H1). Secondary endpts included mOS, RECIST v1.1 response rate (RR), safety and CA19-9 response. Results: 60 pts were enrolled with data on 51 available as of the time of this abstract (age: median 60 yrs [range 31-77], ECOG PS 0/1 (17/34), M/F (30/21), intrahepatic cholangiocarcinoma/extrahepatic/gallbladder (32/8/11). Median follow-up was 11.5 mos and median number of treatment (trmt) cycles = 5. Pts at initial dose level had significant grade 3/4 heme tox: neutropenia, febrile neutropenia, anemia, and thrombocytopenia leading to trmt discontinuation in 6/27 pts. After dose reduction to G/C/N (in mg/m 2 ) at 800/25/100, trmt was better tolerated with only 4 pts experiencing grade 4 heme tox. Non-heme tox were grade 3 in 10 pts: nausea/vomiting, diarrhea, thromboembolic event/CVA, hypokalemia, constipation, cystitis, LFT elevations. In the initial 51 pts, mPFS = 11.4 mos (95% CI: 6.1, not reached) and mOS not reached (estimated &gt; 20 mos, 1-year survival rate 66.7%; 95%CI: 65.9-92.2%). 34 pts evaluable for response: disease control rate (PR+CR+SD)-82.3% and RR-32.3%. 3 unresectable cases were operated post trmt with 1 pathologic CR. Conclusions: The combination of GCN was well tolerated at adjusted doses and demonstrates encouraging preliminary efficacy having met its mPFS endpt and a 1-year survival rate higher than historical control. These results merit evaluating GC +/-N in a randomized controlled study. Clinical trial information: NCT02392637.
Survival of syngeneic and allogeneic iPSC–derived neural precursors after spinal grafting in minipigs
Authors: Jan Strnadel, Cassiano Carromeu, Cedric Bardy, Michael Navarro, Oleksandr Platoshyn, Andreas N. Glud, Silvia Marsala, Jozef Kafka, Atsushi Miyanohara, Tomohisa Kato, Takahiro Tadokoro, Michael P. Hefferan, Kota Kamizato, Tetsuya Yoshizumi, Stefan Juhas, Jana Juhasova, Chak-Sum Ho, Taba Kheradmand, PeiXi Chen, Dasa Bohaciakova, Marian Hruska-Plochan, Andrew J. Todd, Shawn P. Driscoll, Thomas D. Glenn, Samuel L. Pfaff, Jiri Klima, Joseph Ciacci, Eric Curtis, Fred H. Gage, Jack Bui, Kazuhiko Yamada, Alysson R. Muotri, Martin Marsala
Journal: Science Translational Medicine (2018)

Syngeneic iPSC–derived neurons survive and mature without immunosuppression after grafting into the spinal cord of adult pigs.
Plasma VEGF-A (pVEGF-A) level in efficacy analysis of metastatic colorectal cancer patients (mCRC) treated with mFOLFOX6/XELOX plus bevacizumab (BV) (WJOG7612GTR).
Authors: Wataru Okamoto, Akitaka Makiyama, Yoshiyuki Yamamoto, Kohei Shitara, Tadamichi Denda, Naoki Izawa, Yasuyuki Nakano, Tomohiro Nishina, Taito Esaki, Hiroki Hara, Yukinori Ozaki, Hiroyuki Okuda, Narikazu Boku, Ichinosuke Hyodo, Kentaro Yamazaki, Shuichi Hironaka, Kazuko Sakai, Takeharu Yamanaka, Kei Muro, Kazuto Nishio
Journal: Journal of Clinical Oncology (2018)

699 Background: Plasma levels of VEGF-A short isoforms (VEGF-A110 and -A121) measured by immunological multiparametric chip technique (IMPACT) were reported to be associated with clinical benefits from bevacizumab (BV) in advanced gastric and pancreatic cancer but not in metastatic colorectal cancer (mCRC). Negative results in mCRC studies might be caused by different sample handling: citrate instead of EDTA and repetition of freeze/thaw. Methods: Blood samples were collected in EDTA before the first-line treatment with BV+mFOLFOX6 or +XELOX for mCRC. Plasma samples were analyzed at Roche Diagnostics Ltd. (Penzberg, Germany) using IMPACT-2 (Roche proprietary multiplex enzyme-linked immunosorbent assay platform). A median value of pVEGF-A was used as a cut-off point to categorize patients (pts) into the low and high pVEGF-A groups. Progression free survival (PFS) and overall survival (OS) between the low and high pVEGF-A groups were compared, using Cox proportional hazards model. We hypothesized that BV-containing treatment extend shorter PFS of pts with high pVEGF-A to that with low pVEGF-A, and estimated a threshold hazard ratio (HR) between them as below 1.15. Results: Among 102 pts enrolled between January 2014 and April 2015, 100 (53 BV+mFOLFOX6 and 47 BV+XELOX) were eligible. Median PFS was 11.4 months [95% CI, 9.5-13.0] and response rate was 64.6 % [range, 53.3-74.9]. pVEGF-A was measured in 97 pts and the median value was 36.8 pg/ml [range, 6.5- 262.2]. The hazard ratios of PFS and OS between the high and low pVEGF-A groups were 1.23 [95%CI, 0.76-1.97, p = 0.40] and 2.47 [95%CI, 1.14-5.36, p = 0.02], respectively. Conclusions: mCRC pts with high pVEGF-A showed shorter PFS than those with low pVEGF-A beyond the predefined threshold (HR 1.15) in BV-containing chemotherapy, suggesting that pVEGF-A could not be a predictive marker for BV efficacy. Clinical trial information: UMIN000012442.
Adding dasatinib to intensive treatment in core-binding factor acute myeloid leukemia—results of the AMLSG 11-08 trial
Authors: Peter Paschka, Richard F Schlenk, Daniela Weber, Axel Benner, Lars Bullinger, Michael Heuser, Verena I Gaidzik, Felicitas Thol, Mridul Agrawal, Veronica Teleanu, Michael Lübbert, Walter Fiedler, Markus Radsak, Jürgen Krauter, Heinz-A. Horst, Richard Greil, Karin Mayer, Andrea Kündgen, Uwe Martens, Gerhard Heil, Helmut R Salih, Bernd Hertenstein, Carsten Schwänen, Gerald Wulf, Elisabeth Lange, Michael Pfreundschuh, Mark Ringhoffer, Michael Girschikofsky, Thomas Heinicke, Doris Kraemer, Gudrun Göhring, Arnold Ganser, Konstanze Döhner, Hartmut Döhner
Journal: Leukemia (2018)
Therapeutic Benefit of Autophagy Modulation in Pompe Disease
Authors: Jeong-A Lim, Baodong Sun, Rosa Puertollano, Nina Raben
Journal: Molecular Therapy (2018)

The complexity of the pathogenic cascade in lysosomal storage disorders suggests that combination therapy will be needed to target various aspects of pathogenesis. The standard of care for Pompe disease (glycogen storage disease type II), a deficiency of lysosomal acid alpha glucosidase, is enzyme replacement therapy (ERT). Many patients have poor outcomes due to limited efficacy of the drug in clearing muscle glycogen stores. The resistance to therapy is linked to massive autophagic buildup in the diseased muscle. We have explored two strategies to address the problem. Genetic suppression of autophagy in muscle of knockout mice resulted in the removal of autophagic buildup, increase in muscle force, decrease in glycogen level, and near-complete clearance of lysosomal glycogen following ERT. However, this approach leads to accumulation of ubiquitinated proteins, oxidative stress, and exacerbation of muscle atrophy. Another approach involves AAV-mediated TSC knockdown in knockout muscle leading to upregulation of mTOR, inhibition of autophagy, reversal of atrophy, and efficient cellular clearance on ERT. Importantly, this approach reveals the possibility of reversing already established autophagic buildup, rather than preventing its development.