tbuckley/cabot-search huggingface dataset:
Unexplained mortality differences between septic shock trials: a systematic analysis of population characteristics and control-group mortality rates
Authors: Harm-Jan de Grooth, Jonne Postema, Stephan A. Loer, Jean-Jacques Parienti, Heleen M. Oudemans-van Straaten, Armand R. Girbes
Journal: Intensive Care Medicine (2018)

Although the definition of septic shock has been standardized, some variation in mortality rates among clinical trials is expected. Insights into the sources of heterogeneity may influence the design and interpretation of septic shock studies. We set out to identify inclusion criteria and baseline characteristics associated with between-trial differences in control group mortality rates. We conducted a systematic review of RCTs published between 2006 and 2018 that included patients with septic shock. The percentage of variance in control-group mortality attributable to study heterogeneity rather than chance was measured by I2. The association between control-group mortality and population characteristics was estimated using linear mixed models and a recursive partitioning algorithm. Sixty-five septic shock RCTs were included. Overall control-group mortality was 38.6%, with significant heterogeneity (I2 = 93%, P < 0.0001) and a 95% prediction interval of 13.5–71.7%. The mean mortality rate did not differ between trials with different definitions of hypotension, infection or vasopressor or mechanical ventilation inclusion criteria. Population characteristics univariately associated with mortality rates were mean Sequential Organ Failure Assessment score (standardized regression coefficient (β) = 0.57, P = 0.007), mean serum creatinine (β = 0.48, P = 0.007), the proportion of patients on mechanical ventilation (β = 0.61, P < 0.001), and the proportion with vasopressors (β = 0.57, P = 0.002). Combinations of population characteristics selected with a linear model and recursive partitioning explained 41 and 42%, respectively, of the heterogeneity in mortality rates. Among 65 septic shock trials, there was a clinically relevant amount of heterogeneity in control group mortality rates which was explained only partly by differences in inclusion criteria and reported baseline characteristics.
Robotic versus laparoscopic gastrectomy for gastric adenocarcinoma: Propensity matched analysis of the National Cancer Database.
Authors: Sean Ryan, Amy Murphy, Ashley Tameron, Lala Hussain, Annabelle Teng, Erik M. Dunki-Jacobs, David Y Lee
Journal: Journal of Clinical Oncology (2018)

104 Background: The use of robotic technology in gastrointestinal surgical oncology is on the rise. We compared the outcomes of laparoscopic (LG) and robotic gastrectomies (RG) performed for gastric adenocarcinoma (GA) in the National Cancer Database (NCDB). Methods: The NCDB database was queried for patients ≥ 18 years old with stage I-III GA who underwent LG or RG. Propensity matching was performed between the two groups with regards to clinical staging, adjuvant treatment, demographics, and the extent of surgery. Results: A cohort of 1893 (1262-LG, 631-RG) patients was identified in a 2:1 propensity matching. Demographics and co-morbidities were similar between the groups. The clinical staging and the extent of the surgery were well matched. The rate of negative margin as well 30 and 90-day mortality was similar between the two cohorts. Outcomes with respect to readmission and length of stay were also similar (Table 1). Long-term survival was not significantly different between the two cohorts, with a median survival of 49 months for LG cohort and 56.1 months in the RG cohort (p=0.405). Also, lymph node (LN) positivity was similar between the two groups (40.1 % 42.8%, p= 0.278) However, the average number of LN sampled was significantly higher in the RA group compared to the LA group (19.6 vs 17.4, p&lt;0.001). Similarly, the percentage of surgeries in which ≥ 15 LNs were sampled was also greater in the RG group compared to the LG group (63.9% vs 57.6%, p=0.010). Conclusions: Greater number of patients in the RG group achieved NCCN guideline of harvesting ≥ 15 lymph nodes for more accurate staging. RG may allow a greater harvest of lymph nodes without increasing short term adverse outcomes compared to LG. Long term outcomes in this well matched cohort appears comparable for both approaches.
An observational study of neurocognitive function in patients undergoing stereotactic radiosurgery at Velindre Cancer Centre
Authors: James Powell, Najmus Sahar iqbal, Maeve Smyth, Anne Johnson, Michelle Smalley, Richard Wise, Derek Jones, Owen Tilsley, Andrew Bryant, Anthony Millin, David G Lewis, John Staffurth
Journal: Neuro-Oncology (2018)

Radiation treatment for brain metastases has traditionally involved whole brain radiotherapy (WBRT). Technical developments now allow radiotherapy to be targeted precisely to small areas of cancer within the brain using stereotactic radiosurgery (SRS). Combining WBRT and SRS improves survival compared with WBRT alone. WBRT has significant side effects particularly on short and long term memory and even with SRS treatment alone recent studies have demonstrated that around half of patients suffer memory impairment. Certain areas of the brain, such as the hippocampus, are considered particularly sensitive to radiotherapy but the mechanism for memory impairment is unknown. Hypotheses include changes in structure, cerebral blood flow and brain connectivity. Equally, radiotherapy tolerance doses for the hippocampus and other structures within the brain important for memory are not well defined. We have obtained funding and ethical approval to conduct a prospective observational study in collaboration with the Cardiff University Brain Research Imaging Centre (CUBRIC). In this study we aim to recruit 40 patients undergoing SRS treatment over 18 months and we will correlate data from neurocognitive function (NCF) tests with radiation dosimetry to cognitive structures and with detailed MRI scans using latest MRI techniques. Detailed NCF assessments, according to the RANO group recommendations, will be conducted before and after SRS treatment. MRI brain scans using a combination of functional structural, spectroscopic and microstructural MRI scans will be performed before and after SRS. Radiotherapy doses received by brain structures important for memory including the hippocampus, amygdala, prefrontal cortex and limbic system will be calculated and correlated with NCF and MRI assessments. We predict that by correlating this information we will obtain important new insights into radiotherapy effects on memory and on the radiotherapy tolerance doses for these crucial structures when delivering SRS.
Emergence of Monkeypox — West and Central Africa, 1970–2017
Authors: Kara N. Durski, Andrea M. McCollum, Yoshinori Nakazawa, Brett W. Petersen, Mary G. Reynolds, Sylvie Briand, Mamoudou Harouna Djingarey, Victoria Olson, Inger K. Damon, Asheena Khalakdina
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

The recent apparent increase in human monkeypox cases across a wide geographic area, the potential for further spread, and the lack of reliable surveillance have raised the level of concern for this emerging zoonosis. In November 2017, the World Health Organization (WHO), in collaboration with CDC, hosted an informal consultation on monkeypox with researchers, global health partners, ministries of health, and orthopoxvirus experts to review and discuss human monkeypox in African countries where cases have been recently detected and also identify components of surveillance and response that need improvement. Endemic human monkeypox has been reported from more countries in the past decade than during the previous 40 years. Since 2016, confirmed cases of monkeypox have occurred in Central African Republic, Democratic Republic of the Congo, Liberia, Nigeria, Republic of the Congo, and Sierra Leone and in captive chimpanzees in Cameroon. Many countries with endemic monkeypox lack recent experience and specific knowledge about the disease to detect cases, treat patients, and prevent further spread of the virus. Specific improvements in surveillance capacity, laboratory diagnostics, and infection control measures are needed to launch an efficient response. Further, gaps in knowledge about the epidemiology and ecology of the virus need to be addressed to design, recommend, and implement needed prevention and control measures.
Characteristics of Hospitals Earning Savings in the First Year of Mandatory Bundled Payment for Hip and Knee Surgery
Authors: Amol S. Navathe, Joshua M. Liao, Yash Shah, Zoe Lyon, Paula Chatterjee, Dan Polsky, Ezekiel J. Emanuel
Journal: JAMA (2018)

Characteristics of Hospitals Earning Savings in the First Year of Mandatory Bundled Payment for Hip and Knee SurgerySince April 2016, Medicare has bundled payments for hip and knee surgery at 799 hospitals through the Comprehensive Care for Joint Replacement (CJR) program, which combined payments for hospitalization and postdischarge care in the following 90 days into a single benchmark.CJR incentivizes quality and cost containment by providing retrospective bonus payments that increase as hospitals exceed their quality and cost benchmarks.Initially, Medicare required participation from hospitals in 67 urban markets defined by metropolitan statistical areas (MSAs), 1 favoring MSAs with above-average episode spending and adequate procedural volume.However, Medicare recently indicated that most hospitals in 34 of 67 MSAs are required to continue in the Table.Characteristics of Savings Hospitals vs Nonsavings Hospitals in the First Year of Comprehensive Care for Joint Replacement (CJR) Characteristics CJR Savings Hospitals, No. (%) (n = 382) CJR Nonsavings Hospitals, No. (%) (n = 417) P Value No. of beds, mean (SD) 301 (285) 230 (201) <.001 Hospital size a Small (<100 beds) 64 (16.9) 109 (26.6) <.
FACTORS ASSOCIATED WITH IMPAIRED QUALITY OF LIFE AMONG ATRIAL FIBRILLATION PATIENTS IN REAL-WORLD CLINICAL PRACTICE: INSIGHTS FROM THE PROSPECTIVE SPRINT-AF REGISTRY
Authors: Andrew C.T. Ha, Christopher Labos, Mahesh Kajil, Michelle Tsigoulis, Jafna Cox, Paul Dorian, G.B. John Mancini, David Gladstone, Evan Lockwood, Ashfaq Shuaib, William Chan, Narendra Singh, Milan Gupta
Journal: Journal of the American College of Cardiology (2018)
Further Investigation of the Role of <i>ACYP2</i> and <i>WFS1</i> Pharmacogenomic Variants in the Development of Cisplatin-Induced Ototoxicity in Testicular Cancer Patients
Authors: Britt I. Drögemöller, Beth Brooks, Carol Critchley, José G. Monzon, Galen E.B. Wright, Geoffrey Liu, Daniel J. Renouf, Christian K. Kollmannsberger, Philippe L. Bedard, Michael R. Hayden, Karen A. Gelmon, Bruce C. Carleton, Colin J.D. Ross
Journal: Clinical Cancer Research (2018)

Purpose: Adverse drug reactions such as ototoxicity, which occurs in approximately one-fifth of adult patients who receive cisplatin treatment, can incur large socioeconomic burdens on patients with testicular cancer who develop this cancer during early adulthood. Recent genome-wide association studies have identified genetic variants in ACYP2 and WFS1 that are associated with cisplatin-induced ototoxicity. We sought to explore the role of these genetic susceptibility factors to cisplatin-induced ototoxicity in patients with testicular cancer.Experimental Design: Extensive clinical and demographic data were collected for 229 patients with testicular cancer treated with cisplatin. Patients were genotyped for two variants, ACYP2 rs1872328 and WFS1 rs62283056, that have previously been associated with hearing loss in cisplatin-treated patients. Analyses were performed to investigate the association of these variants with ototoxicity in this cohort of adult patients with testicular cancer.Results: Pharmacogenomic analyses revealed that ACYP2 rs1872328 was significantly associated with cisplatin-induced ototoxicity [P = 2.83 × 10-3, OR (95% CI):14.7 (2.6-84.2)]. WFS1 rs62283056 was not significantly associated with ototoxicity caused by cisplatin (P = 0.39); however, this variant was associated with hearing loss attributable to any cause [P = 5.67 × 10-3, OR (95% CI): 3.2 (1.4-7.7)].Conclusions: This study has provided the first evidence for the role of ACYP2 rs1872328 in cisplatin-induced ototoxicity in patients with testicular cancer. These results support the use of this information to guide the development of strategies to prevent cisplatin-induced ototoxicity across cancers. Further, this study has highlighted the importance of phenotypic differences in replication studies and has provided further evidence for the role of WFS1 rs62283056 in susceptibility to hearing loss, which may be worsened by cisplatin treatment. Clin Cancer Res; 24(8); 1866-71. ©2018 AACR.
DEVELOPMENT OF A MULTIPLE BIOMARKER PANEL FOR THE IDENTIFICATION OF SEVERE AORTIC STENOSIS: RESULTS FROM THE CATHETER SAMPLED BLOOD ARCHIVE IN CARDIOVASCULAR DISEASES (CASABLANCA) STUDY
Authors: Sammy Elmariah, Cian McCarthy, Nasrien Ibrahim, Deborah Furman, Renata Mukai, Craig Magaret, Rhonda Rhyne, Grady Barnes, Roland Van Kimmenade, James Januzzi
Journal: Journal of the American College of Cardiology (2018)
Effects of Cadmium Exposure on DNA Methylation at Imprinting Control Regions and Genome-Wide in Mothers and Newborn Children
Authors: Michael Cowley, David A. Skaar, Dereje D. Jima, Rachel L. Maguire, Kathleen M. Hudson, Sarah S. Park, Patricia Sorrow, Cathrine Hoyo
Journal: Environmental Health Perspectives (2018)

Imprinted genes are defined by their preferential expression from one of the two parental alleles. This unique mode of gene expression is dependent on allele-specific DNA methylation profiles established at regulatory sequences called imprinting control regions (ICRs). These loci have been used as biosensors to study how environmental exposures affect methylation and transcription. However, a critical unanswered question is whether they are more, less, or equally sensitive to environmental stressors as the rest of the genome.Using cadmium exposure in humans as a model, we aimed to determine the relative sensitivity of ICRs to perturbation of methylation compared to similar, nonimprinted loci in the genome.We assayed DNA methylation genome-wide using bisulfite sequencing of 19 newborn cord blood and 20 maternal blood samples selected on the basis of maternal blood cadmium levels. Differentially methylated regions (DMRs) associated with cadmium exposure were identified.In newborn cord blood and maternal blood, 641 and 1,945 cadmium-associated DMRs were identified, respectively. DMRs were more common at the 15 maternally methylated ICRs than at similar nonimprinted loci in newborn cord blood (p=5.64×10-8) and maternal blood (p=6.22×10-14), suggesting a higher sensitivity for ICRs to cadmium. Genome-wide, Enrichr analysis indicated that the top three functional categories for genes that overlapped DMRs in maternal blood were body mass index (BMI) (p=2.0×10-5), blood pressure (p=3.8×10-5), and body weight (p=0.0014). In newborn cord blood, the top three functional categories were BMI, atrial fibrillation, and hypertension, although associations were not significant after correction for multiple testing (p=0.098). These findings suggest that epigenetic changes may contribute to the etiology of cadmium-associated diseases.We analyzed cord blood and maternal blood DNA methylation profiles genome-wide at nucleotide resolution in individuals selected for high and low blood cadmium levels in the first trimester. Our findings suggest that ICRs may be hot spots for perturbation by cadmium, motivating further study of these loci to investigate potential mechanisms of cadmium action. https://doi.org/10.1289/EHP2085.
ECHOCARDIOGRAPHIC ASSESSMENT OF LEFT VENTRICULAR OUTFLOW TRACT AFTER TRANSCATHETER MITRAL VALVE REPLACEMENT
Authors: Atsushi Hayashi, Jun Yoshida, Satoshi Yamaguchi, Takafumi Nagaura, Tetsuo Kamiyama, Florian Rader, Sabah Skaf, Moody Makar, Tarun Chakravarty, Saibal Kar, Raj Makkar, Robert Siegel, Takahiro Shiota
Journal: Journal of the American College of Cardiology (2018)
Doctors’ sleep loss makes no difference to patient outcomes, researchers find
Authors: Matthew Limb
Journal: BMJ (2015)

Doctors’ loss of sleep due to night work does not lead to any statistically significant difference in clinical outcomes the next day, a Canadian study has found.

But the effect of “profound” sleep loss may warrant further analysis, and doctors should still critically assess the effects of fatigue on performance, the researchers behind the study said.1

A team from Ontario looked at the outcomes of 38 978 patients who had one of 12 scheduled elective procedures on a weekday between 2007 and 2011. Patients were treated by 1448 different physicians at 147 academic and community hospitals.

Half of the 38 978 patients were treated by a physician who had performed surgery the previous night between midnight and 7 am. The other half were assigned to a control group if their treating …
GPs might take back out of hours care if funded and not forced, says BMA
Authors: Caroline White
Journal: BMJ (2013)

GPs want to be more involved in the provision of out of hours care—as long as they are not forced to take back personal responsibility for these services against their will and as long as adequate funding is made available, the BMA has said.

Ultimately it may be worth allowing clinical commissioning groups to become both commissioners and providers of these services, the BMA’s General Practitioners Committee has said in a position paper on the issue (http://bit.ly/17dsDu0).1

The paper, which draws on a round table discussion with doctors’ leaders and patients’ representatives held earlier this month, outlines ways to improve the quality of current provision in an overstretched system.

The paper points out that, contrary to …
Human Elongation Factor 4 Regulates Cancer Bioenergetics by Acting as a Mitochondrial Translation Switch
Authors: Ping Zhu, Yongzhang Liu, Fenglin Zhang, Xiufeng Bai, Zilei Chen, Fugen Shangguan, Bo Zhang, Lingyun Zhang, Qianqian Chen, Deyao Xie, Linhua Lan, Xiangdong Xue, Xing-Jie Liang, Bin Lu, Taotao Wei, Yan Qin
Journal: Cancer Research (2018)

Mitochondria regulate cellular bioenergetics and redox states and influence multiple signaling pathways required for tumorigenesis. In this study, we determined that the mitochondrial translation elongation factor 4 (EF4) is a critical component of tumor progression. EF4 was ubiquitous in human tissues with localization to the mitochondria (mtEF4) and performed quality control on respiratory chain biogenesis. Knockout of mtEF4 induced respiratory chain complex defects and apoptosis, while its overexpression stimulated cancer development. In multiple cancers, expression of mtEF4 was increased in patient tumor tissues. These findings reveal that mtEF4 expression may promote tumorigenesis via an imbalance in the regulation of mitochondrial activities and subsequent variation of cellular redox. Thus, dysregulated mitochondrial translation may play a vital role in the etiology and development of diverse human cancers.Significance: Dysregulated mitochondrial translation drives tumor development and progression. Cancer Res; 78(11); 2813-24. ©2018 AACR.
Structures of respiratory syncytial virus G antigen bound to broadly neutralizing antibodies
Authors: Stanislav O. Fedechkin, Natasha L. George, Jacob T. Wolff, Lawrence M. Kauvar, Rebecca M. DuBois
Journal: Science Immunology (2018)

This work describes two conformational epitopes on a conserved domain of the RSV G glycoprotein that activates human CX3CR1.
Consultant trainers could face increased workload under junior contract
Authors: Abi Rimmer
Journal: BMJ (2016)

Consultants who supervise trainees could see an increase in their workload under the proposed new contract for junior doctors in England, doctors have warned.

Under the proposed new terms and conditions for junior doctors, educational supervisors, who oversee the education of trainees, will be required to agree a personalised work schedule with their trainees and regularly discuss their progress.1

In changes to the way that junior doctors’ hours are monitored, educational supervisors will also be required to process exception reports submitted by trainees who have worked too many hours, and discuss what action is required.

Nirmal Kumar, director of medical education at Wrightington, Wigan and Leigh NHS Foundation Trust, said that the …
NanoVelcro CTC purification systems for expressional analysis of circulating tumor cells from prostate cancer patients.
Authors: Yu Jen Jan, Jie-Fu Chen, Sungyong You, Nu Yao, Shirley Cheng, Michael Freeman, Hsian-Rong Tseng, Edwin M. Posadas
Journal: Journal of Clinical Oncology (2018)

295 Background: Circulating tumor cells (CTCs) are blood borne tumor cells shed from all present disease sites, including primary and metastatic tumors. Researchers have been exploring the use of CTCs to identify important transcriptomic features such as androgen receptor splicing variants in prostate cancer (PCa). Newer transcriptomic profiles such as the prostate cancer classification system (PCS) have been developed that may be useful clinically. Over the past decade, we have been developing the NanoVelcro CTC purification system which includes different stimuli-responsive strategies to capture and release viable CTCs with high efficiency and preserve intact RNA. The purified CTCs can then be subjected to transcriptomic analysis such as qPCR, ddPCR and NanoString’s nCounter system. In this study, we benchmarked the efficiency of these platforms for purification of CTCs from blood specimens and the feasibility for detection of PCa-related RNA signatures from purified CTCs. Methods: NanoVelcro CTC purification system is combined with qPCR and ddPCR platform to detect PCa-specific RNA targets in purified CTCs from patients' blood samples. We also developed a modified PCS panel of 30 genes adapted to the nCounter platform and tested purified CTCs from PCa patient blood samples and performed differential expression analysis for PCa disease profiling. Results: PCa-related RNA signals were detected in 16/17 CTC(+) PCa patients, including 3 of 4 non-metastatic patients. We also tested the gene expressions of the modified PCS panel using 48 patient blood samples. Upon performing clustering of samples based on the RNA signatures, we found the differential expression of CTC-target genes grouped patients in a manner which strongly related to drug response and clinical status. Conclusions: We have shown the capability of purifying CTCs with high efficiency using our system, while retaining cell viability and molecular integrity, allowing for detection of PCa-specific RNA signatures from CTCs. Our non-invasive, blood-based assay will be useful for detecting and continuous monitoring molecular alterations related to disease evolvement, addressing an unmet need for PCa clinical care.