tbuckley/cabot-search huggingface dataset:
Abstract 19726: Circulating Metabolites Predict Acute Kidney Injury After Transcatheter Aortic Valve Replacement
Authors: Sammy Elmariah, Brian R Lindman, Jordan E Morningstar, Vaiibhav Patel, Deborah Furman, Laurie A Farrell, Xu Shi, Eugene P Rhee, Robert E Gerszten
Journal: Circulation (2016)

Introduction:  Acute kidney injury (AKI) occurs commonly after transcatheter aortic valve replacement (TAVR) and is associated with increased perioperative morbidity and mortality. Previously, we identified circulating metabolites associated with renal function and predictive of incident chronic kidney disease (CKD).   Hypothesis:  We hypothesize that these previously identified metabolites will predict AKI after TAVR.   Methods:  We performed liquid chromatography-mass spectrometry-based metabolite profiling on plasma obtained from patients prior to TAVR. AKI was defined using the Valve Academic Research Consortium-2 criteria. Twelve metabolites that reflect renal function were chosen  a prior  for this analysis.   Results:  Of 304 patients (51% female, mean age 82±9 yrs), 38 (13%) developed AKI after TAVR. Patients who developed AKI had a higher baseline creatinine and prevalence of coronary disease and atrial fibrillation (P≤0.01 for all), but similar glomerular filtration rate (GFR; P=0.20). Among the 12 metabolites of interest, 11 significantly correlated with baseline GFR and were differentially detected in those with and without CKD. Before and after adjustment for GFR, age, sex, and diabetes, baseline levels of kynurenic acid, xanthosine, and trimethylamine-N-oxide (TMNO) were predictive of AKI (Table). A metabolic multimarker score based on these 3 circulating metabolites was predictive of AKI (odds ratio of 3 rd  vs. 1 st  tertile: 3.58, 95% CI 1.52-8.44, P=0.002). Incident AKI was 7.5%, 10.7%, and 22.5%, respectively, for increasing tertiles of the multimarker score (P=0.006).   Conclusions:  In elderly patients undergoing TAVR for aortic stenosis, circulating metabolites identify those at highest risk of AKI. Given the serious adverse consequences of AKI, strategies to prevent AKI may be particularly important to test and implement in this high-risk sub-group of patients.
UK is a less attractive place to work, GMC warns, as reliance on overseas doctors increases
Authors: Abi Rimmer
Journal: BMJ (2017)

Some specialties have increased their reliance on doctors from overseas, a report by the General Medical Council has said.

However, it warned that the UK risks becoming a less attractive place for overseas doctors to work, with 6000 fewer non-UK graduates on its register in 2017 compared with six years ago.

These were two of four warning signs that stood out in 2017, said the GMC in its State of Medical Education and Practice report, published on 19 December.1

The report said that emergency medicine, general medicine, and paediatrics had all seen increases of more than 20% in the number of non-UK qualified doctors working in the specialty between 2012 and 2017. These increases were mainly …
Self-Expanding Transcatheter Aortic Valve System for Symptomatic High-Risk Patients With Severe Aortic Stenosis
Authors: Hermann Reichenspurner, Andreas Schaefer, Ulrich Schäfer, Didier Tchétché, Axel Linke, Mark S. Spence, Lars Søndergaard, Hervé LeBreton, Gerhard Schymik, Mohamed Abdel-Wahab, Jonathon Leipsic, Darren L. Walters, Stephen Worthley, Markus Kasel, Stephan Windecker
Journal: Journal of the American College of Cardiology (2017)
Abstract 13485: An Improved Prediction Scoring System To Estimate Survival With Favorable Neurological Outcomes After Out-of-hospital Cardiac Arrest: Evidence From A Nationwide Population-based Cohort Study In Japan
Authors: Akira Funada, Yoshikazu Goto, Tetsuo Maeda, Hayato Tada, Ryota Teramoto, Masaya Shimojima, Kenshi Hayashi, Masakazu Yamagishi
Journal: Circulation (2016)

Introduction: Information on probability of survival with favorable neurological outcomes after out-of-hospital cardiac arrest (OHCA) can be useful for physicians when deciding whether to withhold further resuscitation attempts or terminate on-going resuscitation immediately after patient arrival at the emergency department. Hypothesis: We hypothesized that a prediction scoring system integrated with prehospital variables could identify patients who are unlikely to survive with a favorable neurological outcome. Methods: We analyzed the records of 238,174 adult OHCA patients obtained from a prospectively recorded Japanese national Utstein-style database from 2011 to 2012. The primary endpoint was 1-month survival with favorable neurological outcomes (cerebral performance category [CPC] score, 1 or 2 [CPC 1-2]). We developed a prediction scoring system to estimate 1 month CPC 1-2 after OHCA by using 2011 data (n = 118,631) and validating it by using corresponding 2012 data (n = 119,543). We used multivariate methods to select the best independent predictors of 1 month CPC 1-2 and classified patients as having a very low (&lt;1%), low (1%-5%), average (&gt;5%-15%), or higher than average (&gt;15%) probability of 1 month CPC 1-2. Results: The rate of 1 month CPC 1-2 was 2.1% (n = 4,897). The best performing model was based on 3 prehospital variables: witness status (YES or NO), initial documented shockable rhythm (YES or NO), and age (categorized as 18 to 64, 65 to 74, 75 to 84, or ≥85 years). The C statistic was 0.88 when applied to the validation set. It identified the probability of 1 month CPC 1-2 as very low, low, average, and above average in 70.3%, 23.0%, 3.3%, and 3.5% of patients, respectively (1 month CPC 1-2 in 0.4%, 2.2%, 11.3%, and 26.9% of patients, respectively). Overall, 90% of patients were identified as having a low or very low probability of 1 month CPC 1-2 after OHCA (1 month CPC 1-2 in 0.8% of patients). Conclusions: Our prediction scoring system identifies OHCA patients who are unlikely to benefit from further resuscitation after arrival at the emergency department; this information can aid the decision regarding termination of resuscitation.
Cerebral Abscesses and Osteomyelitis Caused by Fish Bone Impaction on FDG PET/CT Imaging
Authors: Gui-Xiong Zhang, Ting Jiang, Yong-Jiang Mao, Min Yang, Jie-Hua Xu
Journal: Clinical Nuclear Medicine (2017)

Abstract A 50-year-old woman complained postprandial vomiting for 5 days and drowsiness for 3 days. Possible central nervous pathology was suspected clinically. Brain MRI suggested likely brain metastases. For this reason, FDG PET/CT was performed to search the primary malignancy. The images showed abnormal activity not only in the brain, but also in the retropharyngeal region and in the thoracic vertebral body. The lesions were eventually confirmed as infection caused by fish bone impaction that occurred 1 month earlier.
Genomic perturbations reveal distinct regulatory networks in intrahepatic cholangiocarcinoma
Authors: Chirag Nepal, Colm J. O'Rourke, Douglas V.N.P. Oliveira, Andrzej Taranta, Steven Shema, Prson Gautam, Julien Calderaro, Andrew Barbour, Chiara Raggi, Krister Wennerberg, Xin W. Wang, Anja Lautem, Lewis R. Roberts, Jesper B. Andersen
Journal: Hepatology (2017)

Intrahepatic cholangiocarcinoma remains a highly heterogeneous malignancy that has eluded effective patient stratification to date. The extent to which such heterogeneity can be influenced by individual driver mutations remains to be evaluated. Here, we analyzed genomic (whole-exome sequencing, targeted exome sequencing) and epigenomic data from 496 patients and used the three most recurrently mutated genes to stratify patients (IDH, KRAS, TP53, "undetermined"). Using this molecular dissection approach, each subgroup was determined to possess unique mutational signature preferences, comutation profiles, and enriched pathways. High-throughput drug repositioning in seven patient-matched cell lines, chosen to reflect the genetic alterations specific for each patient group, confirmed in silico predictions of subgroup-specific vulnerabilities linked to enriched pathways. Intriguingly, patients lacking all three mutations ("undetermined") harbored the most extensive structural alterations, while isocitrate dehydrogenase mutant tumors displayed the most extensive DNA methylome dysregulation, consistent with previous findings.Stratification of intrahepatic cholangiocarcinoma patients based on occurrence of mutations in three classifier genes (IDH, KRAS, TP53) revealed unique oncogenic programs (mutational, structural, epimutational) that influence pharmacologic response in drug repositioning protocols; this genome dissection approach highlights the potential of individual mutations to induce extensive molecular heterogeneity and could facilitate advancement of therapeutic response in this dismal disease. (Hepatology 2018).
A novel role for the macrophage galactose-type lectin receptor in mediating von Willebrand factor clearance
Authors: Soracha E. Ward, Jamie M. O’Sullivan, Clive Drakeford, Sonia Aguila, Christopher N. Jondle, Jyotika Sharma, Padraic G. Fallon, Teresa M. Brophy, Roger J. S. Preston, Paul Smyth, Orla Sheils, Alain Chion, James S. O’Donnell
Journal: Blood (2017)
Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial
Authors: Benoit Guery, Francesco Menichetti, Veli-Jukka Anttila, Nicholas Adomakoh, Jose Maria Aguado, Karen Bisnauthsing, Areti Georgopali, Simon D Goldenberg, Andreas Karas, Gbenga Kazeem, Chris Longshaw, Jose Alejandro Palacios-Fabrega, Oliver A Cornely, Maria J G T Vehreschild
Journal: The Lancet Infectious Diseases (2017)
Histopathological evaluation of liver fibrosis and cirrhosis regression
Authors: Regina C. Lo, Haeryoung Kim
Journal: Clinical and Molecular Hepatology (2017)

The hepatic repair complex in the setting of cirrhosis has received increasing attention, as it implies the regression of cirrhosis, which was traditionally taken to be an irreversible state. In this brief review, the patterns of fibrosis, the existing staging systems for chronic liver disease and the histopathological features of cirrhosis regression are discussed. Keywords: Liver fibrosis; Cirrhosis; Regression; Hepatic repair complex
Advance care planning (ACP) for specialists managing cirrhosis: A focus on patient‐centered care
Authors: Amanda Brisebois, Kathleen P. Ismond, Michelle Carbonneau, Jan Kowalczewski, Puneeta Tandon
Journal: Hepatology (2017)

Advance care planning (ACP) and goals of care designation (GCD) are being integrated into modern health care. In cirrhosis, uptake and adoption of these practices have been limited with physicians citing many perceived barriers and limitations. Recognizing the many tangible benefits of ACP and GCD processes in patients with life‐limiting chronic diseases, the onus is on health practitioners to initiate and direct these conversations with their patients and surrogates. Drawing upon the literature and our experiences in palliative care and cirrhosis, we provide an actionable framework that can be readily implemented into a busy clinical setting by a practitioner. Conversation starters, visual aids, educational resources (for patients and practitioners), and videos of mock physician‐patient scenarios are presented and discussed. Importantly, we have customized each of these tools to meet the unique health care needs of patients with cirrhosis. The inherent flexibility of our approach to ACP discussions and GCD can be further modified to accommodate practitioner preferences. Conclusion: In our clinics, this assemblage of “best practice tools” has been well received by patients and surrogates enabling us to increase the number of outpatients with cirrhosis who have actively contributed to their GCD before acute health events and are supported by well‐informed surrogates. (H epatology 2018;67:2025‐2040).
Inflammatory dermatoses, infections, and drug eruptions are the most common skin conditions in hospitalized cancer patients
Authors: Gregory S. Phillips, Azael Freites-Martinez, Meier Hsu, Anna Skripnik Lucas, Dulce M. Barrios, Kathryn Ciccolini, Michael A. Marchetti, Liang Deng, Patricia L. Myskowski, Erica H. Lee, Alina Markova, Mario E. Lacouture
Journal: Journal of the American Academy of Dermatology (2017)
Dysbiosis-Associated Change in Host Metabolism Generates Lactate to Support Salmonella Growth
Authors: Caroline C. Gillis, Elizabeth R. Hughes, Luisella Spiga, Maria G. Winter, Wenhan Zhu, Tatiane Furtado de Carvalho, Rachael B. Chanin, Cassie L. Behrendt, Lora V. Hooper, Renato L. Santos, Sebastian E. Winter
Journal: Cell Host & Microbe (2017)
Picroside II attenuates fatty acid accumulation in HepG2 cells via modulation of fatty acid uptake and synthesis
Authors: Hiteshi Dhami-Shah, Rama Vaidya, Shobha Udipi, Srividhya Raghavan, Shiny Abhijit, Viswanathan Mohan, Muthuswamy Balasubramanyam, Ashok Vaidya
Journal: Clinical and Molecular Hepatology (2017)

Hepatic steatosis is caused by an imbalance between free fatty acids (FFAs) uptake, utilization, storage, and disposal. Understanding the molecular mechanisms involved in FFAs accumulation and its modulation could drive the development of potential therapies for Nonalcoholic fatty liver disease. The aim of the current study was to explore the effects of picroside II, a phytoactive found in Picrorhiza kurroa, on fatty acid accumulation vis-à-vis silibinin, a known hepatoprotective phytoactive from Silybum marianum.HepG2 cells were loaded with FFAs (oleic acid:palmitic acid/2:1) for 20 hours to mimic hepatic steatosis. The FFAs concentration achieving maximum fat accumulation and minimal cytotoxicity (500 μM) was standardized. HepG2 cells were exposed to the standardized FFAs concentration with and without picroside II pretreatment.Picroside II pretreatment inhibited FFAs-induced lipid accumulation by attenuating the expression of fatty acid transport protein 5, sterol regulatory element binding protein 1 and stearoyl CoA desaturase. Preatreatment with picroside II was also found to decrease the expression of forkhead box protein O1 and phosphoenolpyruvate carboxykinase.These findings suggest that picroside II effectively attenuated fatty acid accumulation by decreasing FFAs uptake and lipogenesis. Picroside II also decreased the expression of gluconeogenic genes.
Subpopulations of dermal skin fibroblasts secrete distinct extracellular matrix: implications for using skin substitutes in the clinic
Authors: M. Ghetti, H. Topouzi, G. Theocharidis, V. Papa, G. Williams, E. Bondioli, G. Cenacchi, J.T. Connelly, C.A. Higgins
Journal: British Journal of Dermatology (2017)

While several commercial dermoepidermal scaffolds can promote wound healing of the skin, the achievement of complete skin regeneration still represents a major challenge. To perform biological characterization of self‐assembled extracellular matrices (ECMs) from three different subpopulations of fibroblasts found in human skin: papillary fibroblasts (Pfi), reticular fibroblasts (Rfi) and dermal papilla fibroblasts (DPfi). Fibroblast subpopulations were cultured with ascorbic acid to promote cell‐assembled matrix production for 10 days. Subsequently, cells were removed and the remaining matrices characterized. Additionally, in another experiment, keratinocytes were seeded on the top of cell‐depleted ECMs to generate epidermal‐only skin constructs. We found that the ECM self‐assembled by Pfi exhibited randomly oriented fibres associated with the highest interfibrillar space, reflecting ECM characteristics that are physiologically present within the papillary dermis. Mass spectrometry followed by validation with immunofluorescence analysis showed that thrombospondin 1 is preferentially expressed within the DPfi‐derived matrix. Moreover, we observed that epidermal constructs grown on DPfi or Pfi matrices exhibited normal basement membrane formation, whereas Rfi matrices were unable to support membrane formation. We argue that inspiration can be taken from these different ECMs, to improve the design of therapeutic biomaterials in skin engineering applications.
Carfilzomib-Associated Cardiovascular Adverse Events
Authors: Adam J. Waxman, Suparna Clasen, Wei-Ting Hwang, Alfred Garfall, Dan T. Vogl, Joseph Carver, Rupal O’Quinn, Adam D. Cohen, Edward A. Stadtmauer, Bonnie Ky, Brendan M. Weiss
Journal: JAMA Oncology (2017)

Cardiovascular adverse events (CVAE) with carfilzomib in patients with multiple myeloma can be potentially life-threatening and remain incompletely characterized. We performed the first systematic review and meta-analysis of carfilzomib-associated CVAE.To determine the incidence of carfilzomib-associated CVAE and to compare the rates of carfilzomib CVAE among different doses and companion therapies.PubMed, EMBASE, Web of Science, and clinicaltrials.gov were queried for the keywords "carfilzomib," "Kyprolis," and "PX-171" through January 1, 2017.Phase 1 to 3 prospective clinical trials of carfilzomib in patients with multiple myeloma with evaluable toxic effects data were eligible for meta-analysis.Data were independently extracted by 2 reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Pooled incidence rates and relative risks (for randomized trials) and 95% confidence intervals were calculated using a random effects model. Subgroup analyses were performed to assess study-level characteristics associated with CVAE.Cardiovascular adverse events were defined as heart failure, hypertension, ischemia, and arrhythmia. All-grade and grades 3 or higher AEs and study characteristics were recorded.A total of 514 studies were assessed for eligibility. Of those, 24 studies were eligible, including a total of 2594 patients with multiple myeloma. All-grade and grades 3 and higher CVAE were seen in 617 (18.1%) and 274 (8.2%), respectively. Phase 2 or 3 studies and carfilzomib doses of 45 mg/m2 or higher were associated with high-grade CVAE. Median age older than 65 years, prior myeloma therapies, and concurrent myeloma therapies were not associated with CVAE. For the 3 randomized clinical trials, the summary relative risk of all-grade and grade 3 or higher CVAE for patients receiving carfilzomib compared with noncarfilzomib-receiving control patients were 1.8 and 2.2, respectively.Carfilzomib was associated with a significant incidence of CVAE, with higher rates seen with higher doses of carfilzomib. Phase 1 studies may be underdetecting CVAE. Future studies are needed to identify patients at high risk for CVAE, develop optimal monitoring strategies, and explore strategies to mitigate these risks.
Metastasized 18F-DCFPyL–Negative Prostatic Adenocarcinoma Without Neuroendocrine Differentiation
Authors: Wouter A.M. Broos, Marielle Kocken, Friso M. van der Zant, Remco J.J. Knol, Maurits Wondergem
Journal: Clinical Nuclear Medicine (2017)

A 76-year-old man with histopathologically proven prostate cancer (initial prostate-specific antigen 110 ng/mL, Gleason 3 + 4 = 7) received F-DCFPyL PET/CT for initial staging. Both the primary tumor and pathologically enlarged pelvic lymph nodes showed no increased F-DCFPyL uptake. Subsequent histopathologic lymph node biopsy revealed prostate cancer metastasis. Prostate-specific membrane antigen tracers, such as F-DCFPyL, are promising radiopharmaceuticals for prostate cancer imaging. False-negative prostate-specific membrane antigen PET/CT findings have been reported earlier for prostate tumors with neuroendocrine differentiation. However, this report presents false-negative F-DCFPyL PET findings of an adenocarcinoma of the prostate without neuroendocrine differentiation.
Incidence of androgenic dermatologic side effects following placement of a levonorgestrel intrauterine device for menorrhagia: A survey-based study
Authors: Jenna Janiga Lullo, Elizabeth Ethington, Ashish Arshanapalli, Jeave Reserva, Angela Jiang, William Adams, Scott Graziano, Rebecca Tung
Journal: Journal of the American Academy of Dermatology (2017)
Chromothripsis in acute myeloid leukemia: biological features and impact on survival
Authors: Maria Chiara Fontana, Giovanni Marconi, Jelena D. Milosevic Feenstra, Eugenio Fonzi, Cristina Papayannidis, Andrea Ghelli Luserna di Rorá, Antonella Padella, Vincenza Solli, Eugenia Franchini, Emanuela Ottaviani, Anna Ferrari, Carmen Baldazzi, Nicoletta Testoni, Ilaria Iacobucci, Simona Soverini, Torsten Haferlach, Viviana Guadagnuolo, Lukas Semerad, Michael Doubek, Michael Steurer, Zdenek Racil, Stefania Paolini, Marco Manfrini, Michele Cavo, Giorgia Simonetti, Robert Kralovics, Giovanni Martinelli
Journal: Leukemia (2018)

Chromothripsis is a one-step genome-shattering catastrophe resulting from disruption of one or few chromosomes in multiple fragments and consequent random rejoining and repair. This study defines incidence of chromothripsis in 395 newly diagnosed adult acute myeloid leukemia (AML) patients from three institutions, its impact on survival and its genomic background. SNP 6.0 or CytoscanHD Array (Affymetrix®) were performed on all samples. We detected chromothripsis with a custom algorithm in 26/395 patients. Patients harboring chromothripsis had higher age (p = 0.002), ELN high risk (HR) (p < 0.001), lower white blood cell (WBC) count (p = 0.040), TP53 loss, and/or mutations (p < 0.001) while FLT3 (p = 0.025), and NPM1 (p = 0.032) mutations were mutually exclusive with chromothripsis. Chromothripsis-positive patients showed a worse overall survival (OS) (p < 0.001) compared with HR patients (p = 0.011) and a poor prognosis in a COX-HR optimal regression model. Chromothripsis presented the hallmarks of chromosome instability [i.e., TP53 alteration, 5q deletion, higher mean of copy number alteration (CNA), complex karyotype, alterations in DNA repair, and cell cycle] and focal deletions on chromosomes 4, 7, 12, 16, and 17. CBA. FISH showed that chromothripsis is associated with marker, derivative, and ring chromosomes. In conclusion, chromothripsis frequently occurs in AML (6.6%) and influences patient prognosis and disease biology.
Recent advances in mass spectrometry-based approaches for proteomics and biologics: Great contribution for developing therapeutic antibodies
Authors: Noriko Iwamoto, Takashi Shimada
Journal: Pharmacology & Therapeutics (2017)

Since the turn of the century, mass spectrometry (MS) technologies have continued to improve dramatically, and advanced strategies that were impossible a decade ago are increasingly becoming available. The basic characteristics behind these advancements are MS resolution, quantitative accuracy, and information science for appropriate data processing. The spectral data from MS contain various types of information. The benefits of improving the resolution of MS data include accurate molecular structural-derived information, and as a result, we can obtain a refined biomolecular structure determination in a sequential and large-scale manner. Moreover, in MS data, not only accurate structural information but also the generated ion amount plays an important rule. This progress has greatly contributed a research field that captures biological events as a system by comprehensively tracing the various changes in biomolecular dynamics. The sequential changes of proteome expression in biological pathways are very essential, and the amounts of the changes often directly become the targets of drug discovery or indicators of clinical efficacy. To take this proteomic approach, it is necessary to separate the individual MS spectra derived from each biomolecule in the complexed biological samples. MS itself is not so infinite to perform the all peak separation, and we should consider improving the methods for sample processing and purification to make them suitable for injection into MS. The above-described characteristics can only be achieved using MS with any analytical instrument. Moreover, MS is expected to be applied and expand into many fields, not only basic life sciences but also forensic medicine, plant sciences, materials, and natural products. In this review, we focus on the technical fundamentals and future aspects of the strategies for accurate structural identification, structure-indicated quantitation, and on the challenges for pharmacokinetics of high-molecular-weight protein biopharmaceuticals.