tbuckley/cabot-search huggingface dataset:
Systemic immune signature of inflammation in metastatic melanoma (MM) patients treated with ipilimumab (IPI) and carboplatin/paclitaxel (CP).
Authors: Wilson H. Miller, Rahima Jamal, Eftihia Cocolakis, Pamela Thebault, Jennifer Elisabeth Friedmann, Shirin Kazemi, Jeanne Dionne, Jean-Francois Cailhier, Stephanie Lepage, Karl Belanger, Jean-Pierre M. Ayoub, HB Le, Caroline Lambert, Jida El Hajjar, Leon Van Kempen, Alan Spatz, Rejean Lapointe
Journal: Journal of Clinical Oncology (2018)

185 Background: Only a subset of MM patients benefit from treatment with IPI. In an effort to increase response and identify predictive immune biomarkers, we combined IPI with CP. We here report a significant correlation between overall survival (OS) and biomarkers of a pre-existing inflammatory state. Methods: 30 patients were treated with C (AUC = 6) and P (175mg/m 2 ) every 3 weeks x 5 and IPI (3mg/kg) every 3 weeks x 4. Blood was collected throughout. OS Kaplan–Meier curves were compared by the log-rank test. Cutoff thresholds defining high or low levels of chemokines, B cell populations and PD-1 + CD8 + T cell populations were established from the mean value of a given variable from all patients. Neutrophil to Lymphocyte Ratio (NLR) and Systemic Immune Inflammation Index defined as Platelet x Neutrophil to Lymphocyte Ratio (SII) were calculated at baseline and tested for association with OS. SII ≥ 1375 and NLR ≥ 5 were considered as high risk groups. Results: Median OS was 16.2 months, with a 3-year OS of 36.7% for all patients. High levels of CCL3 (HR = 2.79, p = 0.0159), CCL4 (HR = 8.36, p &lt; 0.0001) and CXCL8 (HR = 3.52, p = 0.0037) were associated with worse OS. Advanced B cell differentiation before treatment was associated with worse patient outcomes. High levels of early differentiated Bm2 ( &gt; 57%) were strongly associated with better OS: HR = 0.26 p = 0.004 whereas high eBm5+Bm5 ( &gt; 14%) levels were strongly associated with worse OS: HR = 2.65, p = 0.029. Patients with higher proportions of PD-1 + CD8 + T cells in circulation during treatment had poorer OS (HR = 3.84, p = 0.004) at week 10; (HR = 3.53, p = 0.005) at week 13 and (HR = 2.84, p = 0.040) at week 24. High risk SII (HR = 3.30, p = 0.0192) and NLR (HR = 2.367, p = 0.0486) were associated with worse OS. Conclusions: We have identified a significant correlation between pre-existing systemic inflammatory state and a poor response to IPI and CP. Specifically elevated CCL3, CCL4 and CXCL8, baseline B lymphocyte subset skewing, increased CD8 + PD-1 + T lymphocytes, increased NLR and SII were all strongly associated to worse OS. Comprehensive immune monitoring provides evidence for new circulating biomarkers predicting outcome in MM patients treated with IPI and CP. Clinical trial information: NCT01676649.
The Good Mentoring Toolkit for Healthcare
Authors: Peter Harborow
Journal: BMJ (2005)

<h3>Abstract</h3> Genome-scale models of metabolism (GEM) are now used to study how metabolism varies in different physiological conditions or environments. However, the great number of reactions involved in GEM makes it difficult to understand the results obtained in these studies. In order to have a more understandable tool, we develop a reduced metabolic model of central carbon metabolism, C2M2 with 63 reactions, 46 internal metabolites and 3 compartments, taking into account the actual stoichiometry of the reactions, including the stoichiometric role of the cofactors and the irreversibility of some reactions. In order to model OXPHOS functioning, the proton gradient through the inner mitochondrial membrane is represented by two pseudo-metabolites DPH (ΔpH) and DPSI (Δψ). To illustrate the interest of such a reduced model of metabolism in mammalian cell, we used Flux Balance Analysis (FBA), to systematically study all the possible fates of glutamine in central carbon metabolism. Our analysis shows that glutamine can supply carbon sources for cell energy production and can be used as a carbon source to synthesize essential metabolites thus sustaining cell proliferation. We show how C2M2 can also be used to explore the results of more complex metabolic models in comparing our results with those of a medium size model MitoCore.
Temporal Trends in Gender-Affirming Surgery Among Transgender Patients in the United States
Authors: Joseph K. Canner, Omar Harfouch, Lisa M. Kodadek, Danielle Pelaez, Devin Coon, Anaeze C. Offodile, Adil H. Haider, Brandyn D. Lau
Journal: JAMA Surgery (2018)

<h3>Importance</h3> Little is known about the incidence of gender-affirming surgical procedures for transgender patients in the United States. <h3>Objectives</h3> To investigate the incidence and trends over time of gender-affirming surgical procedures and to analyze characteristics and payer status of transgender patients seeking these operations. <h3>Design, Setting, and Participants</h3> In this descriptive observational study from 2000 to 2014, data were analyzed from the National Inpatient Sample, a representative pool of inpatient visits across the United States. The initial analyses were done from June to August 2015. Patients of interest were identified by<i>International Classification of Diseases</i>,<i>Ninth Revision</i>, diagnosis codes for transsexualism or gender identity disorder. Subanalysis focused on patients with procedure codes for surgery related to gender affirmation. <h3>Main Outcomes and Measures</h3> Demographics, health insurance plan, and type of surgery for patients who sought gender-affirming surgery were compared between 2000-2005 and 2006-2011, as well as annually from 2012 to 2014. <h3>Results</h3> This study included 37 827 encounters (median [interquartile range] patient age, 38 [26-49] years) identified by a diagnosis code of transsexualism or gender identity disorder. Of all encounters, 4118 (10.9%) involved gender-affirming surgery. The incidence of genital surgery increased over time: in 2000-2005, 72.0% of patients who underwent gender-affirming procedures had genital surgery; in 2006-2011, 83.9% of patients who underwent gender-affirming procedures had genital surgery. Most patients (2319 of 4118 [56.3%]) undergoing these procedures were not covered by any health insurance plan. The number of patients seeking these procedures who were covered by Medicare or Medicaid increased by 3-fold in 2014 (to 70) compared with 2012-2013 (from 25). No patients who underwent inpatient gender-affirming surgery died in the hospital. <h3>Conclusions and Relevance</h3> Most transgender patients in this national sample undergoing inpatient gender-affirming surgery were classified as self-pay; however, an increasing number of transgender patients are being covered by private insurance, Medicare, or Medicaid. As coverage for these procedures increases, likely so will demand for qualified surgeons to perform them.
The influence of biliary drainage in patients with advanced pancreatic cancer receiving FOLFIRINOX.
Authors: Makoto Ueno, Takeharu Yamanaka, Takashi Ogura, Atushi Yamaguchi, Nobumasa Mizuno, Masato Ozaka, Hideki Ueno, Kazuhiro Uesugi, Noritoshi Kobayashi, Hideyuki Hayashi, Kentaro Sudo, Naohiro Okano, Yosuke Horita, Keiko Kamei, Takafumi Hosokawa, Toshiyuki Henmi, Marina Kobayashi, Akiko Todaka, Akira Fukutomi
Journal: Journal of Clinical Oncology (2018)

378 Background: FOLFIRINOX (FFX) is a standard of care for patients (pts) with advanced pancreatic cancer (APC). In the original FFX report by Conroy (NEJM, 2011), pts with a biliary drainage were limited and the occurrence of cholangitis was not reported. In practice, however, we experience that a certain fraction of APC pts needs a biliary drainage and some of them have an elevated risk of cholangitis or febrile neutropenia (FN) during the course of FFX. We evaluated the influence of biliary drainage on the efficacy and safety of FFX. Methods: We used individual data from nationwide survey of FFX (JASPAC06). The JASPAC06 was a prospective registry of pts with FFX treated in clinical practice and enrolled 399 pts between December 2013 and November 2014 from 27 centers in Japan. We evaluated the associations of OS and PFS, as well as the frequencies of cholangitis and FN, with the use of biliary drainage. We excluded resected cases because an operative method with choledochojejunostomy was unknown. Results: Of 399 pts in the JASPAC06, 319 were eligible for this analysis and 80 resected cases were excluded. The use of biliary drainage was seen in 28% of pts (mainly bile duct stent inserted); primary dose reduction (modified FFX), 67%; previously untreated tumor, 77%; distant metastases, 76%; pancreas head, 47%. The main results are shown in the table. In summary, cholangitis was more frequent in pts with biliary drainage. Grade 3 or higher FN as well as CRP elevation was observed more frequently in pts with biliary drainage. There was no difference in PFS (median PFS, 7.3 vs. 6.5 mo; logrank, p=0.24) and OS (median OS, 12.3 vs. 12.2 mo; p=0.86) between the two groups. Conclusions: Our observation that the frequency of FN and CRP elevation was significantly higher in pts with biliary drainage indicates a higher risk of infection during the FFX treatment by using biliary drainage.[Table: see text]
GPs oppose CQC plans for “simplistic” rating system for general practice
Authors: Abi Rimmer
Journal: BMJ (2014)

GPs have opposed plans by the Care Quality Commission (CQC) to introduce what they say is a “simplistic rating system” for general practice.

Delegates at the BMA’s local medical committee (LMC) conference in York voted in favour of a motion that “deplores CQC’s plans for a simplistic rating system for practices.” The motion called for help and funding for practices that had problems identified by the CQC. It demanded that “the CQC takes into account what is deliverable and attainable in making their report,” that the …
EFFECTS OF MINIMIZING VENTRICULAR PACING ON THE INCIDENCE OF ATRIAL FIBRILLATION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Ishan Lakhani, Mengqi Gong, Cheuk Wai Wong, Adrian Baranchuk, Konstantinos Letsas, Tong Liu, Gary Tse
Journal: Journal of the American College of Cardiology (2018)
Carcinomas of the renal medulla: A comprehensive genomic profiling (CGP) study.
Authors: Gennady Bratslavsky, Joseph M Jacob, Oleg Shapiro, Julia Andrea Elvin, Jo-Anne Vergilio, James Suh, Shakti Ramkissoon, Siraj Mahamed Ali, Alexa Betzig Schrock, Vincent A. Miller, Philip J. Stephens, Laurie M. Gay, Dimitra Bourboulia, Mehdi Mollapour, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2018)

640 Background: Collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) represent rare tumors that arise in the renal medulla are therapy resistant tumors that progress rapidly. Methods: DNA was extracted from 40 microns of FFPE specimen from refractory CDC (46 cases) and RMC (24 cases). CGPwas performed using a hybrid-capture, adaptor ligation based next generation sequencing assayto a mean coverage depth of &gt; 800X. Tumor mutational burden (TMB) was calculated from a minimum of 1.11 Mb of sequenced DNA as previously described and reported as mutations/Mb. Microsatellite instability status (MSI) was determined on 114 loci. Results: All CDC patients were older and more frequently male (Table). Sickle cell trait was identified in both CDC and RMC, but far more frequently associated with RMC. All (100%) of CDC and RMC were clinically advanced Stage III and IV tumors with the primary tumor used for CGP in 70% of cases and a metastasis biopsy was sequenced in 30%. All (100%) CDC and RMC were intermediate (Grade 3) or high grade (Grade 4). In both tumor types, the GA/tumor was relatively low and there were no (0%) VHL GA. SMARCB1 GA were significantly more frequent in RMC than CDC but common in both tumors. Targeted therapies for kinase ( EGFR, RET) and MTOR ( NF2, TSC2) pathways were more frequent in CDC than RMC. At 1.8 mut/Mb, the median TMB was low for both tumor types with no (0%) of cases showing≥20 mut/Mb. No (0%) of the CDC or RMC cases featured MSI-high status. Conclusions: In addition to their histologic differences, the frequencies and types of GA seen in CDC differ significantly from that seen in RMC. The opportunities for biomarker driven targeted therapies for bothCDCand RMC appear limited with rare opportunities to target GA in TKGFR and MTOR pathways for CDC. Similarly, the relatively low TMB and absence of MSI-High status in CDC and RMCalso predicts that these tumors may be resistant to immunotherapies.[Table: see text]
SEX DIFFERENCES IN THE NATURAL HISTORY AND OUTCOME OF DILATED CARDIOMYOPATHY
Authors: Brian Halliday, Ankur Gulati, Aamir Ali, Simon Newsome, Amrit Lota, Upasana Tayal, Vass Vassiliou, Monika Arzanauskaite, Cemil Izgi, Stuart Cook, Dudley Pennell, Peter Collins, John Cleland, Sanjay Prasad
Journal: Journal of the American College of Cardiology (2018)
AGE-RELATED LONG-TERM OUTCOMES FOR ALCOHOL SEPTAL ABLATION IN PATIENTS WITH HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY: EXPERIENCE FROM A LARGE INTEGRATED HEALTHCARE SYSTEM
Authors: John Kim, Somjot Brar, Ngoc Ho, Jennifer Nguyen, Kyle Greene, Prakash Mansukhani, Vicken Aharonian
Journal: Journal of the American College of Cardiology (2018)
For bleep’s sake . . .
Authors: Yasmin Akram
Journal: BMJ (2011)

I have never slept on a night shift. Maybe it’s my paranoia about missing an important call or the fact that my modest material needs don’t permit it. Whatever the reason, it has rather sensitised me to the noisy little numbered black boxes we carry around with us on duty, through which we are beckoned for all manner of undertakings. On unfortunate occasions they are also joined by their extended family, which not only make even more noise than they do but also make you feel like a badly decorated Christmas tree. And if you haven’t guessed already, the thing I am talking about is the noble bleep.

A quick Google search for effects of sound directed me to methods of torture. “Sound” comes under physical methods of torture, described as “extremely high volumes, dynamic range, low frequency, high pitched noise, intended to interfere …
IMPACT OF LEFT VENTRICULAR DIASTOLIC FUNCTION AND SURVIVAL IN PATIENTS WITH SEVERE AORTIC STENOSIS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Kimi Sato, Serge Harb, Arnav Kumar, Samir Kapadia, Stephanie Mick, Amar Krishnaswamy, Milind Desai, Brian Griffin, L. Leonardo Rodriguez, E. Murat Tuzcu, Lars Svensson, Zoran Popovic
Journal: Journal of the American College of Cardiology (2018)
Five and 10 minute Apgar scores and risks of cerebral palsy and epilepsy: population based cohort study in Sweden
Authors: Martina Persson, Neda Razaz, Kristina Tedroff, K S Joseph, Sven Cnattingius
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To investigate associations between Apgar score at five and 10 minutes across the entire range of score values (from 0 to 10) and risks of childhood cerebral palsy or epilepsy, and to analyse the effect of changes in Apgar scores from five to 10 minutes after birth in infants born ≥37 completed weeks. <h3>Design, setting, and participants</h3> Population based cohort study in Sweden, including 1 213 470 non-malformed live singleton infants, born at term between 1999 and 2012. Data on maternal and pregnancy characteristics and diagnoses of cerebral palsy and epilepsy were obtained by individual record linkages of nationwide Swedish registries. <h3>Exposures</h3> Apgar scores at five and 10 minutes. <h3>Main outcome measure</h3> Cerebral palsy and epilepsy diagnosed up to 16 years of age. Adjusted hazard ratios were calculated, along with 95% confidence intervals. <h3>Results</h3> 1221 (0.1%) children were diagnosed as having cerebral palsy and 3975 (0.3%) as having epilepsy. Compared with children with an Apgar score of 10 at five minutes, the adjusted hazard ratio for cerebral palsy increased steadily with decreasing Apgar score: from 1.9 (95% confidence interval 1.6 to 2.2) for an Apgar score of 9 to 277.7 (154.4 to 499.5) for an Apgar score of 0. Similar and even stronger associations were obtained between Apgar scores at 10 minutes and cerebral palsy. Associations between Apgar scores and epilepsy were less pronounced, but increased hazard ratios were noted in infants with a five minute Apgar score of 7 or less and a 10 minute Apgar score of 8 or less. Compared with infants with an Apgar of 9-10 at both five and 10 minutes, hazard ratios of cerebral palsy and epilepsy were higher among infants with a five minute Apgar score of 7-8 and a 10 minute Apgar score of 9-10. <h3>Conclusion</h3> Risks of cerebral palsy and epilepsy are inversely associated with five minute and 10 minute Apgar scores across the entire range of Apgar scores.
Fluid therapy in neurointensive care patients: ESICM consensus and clinical practice recommendations
Authors: Mauro Oddo, Daniele Poole, Raimund Helbok, Geert Meyfroidt, Nino Stocchetti, Pierre Bouzat, Maurizio Cecconi, Thomas Geeraerts, Ignacio Martin-Loeches, Hervé Quintard, Fabio Silvio Taccone, Romergryko G. Geocadin, Claude Hemphill, Carole Ichai, David Menon, Jean-François Payen, Anders Perner, Martin Smith, José Suarez, Walter Videtta, Elisa R. Zanier, Giuseppe Citerio
Journal: Intensive Care Medicine (2018)
Novel transgenic knockout model of basal-squamous bladder cancer.
Authors: Vasty Osei Amponsa, Zongyu Zheng, Vonn Walter, Joshua Warrick, Cathy Mendelsohn, Klaus Kaestner, Xue-Ru Wu, Jay Raman, David DeGraff
Journal: Journal of Clinical Oncology (2018)

459 Background: The recent description of the highly aggressive Basal-Squamous molecular subtype of bladder cancer (BLCa) requires the development of new in vivo models for the study of this clinical entity. Although loss of the transcription factor Forkhead box A1 ( FOXA1) is significantly associated with the Basal-Squamous subtype, cooperating genetic alterations are unknown. Herein, we identify genetic alterations that potentially cooperate with FOXA1 loss to drive tumorigenesis and/or the Basal-Squamous phenotype and develop a novel transgenic model for the study of Basal-Squamous BLCa. Methods: We interrogated The Cancer Genome Atlas (TCGA) BLCa study to identify common genetic alterations associated with FOXA1 copy number (CN) loss. Based on our results, we utilized a bladder-specific Cre-LoxP ( Uroplakin II-Cre) to constitutively knock-out (KO) Foxa1 and/or Pten in mouse urothelium. Two cohorts of mice were aged for 6 and 12 months, and a third cohort was exposed to the bladder-specific carcinogen N-butyl-(4-hydroxybutyl)-nitrosamine (BBN; 0.05%) for 12 weeks. Following all experiments, the bladder tissue was isolated and characterized. Results: The TCGA data revealed that combined CN loss of both FOXA1 and PTEN occurs in 17% of MI BLCa patients. At 6 months of age, our mice developed urothelial hyperplasia, whereas at 12 months of age, double KO ( Foxa1 -/- /Pten -/- ) mice developed carcinoma in situ (CIS) with SqD, enriched for basal (Krt5/6 and 14) and reduced in luminal (Gata3 and Pparγ) markers. Increased tumor stage was significantly associated with combined KO of at least one allele of Foxa1 and Pten following BBN exposure. Moreover, upregulation of apoptosis related genes was observed by RNA-sequencing data. Conclusions: In advanced BLCa, CN loss of FOXA1 and PTEN is common. Genetic ablation of Foxa1 and Pten results in CIS with SqD and a pathologic profile consistent with the Basal-Squamous subtype and accelerated tumor onset following carcinogen exposure. Therefore, we describe the development of a novel model for the study of Basal-Squamous BLCa potentially useful for preclinical studies.
Epigenome analysis links gene regulatory elements in group 2 innate lymphocytes to asthma susceptibility
Authors: Ralph Stadhouders, Bobby W.S. Li, Marjolein J.W. de Bruijn, Antonio Gomez, Tata Nageswara Rao, Hans Jörg Fehling, Wilfred F.J. van IJcken, Ai Ing Lim, James P. Di Santo, Thomas Graf, Rudi W. Hendriks
Journal: Journal of Allergy and Clinical Immunology (2018)
18F-FDG PET/CT Findings in a Patient With IgG4-Related Sclerosing Mesenteritis
Authors: Zhanli Fu, Guoqian Chen, Meng Liu, Ziao Li, Qian Li
Journal: Clinical Nuclear Medicine (2018)

Abstract A large mass in the abdomen was revealed by ultrasonography on a 68-year-old woman presenting with abdominal pain and weight loss. To exclude the malignancy, an 18 F-FDG PET/CT was performed, which showed a solitary soft tissue mass with heterogeneous 18 F-FDG avidity at the root of small bowel mesentery. Because of the elevation of inflammatory markers and serum IgG4 level, IgG4-related sclerosing mesenteritis was suspected, which was proved by the subsequent biopsy. The mass gradually shrunk and ultimately disappeared in 6 months after a low-dose steroid therapy.
COMPARATIVE EFFECTIVENESS AND SAFETY OF CONTEMPORARY DRUG-ELUTING STENTS FOR LEFT MAIN CORONARY ARTERY DISEASE: A POOLED ANALYSIS OF 3 PROSPECTIVE, MULTI-CENTER, CLINICAL-PRACTICE REGISTRIES
Authors: Duk-Woo Park, Pil Hyung Lee, Osung Kwon, Jung-Min Ahn, Cheol Hyun Lee, Do-Yoon Kang, Jung-Bok Lee, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2018)
Basic surgical anatomy of the head and neck
Authors: E Broughton
Journal: BMJ (2009)

The Royal College of Surgeons basic surgical anatomy course is a comprehensive journey through the head and neck. It provides gems of knowledge about key landmarks and danger areas, and the impeccable standard of teaching and flow of anatomy are both enjoyable and educational.

Anyone with an interest in surgery (particularly ear, nose, and throat; maxillofacial; plastic; and neurosurgery) will benefit enormously from this course, whether preparing for exams or anatomy demonstrating jobs or just assisting in their next operation. However, I think the scope is much greater and any professional who needs to understand head and neck structures—such as anaesthetists, dentists, ophthalmologists, and radiologists—will also be able to develop his or her knowledge and thus skill base.

The course is held at the Royal College of Surgeons in London …