tbuckley/cabot-search huggingface dataset:
Canada's global health role: supporting equity and global citizenship as a middle power
Authors: Stephanie A Nixon, Kelley Lee, Zulfiqar A Bhutta, James Blanchard, Slim Haddad, Steven J Hoffman, Peter Tugwell
Journal: The Lancet (2018)

Canada's history of nation building, combined with its status as a so-called middle power in international affairs, has been translated into an approach to global health that is focused on equity and global citizenship. Canada has often aspired to be a socially progressive force abroad, using alliance building and collective action to exert influence beyond that expected from a country with moderate financial and military resources. Conversely, when Canada has primarily used economic self-interest to define its global role, the country's perceived leadership in global health has diminished. Current Prime Minister Justin Trudeau's Liberal federal government has signalled a return to progressive values, driven by appreciation for diversity, equality, and Canada's responsibility to be a good global citizen. However, poor coordination of efforts, limited funding, and the unaddressed legacy of Canada's colonisation of Indigenous peoples weaken the potential for Canadians to make meaningful contributions to improvement of global health equity. Amid increased nationalism and uncertainty towards multilateral commitments by some major powers in the world, the Canadian federal government has a clear opportunity to convert its commitments to equity and global citizenship into stronger leadership on the global stage. Such leadership will require the translation of aspirational messages about health equity and inclusion into concrete action at home and internationally.
Résultats de la dissection sous muqueuse rectale en France: étude retrospective multicentrique en centres experts
Authors: J Albouys, MA Guillaumot, V Lepilliez, S Chaussade, M Pioche, S Leblanc, M Barret, R Legros, F Prat, J Rivory, D Sautereau, T Ponchon, J Jacques
Journal: Endoscopy (2018)

La dissection sous-muqueuse endoscopique est devenue le traitement préférentiel des lésions pré-cancéreuses ou cancéreuses rectales superficielles étendues. Malgré une pratique croissante dans le monde occidental, peu d'études européennes ont été rapportées. Les premiers résultats français étaient loin de ceux rapportés par les équipes japonaises: résection en bloc: 64%; R0: 53%. Depuis ces premiers résultats, des centres experts se sont perfectionnés au japon et sur modèles animaux et des progrès stratégiques ont été publiés. Nous rapportons ici les résultats d'une étude multicentrique française de quatre équipes réalisant plus de 50 dissections sous-muqueuses annuelles.
Burden of Metastatic Castrate Naive Prostate Cancer Patients, to Identify Men More Likely to Benefit from Early Docetaxel: Further Analyses of CHAARTED and GETUG-AFU15 Studies
Authors: Gwenaelle Gravis, Jean-Marie Boher, Yu-Hui Chen, Glenn Liu, Karim Fizazi, Michael A. Carducci, Stephane Oudard, Florence Joly, David M. Jarrard, Michel Soulie, Mario J. Eisenberger, Muriel Habibian, Robert Dreicer, Jorge A. Garcia, Maha H.M. Hussain, Manish Kohli, Nicholas J. Vogelzang, Joel Picus, Robert DiPaola, Christopher Sweeney
Journal: European Urology (2018)
“High holidays” are linked to increased risk of fatal traffic crashes
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

The popular American annual counterculture holiday “4/20,” which is celebrated by mass consumption of cannabis at 4 20 pm on 20 April, is associated with an increased risk of fatal traffic crashes, a study has found.1

To examine the link between cannabis use and fatal vehicle crashes, Canadian researchers looked at data from the United States National Highway Traffic Safety Administration’s fatality analysis reporting system, …
Anastomose gastro-jéjunale par prothèse d'apposition luminale (Hot-Axios) sous écho-endoscopie pour obstruction d'anastomose hépatico-jéjunale: expérience préliminaire sur 4 cas
Authors: B Bordacahar, M Barret, S Leblanc, B Brieau, S Chaussade, F Prat
Journal: Endoscopy (2018)

Récemment, de nouvelles prothèses métalliques dites d'apposition luminale ont été développées permettant de réaliser une anastomose entre 2 organes adjacents.(1 – 2) La faisabilité d'une anastomose gastro-jéjunale (AGJ) endoscopique grâce à ces prothèses Hot-Axios (Boston Scientific, Marlborough, USA) a récemment été étudiée dans le cadre d'obstruction digestive. Nous rapportons notre expérience initiale de cette technique dans le cas d'obstruction d'anse biliaire après chirurgie hépato-bilio-pancréatique.
The role of the patient-generated subjective global assessment (PG-SGA) in nutritional evaluation for advanced colorectal cancer
Authors: Digant Gupta, Christopher G. Lis, Carolyn A. Lammersfeld, Jessica L. Burrows, Sharon M. Walker, James F. Grutsch
Journal: Cancer Research (2004)

1404  Malnutrition is a strong predictor of morbidity and mortality in cancer. Serum albumin is the most commonly used single measure to assess nutritional status in clinical oncology. At our center, we use serum albumin in conjunction with the Patient-Generated Subjective Global Assessment (PG-SGA) to assess nutritional status in cancer patients. The PG-SGA calculates a composite nutritional score after combining information from food intake, weight change, nutrition-related symptoms, and performance status. The PG-SGA categorizes patients into three distinct classes of nutritional status; well nourished (PG-SGA-A), moderately malnourished (PG-SGA-B) and severely malnourished (PG-SGA-C). The PG-SGA, however, has not been extensively validated in clinical cancer settings and little is known about the relationship between the PG-SGA and serum albumin. We hypothesized that the PG-SGA provides additional information about nutritional status, as it captures patient-derived behavioral and outcome data. We explored this issue by evaluating the nutrition outcomes in a consecutive case series of 234 colorectal cancer patients treated at Cancer Treatment Centers of America at Midwestern Regional Medical Center between January 1995 and March 2001. All patients had a histologically confirmed diagnosis of stage III or IV colorectal cancer. The mean scores of serum albumin were compared across the three classes of baseline PG-SGA using analysis of variance (ANOVA). The correlation between the PG-SGA and serum albumin was studied using Pearson’s correlation coefficient. We found a modest statistically significant correlation between the baseline PG-SGA and serum albumin (table 1). ANOVA revealed statistically significant differences in the mean values of serum albumin across the 3 baseline PG-SGA categories (table 1). Multiple pair-wise comparisons using Scheffe’s method showed that the mean scores of serum albumin across all 3 categories of the PG-SGA were statistically significantly different from each other (table 1). While the normal serum albumin levels range from 4-6 g/dl, in our analysis, we report that levels as high as 4.9 g/dl may actually indicate a degree of nutritional risk, and therefore, require a more detailed nutritional assessment. Collectively, these results suggest that addition of the PG-SGA to the nutritional assessment tool kit provides a more comprehensive assessment of nutritional status in advanced colorectal cancer. Further studies need to focus on more extensive validation of the PG-SGA in clinical cancer settings.
First-line avelumab + axitinib therapy in patients (pts) with advanced renal cell carcinoma (aRCC): Results from a phase Ib trial.
Authors: Toni K. Choueiri, James M. G. Larkin, Mototsugu Oya, Fiona C. Thistlethwaite, Marcella Martignoni, Paul D. Nathan, Thomas Powles, David F. McDermott, Paul B. Robbins, David D. Chism, Daniel C. Cho, Michael B. Atkins, Michael S. Gordon, Sumati Gupta, Hirotsugu Uemura, Yoshihiko Tomita, Anna Compagnoni, Alessandra di Pietro, Brian I. Rini
Journal: Journal of Clinical Oncology (2017)

4504 Background: Combining an immune checkpoint inhibitor with a targeted antiangiogenic agent may leverage complementary mechanisms of action for treatment of aRCC. Avelumab is a fully human anti–PD-L1 IgG1 antibody with clinical activity in various tumor types; axitinib, a VEGF receptor inhibitor, is approved for second-line treatment of aRCC. JAVELIN Renal 100 (NCT02493751) is a phase Ib study evaluating safety and clinical activity of avelumab + axitinib in treatment-naïve pts with aRCC; updated results are reported here. Methods: Eligible pts had confirmed clear-cell aRCC, ≥1 measurable lesion, fresh or archival tumor specimen, ECOG PS ≤1, and no prior systemic therapy. Pts received avelumab 10 mg/kg IV Q2W + axitinib 5 mg orally BID until progression, unacceptable toxicity, or withdrawal. Endpoints included safety (NCI CTCAE v4.03) and objective response (RECIST v1.1). Results: As of Dec 30, 2016, 55 pts (median age 60.0 yrs [range 42.0–76.0]; 76.4% male; 34.5% ECOG PS = 1) were enrolled. 54 pts were treated with avelumab for a median of 24.1 wks (range 2.0–62.0); 55 pts were treated with axitinib for a median of 25.3 wks (range 3.0-61.0). 51 pts (92.7%) had an avelumab-related adverse event (AE) with the therapy combination, the most common (≥30% any grade) were fatigue and diarrhea (30.9% each). 10 pts (18.2%) had a max grade 3 and 1 pt (1.8%) had a max grade 4 avelumab-related AE. 52 pts (94.5%) had an axitinib-related AE with the therapy combination; the most common (≥30% any grade) were diarrhea (52.7%), hypertension (45.5%), dysphonia (43.6%), and fatigue (43.6%). 24 pts (43.6%) had a max grade 3 and 5 pts (9.1%) had a max grade 4 axitinib-related AE. 2 deaths occurred in the study during the reporting period: 1 due to progression and 1 related to both treatments (myocarditis). An AE led to discontinuation of avelumab in 5 pts (9.1%) and axitinib in 4 pts (7.3%). Confirmed ORR was 54.5% (95% CI 40.6–68.0) based on 2 CR and 28 PR. Unconfirmed ORR was 60.0% (95% CI 45.9–73.0). Conclusions: The safety profile of the combination of avelumab + axitinib appears manageable and consistent with those agents administered as monotherapy, and early encouraging antitumor activity was observed. Follow-up is ongoing. Clinical trial information: NCT02493751.
Nasal Biomarkers Characterization In Lebrikizumab Bronchoscopy Study (CLAVIER)
Authors: Fang Cai, Francis Abreu, Han Ting Ding, David Choy, Meire Bremer, Tracy Staton, Rich Erickson, Kun Peng, Jian Shuang Wang, Amelia Au-Yeung, Trevor T. Hansel, Leif Bjermer, Cecile Holweg, Karl Yen, John G. Matthews, Heleen Scheerens
Journal: Journal of Allergy and Clinical Immunology (2018)
Former USA Gymnastics team doctor sentenced for abusing hundreds of girl athletes
Authors: Owen Dyer
Journal: BMJ (2018)

Larry Nassar, a former doctor with USA Gymnastics and Michigan State University (MSU) who sexually abused hundreds of young athletes under his care, has received a sentence of 40 to 175 years in prison after a trial that ended with a week of harrowing victim impact statements from 156 young women. Nassar pleaded guilty to nine counts of first degree sexual assault.1

Should Nassar, 54, complete the sentence of at least 40 years, he would then begin serving a 60 year federal sentence that he received in December for keeping images of child abuse on his computer. “I just signed your death warrant,” Judge Rosemarie Aquilina told him.

“It is my honour and privilege to sentence you,” she added. “Because, sir, you do not deserve to walk outside of a prison ever again.”

The hearing triggered a cascade of resignations from the board of USA Gymnastics and, following Nassar’s sentencing, the long serving president of MSU, Lou Anna Simon, announced that she was leaving the job. She had previously declared her determination to stay, but reconsidered following a scathing editorial in the student newspaper and the announcement of …
Serum Periostin in Eosinophilic Oesophagitis and Proton Pump Inhibitor-Responsive Oesophageal Eosinophilia
Authors: Daiana Guillen Vera, Natividad De Las Cuevas, Ruth Barranco, Jesús Fernández-Crespo, Maria Del Carmen Dieguez
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 17320: Inhibition of Ceramide Synthesis Preserves Cardiac Function and Increases Survival in Doxorubicin-induced Cardiomyopathy
Authors: Ruiping Ji, Jennifer Y Chang, Xianghai Liao, Xiaokan Zhang, Peter Kennel, Estibaliz Castillero, Danielle Brunjes, Hirokazu Akashi, Shunichi Homma, Ira Goldberg, Paul Christian Schulze
Journal: Circulation (2015)

Background: Previous studies have linked increased ceramide and dihydroceramide (DHC) synthesis to cardiotoxicity. However, the effects of ceramide synthesis inhibition on doxorubicin (DOX)-induced cardiomyopathy are unclear. Hypothesis: Inhibition of de novo ceramide synthesis by myriocin maintains heart function and survival rate. Methods: C57BL/6J mice (8 wks, n=52) were treated with DOX (3 mg/kg every other day for 2 wks) with or without myriocin (0.3 mg/kg). Cardiac function was assessed by echocardiography. AC16 cardiomyocyte-like cells were incubated with DOX in the presence or absence of myriocin (10 uM). Ceramides were analyzed by LC/MS lipidomics. Reactive oxygen species (ROS) were measured by FACS (CellROX) and mitochondrial function determined by Seahorse analyzer. Results: In DOX-treated mice, inhibition of ceramide synthesis by myriocin preserved cardiac fractional shortening (29.2±2.7 vs 36.9±1.4% in myriocin; p&lt;0.05), left ventricular systolic diameter dilation (3.2±0.1 vs 2.97±0.8 mm, p&lt;0.05), running endurance (8.5 vs 17.5 min; p&lt;0.05) and survival rates (35 vs 90% in myriocin, p&lt;0.001). DOX increased cardiac total ceramides (+70%; p&lt;0.001) and DHC (+73%; p&lt;0.05); these increases were prevented by myriocin. Cardiac apoptosis in these cells was increased 4.1 fold by DOX and reduced by 50% with myriocin (p&lt;0.05). In cells, DOX increased cellular ceramide content (+112.4%, p&lt;0.01), especially C14 (+69%; p&lt;0.05), C16 (+144%; p&lt;0.01), C18 (+53%; p&lt;0.05), C22 (+98%; p&lt;0.05), C24 (+83.5%; p&lt;0.01) and C24:1(+86%; p&lt;0.05). Interestingly, ceramide accumulation in mitochondria of DOX-treated cells (+125%; p&lt;0.05) was associated with decreased mitochondrial respiration (-76%; p&lt;0.05) and respiratory capacity (-88%; p&lt;0.05). Myriocin treatment decreased very long-chain ceramides (-52%; p&lt;0.05), reduced apoptosis (-23%; p&lt;0.01), and prevented proteolysis of actin protein ubiquitination (-31%; p&lt;0.05). Also, myriocin inhibited DOX-induced increase of ROS (+32%; p&lt;0.05). Conclusion: Cardiomyocyte ceramide accumulation, especially in mitochondria, is associated with mitochondrial dysfunction, cardiotoxicity and reduced survival. Pharmacological inhibition of ceramide synthesis may prevent lipotoxicity.
Abstract 12056: Factors Affecting the Decision to Undergo Genetic Testing in Patients with Hypertrophic Cardiomyopathy
Authors: Patricia L Arscott, Christina M Rigelsky, Rocio T Moran, Maran Thamilarasan, Nicholas G Smedira, Bruce W Lytle, Harry M Lever, Milind Y Desai
Journal: Circulation (2011)

Introduction:  Genetic testing for hypertrophic cardiomyopathy (HCM) has emerged as an important tool to identify at-risk family members who would potentially benefit from periodic cardiac screening for development of overt HCM phenotype. We sought to identify potential factors that play a role in the decision-making to pursue genetic testing in a HCM proband.   Methods:  This study included 108 consecutive adults with HCM seen for genetic counseling between 12/2009 and 4/2011. We collected data on demographics, children, siblings, type of health insurance, family history of sudden cardiac death (SCD) and HCM, presence of internal defibrillator (ICD), need for surgical myectomy and whether they had commercially available genetic testing for at least 11 genes most commonly associated with HCM.   Results:  The mean age of the study population at presentation was 52 ± 14 years with 75 (69 %) males. Overall, 20 (18 %) and 52 (48 %) patients had family history of HCM and SCD, respectively. The mean number of children and siblings were 2 ± 1 and 3 ± 2, respectively. Thus far, 62 (58 %) patients have undergone surgical myectomy and 23 (21 %) patients have had an ICD placed. Two (2 %) patients had no insurance, 21 (19 %) had medicare/medicaid and 85 (79 %) had private insurance. Of the 55 (51 %) probands that underwent genetic testing, 16 (31 %) were gene positive, while 5 (9 %) had a variant of unknown significance and 33 (60 %) were negative. Of the 16 gene-positive individuals, family history of HCM and SCD were absent in 8 (50 %) and 7 (44 %), respectively. Logistic regression analyses of potential factors associated with the decision to undergo genetic testing are shown in the Figure.   Conclusion:  The decision to undergo genetic testing was independently associated with a younger age at presentation, number of children, presence of ICD and a family history of SCD. The type of health insurance did not play a significant role in the decision-making to undergo genetic testing.
Reply to the Letter to the Editor on ‘Cost–opportunity analysis in clinical oncology: from the “wild far-west” to a correct integration of the disciplines, avoiding the “war of the worlds”’, by D. Tassinari et al. (Ann Oncol 2006; 17: 877)
Authors: M. Colleoni, S. Gelber, A. Goldhirsch
Journal: Annals of Oncology (2005)
Abstract 15062: Incremental Prognostic Utility of LV Global Longitudinal Strain and Functional Capacity in Asymptomatic Patients With Significant Primary Mitral Regurgitation and Preserved Left Ventricular Ejection Fraction Undergoing Rest-Stress Echocardiography
Authors: Amgad Mentias, Peyman Naji, Tyler Barr, A. Marc Gillinov, L. Leonardo Rodriguez, Tomislav Mihaljevic, Joseph F Sabik, Brian P Griffin, Milind Y Desai
Journal: Circulation (2015)

Background: Outcomes after mitral valve (MV) surgery for primary mitral regurgitation (PMR) are excellent; however surgical timing in asymptomatic PMR &amp; preserved left ventricular ejection fraction (LVEF) remains challenging. We assessed the incremental utility of resting LV-global longitudinal strain (LV-GLS) &amp; exercise variables in asymptomatic patients with ≥3+ PMR &amp; preserved LVEF (≥60%) who underwent rest-stress echocardiography. Methods: We included 737 such patients (58±13 years, 68% men) between 2000-11. Clinical, resting (including LV-GLS using Velocity Vector Imaging &amp; right ventricular systolic pressure or RVSP) &amp; exercise stress echo (metabolic equivalents or METs) data were recorded. Society of Thoracic Surgeons (STS) score was calculated. Primary events were death &amp; heart failure admission. Results: Hypertension, atrial fibrillation (AF) and coronary artery disease were seen in 48%, 13% &amp; 10% patients. Posterior, anterior &amp; bileaflet prolapse were noted in 46%, 9% &amp; 45% (20% had flail). Mean STS score, resting LVEF, resting RVSP, exercise MET’s &amp; % age-gender predicted MET’s were 1.5±1, 62±2%, 31±12 mmHg, 9.8±3 &amp; 115±27 respectively. 65% underwent MV surgery with mean time to surgery 13±22 months. At 6.2±3 years, events occurred in 61 (8%) patients (death in 33 patients). On multivariable Cox survival analysis, higher rest RVSP (Hazard ratio or HR 1.04), lower % age-gender predicted METS (HR 1.11), lower LV-GLS (HR 1.42), higher STS score (HR 1.12) &amp; AF (HR 2.23) were significantly associated with events (all p&lt;0.05). Association of MV surgery (time-dependent covariate) with outcomes was not significant (HR 0.63 [0.38-1.07, p=0.1). Figure 1a shows an incremental model with association to outcomes &amp; 1b shows survival curves, based on LV-GLS better/worse than median (-21.7%). Conclusions: In asymptomatic patients with ≥3+ PMR &amp; preserved LVEF, lower baseline LV-GLS &amp; %age-gender predicted METs are associated with long-term adverse events.
NBCe1-A Regulates Proximal Tubule Ammonia Metabolism under Basal Conditions and in Response to Metabolic Acidosis
Authors: Hyun-Wook Lee, Gunars Osis, Autumn N. Harris, Lijuan Fang, Michael F. Romero, Mary E. Handlogten, Jill W. Verlander, I. David Weiner
Journal: Journal of the American Society of Nephrology (2018)

Renal ammonia metabolism is the primary mechanism through which the kidneys maintain acid-base homeostasis, but the molecular mechanisms regulating renal ammonia generation are unclear. In these studies, we evaluated the role of the proximal tubule basolateral plasma membrane electrogenic sodium bicarbonate cotransporter 1 variant A (NBCe1-A) in this process. Deletion of the NBCe1-A gene caused severe spontaneous metabolic acidosis in mice. Despite this metabolic acidosis, which normally causes a dramatic increase in ammonia excretion, absolute urinary ammonia concentration was unaltered. Additionally, NBCe1-A deletion almost completely blocked the ability to increase ammonia excretion after exogenous acid loading. Under basal conditions and during acid loading, urine pH was more acidic in mice with NBCe1-A deletion than in wild-type controls, indicating that the abnormal ammonia excretion was not caused by a primary failure of urine acidification. Instead, NBCe1-A deletion altered the expression levels of multiple enzymes involved in proximal tubule ammonia generation, including phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and glutamine synthetase, under basal conditions and after exogenous acid loading. Deletion of NBCe1-A did not impair expression of key proteins involved in collecting duct ammonia secretion. These studies demonstrate that the integral membrane protein NBCe1-A has a critical role in basal and acidosis-stimulated ammonia metabolism through the regulation of proximal tubule ammonia-metabolizing enzymes.
Margaret McCartney: Doctors and families must be able to work together for safer care
Authors: Margaret McCartney
Journal: BMJ (2018)

A little boy, Jack Adcock, is dead.This is horrendous, and accounts of the background to the case clearly show mistakes and shortcomings that could and should have been avoided.But how? Jack's included clinical mistakes and numerous systemic ones, particularly regarding staff absence and IT systems.This was the "Swiss cheese" model writ large and fatal: the holes in the system aligned and let tragedy happen.
Hemophilia Gene Therapies Show Promise
Authors: Jennifer Abbasi
Journal: JAMA (2018)

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