tbuckley/cabot-search huggingface dataset:
Younger, female, and BME doctors are more likely to have revalidation deferred
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Deferral of revalidation is likelier among younger doctors, women, and doctors from black and minority ethnic backgrounds, a major impact study has found.1

The three year review by the UK Medical Revalidation Evaluation Collaboration (UMbRELLA) found that the General Medical Council’s objective to bring most doctors into a governed system of medical revalidation had largely been achieved since it was introduced in 2012. But it noted that engagement had generally been less straightforward for doctors working for more than one organisation.

Responsible officers (the individuals within designated bodies, such as NHS employers, who have overall responsibility for revalidation) can make one of three recommendations to the GMC after a five year revalidation period: approval, deferral, or non-engagement with the revalidation process. Deferral can be recommended if there is not enough evidence to recommend a doctor’s revalidation, if a doctor is under …
Neonates colonized with pathogenic bacteria in the airways have a low‐grade systemic inflammation
Authors: N. Rahman Fink, B. L. Chawes, J. Thorsen, J. Stokholm, K. A. Krogfelt, S. Schjørring, M. Kragh, K. Bønnelykke, S. Brix, H. Bisgaard
Journal: Allergy (2018)

Abstract Background and objectives The development of childhood asthma is associated with neonatal colonization with pathogenic bacteria in hypopharynx. Furthermore, established asthma is associated with systemic low‐grade inflammation. We here report on the association between neonatal colonization with pathogenic bacteria in hypopharynx and the development of systemic low‐grade inflammation. Methods Bacterial colonization of the hypopharynx with Moraxella catharralis, Haemophilus influenzae, and/or Streptococcus pneumoniae was assessed in asymptomatic children from the Copenhagen Prospective Studies on Asthma in Childhood 2000 ( COPSAC 2000 ) cohort at age 1 month by culturing technique (N = 238) and by quantitative polymerase chain reaction ( qPCR ) technique (N = 249) and in the COPSAC 2010 cohort by culturing at age 1 month (N = 622) and again at age 3 months (N = 613). Systemic low‐grade inflammation was determined in both cohorts at age 6 months by measuring plasma levels of high‐sensitivity C‐reactive protein (hs‐ CRP ), tumor necrosis factor‐α ( TNF ‐α), and interleukin‐6 ( lL ‐6). Results In both cohorts, bacterial colonization was associated with increased levels of hs‐ CRP : COPSAC 2000 , 1 month culturing (geometric mean ratio of colonized/noncolonized [95% CI ]), 1.39 [0.97‐2.01], P = .08; 1 month qPCR , 1.55 [1.14‐2.10], P &lt; .01; COPSAC 2010 , 1 month, 1.52 [1.23‐1.87], P &lt; .01; and 3 month, 1.57 [1.30‐1.90], P &lt; .01. A multiparametric principal component analysis incorporating hs‐ CRP , TNF ‐α, and IL ‐6 confirmed a systemic inflammatory profile in children colonized with M. catharralis, H. influenzae . and/or S. pneumoniae in the hypopharynx compared to noncolonized children ( P ‐values &lt; .05). Conclusion The composition of the upper airway microbiome in early life may cause systemic low‐grade inflammation.
P116The creatinine to uromodulin ratio in serum predicts major cardiovascular events independently from the presence of type 2 diabetes
Authors: A Leiherer, A Muendlein, C H Saely, E M Brandtner, A Mader, K M Ebner, B Larcher, C Heinzle, P Fraunberger, H Drexel
Journal: Cardiovascular Research (2018)

Objective: To study structural parameters of vessel wall, lipid and inflammatory biochemical parameters in patients with arterial hypertensios (AH) and abdominal obesity (AO).Design and methods: 108 patients (mean age 44,8160,95) were randomized into 2 groups.The Gr.1 included 70 subjects with AH and AO.The Gr.2 included 38 subjects without AO.The parameters of sphygmography, blood pressure monitoring; biochemical parameters (total cholesterol, LDL-chol, HDL-chol, triglycerides, malonic dialdehyde and inflammatory markers -homocysteine and hs-CRP were estimated.Results: In Gr.1 there were registered: significant increase in sphygmography indexis (pulse wave velocity PWV, cardio-ankle vascular index ), in mean 24-hour and mean daytime systolic BP and variability, in total cholesterol, LDL-chol, triglyceride and MD levels, homocysteine and hs-CRP level, compared to the patients in group 2.In Gr.1 there were registered positive correlation between inflammatory and lipid markers with parameters of sphygmography and blood pressure monitoring.It was shown that with an increase in total cholesterol level >5.0 mmol/l, the risk of high rate PWV in patients with AH and AO increased by 15 times. Conclusion:The revealed correlations of inflammatory and lipid markers with indices of vascular wall rigidity once again exhibit a high risk of cerebrovascular complications in patients with AH and metabolic disorders
Hepatitis C care cascade in the country of Georgia after 2 years of starting national hepatitis C elimination program
Authors: T. Tsertsvadze, A. Gamkrelidze, N. Chkhartishvili, L. Gvinjilia, A. Abutidze, L. Sharvadze, M. Butsashvili, D. Metreveli, M. Ezugbaia, T. Kuchuloria, S. Shadaker, M. Nasrullah, B. Skaggs, V. Kvaratskhelia, S. Zeuzem, N. Afdhal, S. Arora, K. Thornton, F. Averhoff
Journal: Journal of Hepatology (2018)
Abstract 17778: Cellular and Functional Defects Contributing to Dilated Cardiomyopathy in SCN5A D1275N Mice
Authors: Dina M Stroud, Lynn Hall, Hyun S Hwang, Franz Baudenbacher, Bjorn Knollmann, Dan M Roden
Journal: Circulation (2014)

Background:  The D1275N  SCN5A  mutation is associated with dilated cardiomyopathy (DCM) in humans. We have previously reported that in 12 week old mice carrying humanized  SCN5A  alleles, DCM is evident by echo in those homozygous for D1275N (DN/DN) compared to those homozygous for the wild-type allele (H/H), with striking conduction slowing and disorganization by ECG and mapping. Here we compared cellular structure, expression of sodium channel partners, and calcium handling in young (3-week) DN/DN versus H/H mice to identify early changes and thereby illuminate mechanisms for DCM in this model.   Methods and Results:  By 3 weeks, QRS duration was markedly prolonged and disorganized in DN/DN mice (HH, n=11, 9.8 ± 0.2; DN/DN, n=9, 22.3 ± 2.2 P ratio ) and SR calcium stores (H/H, 0.85±0.08; DN/DN, 0.92±0.07, F ratio ) were not statistically significantly different in DN/DN compared to H/H, arguing against aberrant calcium handling as a primary driver of DCM in these mice. Similarly, there were no differences in alpha-actinin or ryanodine receptor expression patterns by immunofluorescence. Expression of the sodium channel partners (and DCM associated genes) dystrophin and syntrophin were identical between H/H and DN/DN by immunostaining and Western blotting.   Conclusions:  Our present results support the hypothesis that slow, abnormal conduction detected by ECG at 3 weeks of age is a primary factor underlying DCM development.
Efficacy and Safety of Glecaprevir/Pibrentasvir in Patients with HCV Genotype 5 or 6 Infection: The ENDURANCE-5,6 Study
Authors: T. Asselah, T. Tran, K. Alves, T. Nguyen, F. Wong, A. Mahomed, S.G. Lim, S. Lee, A. Abergel, J. Sasadeusz, P. Krishnan, Z. Zhang, A. Pocalla, R. Trinh, E. Gane
Journal: Journal of Hepatology (2018)
Quality and Safety in Health Care, Part XXXVIII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2018)

The CathPCI Registry was started in 1998 to improve health quality for those patients having a percutaneous coronary intervention or diagnostic cardiac catheterization. This registry studies complications, outcomes from placing coronary artery stents of different types, appropriateness of performing the procedures, special indications for performing the procedures, safety of devices, patient characteristics, possible relationships between volume of procedures and quality, models to adjust for patient risk, and so on. The registry encourages using the information to promote research and quality improvement and public reporting of the data.
Metabolic heterogeneity on baseline 18FDG-PET/CT scan is a predictor of outcome in primary mediastinal B-cell lymphoma
Authors: Luca Ceriani, Lisa Milan, Maurizio Martelli, Andrés J. M. Ferreri, Luciano Cascione, Pier Luigi Zinzani, Alice Di Rocco, Annarita Conconi, Anastasios Stathis, Franco Cavalli, Monica Bellei, Kelly Cozens, Elena Porro, Luca Giovanella, Peter W. Johnson, Emanuele Zucca
Journal: Blood (2018)
P503Inter-subject variability explains juxtaposed effects in pharmacological treatments: an in-silico approach for the personalization of atrial fibrillation drug treatments
Authors: A Liberos, I Hernandez-Romero, A S De La Nava, M Rodrigo, A Bueno-Orovio, B Rodriguez, M S Guillem, F Atienza, A M Climent, F Fernandez-Aviles
Journal: Cardiovascular Research (2018)

Fig. 1B).Measures were grouped by zones distinguish between the normal zone, the heterogeneous tissue present at the scar border zone and the conduction channels.Results: During pacing, APD presented values of 194 6 48 ms in the the normal zone, 222 6 52 ms in the heterogeneous tissue present at the scar border zone, 281 6 61 ms in the conduction channels, differences were identified between the regions under study (p<0.05).CV was 75.6 6 12.2 cm/s, 52.5 6 7.2 cm/s, 33.7 6 7.9 cm/s (p<0.05) for the same areas listed before.Finally, during ventricular tachycardia CV in the border area of infarction presented values of 17.3 6 9.2 cm/s whereas APD was 213 6 12 ms, the area farthest from the infarct presented values of 52.4 6 12.3 cm/s and 181 6 9 ms (p<0.05) (Fig. 1C).Conclusions: Initiation and maintenance or ventricular tachycardia is associated with heterogeneity on APD duration and CVs.This chronic infarction swine model is a consistent ventricular tachycardia model, which simulates realistic tachyarrhythmias.High-resolution optical mapping in this model is useful to study the mechanism of ventricular tachycardia and evaluate the effects of different therapies.
Ductular reaction cells promote angiogenesis via SLIT2/ROBO1 pathway in chronic liver disease
Authors: M. Coll, E. Garcia-Pras, B. Aguilar-Bravo, J. Gallego, D. Blaya, J. Vallverdú, L. Perea, I. Graupera, E. Pose, J. Lozano, R. Bataller, P. Ginès, J.-G. Geng, M. Fernandez, P. Sancho-Bru
Journal: Journal of Hepatology (2018)
Combination of HBV serological markers to predict the burden and productivity of intrahepatic HBV reservoir and disease progression in HBeAg negative Chronic Hepatitis B
Authors: V. Svicher, R. Salpini, L. Colagrossi, D.D. Carlo, A. Battisti, L. Piermatteo, N. Hansi, F.C. Silberstein, C.F. Perno, U.S. Gill, P. Kennedy
Journal: Journal of Hepatology (2018)
Liver biopsy derived induced pluripotent stem cells provide unlimited supply for the generation of hepatocyte-like cells
Authors: D. Calabrese, G. Roma, S. Bergling, W. Carbone, V. Mele, S. Nuciforo, I. Fofana, B. Campana, D. Szkolnicka, D. Hay, J. Tchorz, T. Bouwmeester, S. Wieland, M. Heim
Journal: Journal of Hepatology (2018)
Inhibition of the Wnt/β-Catenin Pathway Overcomes Resistance to Enzalutamide in Castration-Resistant Prostate Cancer
Authors: Zhuangzhuang Zhang, Lijun Cheng, Jie Li, Elia Farah, Nadia M. Atallah, Pete E. Pascuzzi, Sanjay Gupta, Xiaoqi Liu
Journal: Cancer Research (2018)

Enzalutamide is a second-generation nonsteroidal antiandrogen clinically approved for the treatment of castration-resistant prostate cancer (CRPC), yet resistance to endocrine therapy has limited its success in this setting. Although the androgen receptor (AR) has been associated with therapy failure, the mechanisms underlying this failure have not been elucidated. Bioinformatics analysis predicted that activation of the Wnt/β-catenin pathway and its interaction with AR play a major role in acquisition of enzalutamide resistance. To validate the finding, we show upregulation of β-catenin and AR in enzalutamide-resistant cells, partially due to reduction of β-TrCP-mediated ubiquitination. Although activation of the Wnt/β-catenin pathway in enzalutamide-sensitive cells led to drug resistance, combination of β-catenin inhibitor ICG001 with enzalutamide inhibited expression of stem-like markers, cell proliferation, and tumor growth synergistically in various models. Analysis of clinical datasets revealed a molecule pattern shift in different stages of prostate cancer, where we detected a significant correlation between AR and β-catenin expression. These data identify activation of the Wnt/β-catenin pathway as a major mechanism contributing to enzalutamide resistance and demonstrate the potential to stratify patients with high risk of said resistance.Significance: Wnt/β-catenin inhibition resensitizes prostate cancer cells to enzalutamide. Cancer Res; 78(12); 3147-62. ©2018 AACR.
Prospective evaluation of gadoxetic-acid MR for the non-invasive diagnosis of hepatocellular carcinoma in newly detected nodules &lt;=2 cm in cirrhotic patients
Authors: A. Forner, A. Darnell, C. Ayuso, J. Rimola, M.Á. García-Criado, R. Vilana, L. Bianchi, María Reig, J. Bruix
Journal: Journal of Hepatology (2018)
The direct comparison between 7th AJCC staging system and 8th AJCC staging system for prediction of survival with Korean multicenter HCC patients
Authors: Y-S. Lee, J.H. Kim, C.U. Lee, S.J. Suh, Y.K. Jung, Y.S. Seo, H.J. Yim, J.E. Yeon, K.S. Byun
Journal: Journal of Hepatology (2018)
Target volume delineation in locally advanced squamous cell carcinoma of the head and neck (SCCHN) using FDG-PET/CT images post-induction chemotherapy (IC).
Authors: Viktoras Rudzianskas, Elona Juozaityte, Milda Rudzianskiene, Severina Sediene, Rita Ambraziene, Saulius Vaitkus, Evaldas Padervinskis, Ilona Kulakiene
Journal: Journal of Clinical Oncology (2016)

e17519 Background: Current guidelines define that pre-IC target volumes must be used for radiotherapy (RT) planning. This prospective, phase II trial assessed the results of pts with SCCHN treatment with IC following by chemoradiotherapy (CRT), using post-IC PET/CT images for RT planning. Methods: Two PET/CT were performed: one prior IC, and one 2 weeks after 3 cycles of IC: docetaxel 75mg/m2, cisplatin 75mg/m2 and 5-FU 750 mg/m2 day 1-5. The gross tumor (GTVt) and nodal (GTVn) volumes on the post-IC PET/CT scans were contoured. The CTVt and CTVn were obtained by GTVt and GTVn plus 5 mm respectively. The elective CTV included CTVt, CTVn and bilateral elective lymphnodes. The margin of 3 mm was added to each CTV to create the PTVs. For PTVt and PTVn the prescribed doses were 70 Gy and 60 respectively, for PTVel – 50 Gy. CRT consisted of a chemotherapy with cisplatin (40 mg/m2 weekly) and RT (2 Gy once daily, 5 days a week). The primary end points was PFS. Secondary end points were OS and treatment safety. Acute toxicities were assessed using CTCAE v.4.0, late toxicities - using RTOG /EORTC criteria. Results: 47 pts with histologically confirmed SCCHN (oro- and hypopharyngeal), KPS 70% and intact organ function were included. The mean follow-up period was 17.2 (2-30.5) months. The mean OS was 25.3 months (95% CI, 22.5-28.1) and mean PFS was 23.2 months (95% CI, 20.3-26.1). The 2-years PFS and OS rate were 75% and 76%, respectively. The most common acute toxicities of grade 3-4 were febrile neutropenia 20%, leucopenia 26.7%, mucositis 37.8%. Late toxicities of grade 3 were: dysphagia 2.2% and xerostomia 8.9%. Conclusions: This study is promising for new target delineation strategies for SCCHN after IC. Further analysis is required to ascertain the influence of FDG-PET/CT in target delineation and main clinical outcomes. Clinical trial information: NCT02047201.
The first result from the general population hepatitis screening in Mongolia: 38% of 40-65 year olds screened and anti-HCV prevence of 15.6% among 40-65 year olds
Authors: B. Dashtseren, U. Baatarsuren, T. Dagvadorj, A. Bungert, Z. Genden, D. Yagaanbuyant, N. Dashdorj, N. Dashdorj
Journal: Journal of Hepatology (2018)
Remembering the man behind An Essay on the Shaking Palsy
Authors: Alastair Noyce
Journal: The Lancet Neurology (2018)

On Nov 16, 2017, a committed group of James Parkinson aficionados met for a historical walk at the Arnold Circus Bandstand, on the boundary between Bethnal Green and Shoreditch (London, UK), guided by retired local GP Dr Chris Derrett. The walk, followed by a lecture programme, was in celebration of the 200th anniversary of Parkinson's Essay on the Shaking Palsy, but by contrast with many of the other events held last year in his memory, this event was less about the disease that bears his name, and more about the man himself: the writer, the activist, the geologist, and the medic.
Response by Fernández-Jiménez et al to Letters Regarding Article, “Dynamic Edematous Response of the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial Area at Risk and Salvage”
Authors: Rodrigo Fernández-Jiménez, Ana Martin-García, Manuel Barreiro-Pérez, Javier Sánchez-González, Valentin Fuster, Pedro L. Sánchez, Borja Ibanez
Journal: Circulation (2018)
Evaluation of the new criteria in the diagnosis of cystic fibrosis liver disease
Authors: A. Alexopoulou, S. Pouriki, L. Vasilieva, T. Alexopoulos, F. Diamantea, M. Gioka, A. Nakou, D. Zampetas, I. Mani, S. Ntourakis
Journal: Journal of Hepatology (2018)
Acid Stimulation of the Citrate Transporter NaDC-1 Requires Pyk2 and ERK1/2 Signaling Pathways
Authors: Miriam Zacchia, Xuefei Tian, Enrica Zona, Robert J. Alpern, Patricia A. Preisig
Journal: Journal of the American Society of Nephrology (2018)

Background Urine citrate is reabsorbed exclusively along the renal proximal tubule via the apical Na + -dicarboxylate cotransporter NaDC-1. We previously showed that an acid load in vivo and media acidification in vitro increase NaDC-1 activity through endothelin-1 (ET-1)/endothelin B (ET B ) signaling. Here, we further examined the signaling pathway mediating acid-induced NaDC-1 activity. Methods We transiently transfected cultured opossum kidney cells, a model of the proximal tubule, with NaDC-1 and ET B and measured [ 14 C]-citrate uptake after media acidification under various experimental conditions, including inactivation of Pyk2 and c-Src, which were previously shown to be activated by media acidification. Wild-type (Pyk2 +/+ ) and Pyk2-null (Pyk2 −/− ) mice were exposed to NH 4 Cl loading and euthanized after various end points, at which time we harvested the kidneys for immunoblotting and brush border membrane NaDC-1 activity studies. Results Inhibition of Pyk2 or c-Src prevented acid stimulation but not ET-1 stimulation of NaDC-1 in vitro . Consistent with these results, NH 4 Cl loading stimulated NaDC-1 activity in kidneys of wild-type but not Pyk2 −/− mice. In cultured cells and in mice, ERK1/2 was rapidly phosphorylated by acid loading, even after Pyk2 knockdown, and it was required for acid but not ET-1/ET B stimulation of NaDC-1 in vitro . Media acidification also induced the phosphorylation of Raf1 and p90RSK, components of the ERK1/2 pathway, and inhibition of these proteins blocked acid stimulation of NaDC-1 activity. Conclusions Acid stimulation of NaDC-1 activity involves Pyk2/c-Src and Raf1-ERK1/2-p90RSK signaling pathways, but these pathways are not downstream of ET-1/ET B in this process.
During aging osteopontin deficiency increases vulnerability to non-alcoholic fatty liver disease progression and the associated extrahepatic metabolic complications
Authors: B.G. Santos, F. Gonzalez-Romero, M. Nunez-García, D.M. Congregado, D.S. de Urturi, V.G. de Juan, M.L. Martínez-Chantar, I. Aurrekoetxea, X. Buque, P. Aspichueta
Journal: Journal of Hepatology (2018)
Effect of combined farnesoid X receptor agonist (INT747) and dipeptidyl peptidase-4 inhibitor (sitagliptin) on liver fibrosis
Authors: N. Shimozato, T. Namisaki, T. Akahane, K. Moriya, M. Kitade, H. Kawaratani, K. Kaji, Y. Okura, H. Takaya, Y. Sawada, N. Nishimura, S. Sato, S. Saikawa, K. Seki, M. Furukawa, T. Kubo, H. Yoshiji
Journal: Journal of Hepatology (2018)
Risk of skin cancer in multiple myeloma patients: A retrospective cohort study.
Authors: Austin A Robinson, Alex Kitto, Simrin K Cheema, Erik K Madden, Adam S Norberg, Darron H Fors, Joseph W Diehl, Gabriel N. Waterman, James D. Hilger, Regina A. Swift, James R. Berenson
Journal: Journal of Clinical Oncology (2013)

e20044 Background: Multiple myeloma (MM) patients (pts) have shown a higher risk of developing other cancers, although the type, time course, and relationship to MM treatment of these cancers are less clear. In this study, we determined the risk of specific skin cancer (CA) types among MM patients and its relationship to onset of MM and treatment. Methods: MM pts and unrelated age, sex, and race-matched companions (controls) seen at a MM clinic were enrolled in a retrospective cohort study. Information regarding baseline characteristics of MM and history of skin CA was obtained from medical records. Overall skin CA prevalence and types were compared between groups; among MM patients, the occurrence of skin CA was analyzed relative to date of diagnosis and treatment regimens, with stratification according to treatment duration. Results: We enrolled 205 MM pts and 201 controls with 27.3% and 14.9% demonstrating skin CA, respectively (p &lt; 0.001). Specific types of skin CA included 60 and 37 basal cell carcinomas (BCC), 50 and 17 squamous cell carcinomas (SCC), and 9 and 5 melanomas in the MM pts and controls, respectively. The standardized incidence ratios (SIR) were SCC: 2.88 (p&lt; 0.001), BCC: 1.59 (p&lt;0.001), and melanoma: 1.76 (p = 0.074). SCC SIR was elevated (p&lt;0.001) across each yearly time point from 10 years prior to MM diagnosis through 10 years subsequent to MM diagnosis. BCC SIR was elevated (p &lt;0.002) from 7 through 10 years following MM diagnosis. The SIR markedly increased over time following the diagnosis of MM for both SCC and BCC. Relative risk (RR) was determined for pts treated with bortezomib, immunomodulatory agents, alkylating agents, glucocorticoids, and anthracyclines. There was no significant increase in RR overall or for any specific type of skin CA in relationship to the type or duration of MM treatment. Conclusions: MM pts show an increased risk of skin CA (there was no increase in melanoma incidence), including SCC and BCC. SCC occurred before and following the diagnosis of MM whereas BCC followed the diagnosis of MM. The post-MM diagnosis increase in skin CA was not related to specific drugs used to treat MM.
Falciform Ligament Artery Uptake on 99mTc MAA Planning Scan Before 90Y SIRT Confirmed by Retrospective SPECT/MRI Fusion
Authors: Nils Große Hokamp, Carsten Kobe, James K. O’Donnell, Amit Gupta
Journal: Clinical Nuclear Medicine (2018)

Selective internal radiation therapy using Y spheres is a treatment option for patients with primary or secondary liver cancer. To avoid complications, screening using Tc macroaggregated albumin is performed to identify lung shunting and extrahepatic depositions. For the latter, deposition after the anterior abdominal wall is frequently attributed to a patent falciform artery, although the vessel itself is rarely visible on SPECT/CT scans. We demonstrate that retrospective SPECT/MRI fusion clearly attributes the nuclide accumulation to a patent falciform artery. During selective internal radiation therapy, ice packs were placed on the anterior abdominal wall, resulting in a complication-free treatment.
Cycling Toward Progress: Ribociclib, a CDK 4/6 Inhibitor for Breast Cancer
Authors: Laura Spring, Aditya Bardia
Journal: Clinical Cancer Research (2018)

Ribociclib is an orally active, highly selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6. It is the second CDK 4/6 inhibitor approved for hormone receptor-positive breast cancer. The addition of ribociclib to an aromatase inhibitor has resulted in marked improvements in progression-free survival for patients with metastatic breast cancer. Clin Cancer Res; 24(13); 2981-3. ©2018 AACRSee related article by Shah et al., p. 2999.