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Favism and Glucose-6-Phosphate Dehydrogenase Deficiency.

N Engl J Med. 2018 Mar 15;378(11):1068


PMID: 29542311 [PubMed - indexed for MEDLINE]

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Favism and Glucose-6-Phosphate Dehydrogenase Deficiency.

N Engl J Med. 2018 Mar 15;378(11):1067-8

Authors: Winterbourn CC, Cheah FC

PMID: 29542310 [PubMed - indexed for MEDLINE]

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Favism and Glucose-6-Phosphate Dehydrogenase Deficiency.

N Engl J Med. 2018 03 15;378(11):1067

Authors: Zaidi AU, Callaghan MU, Ravindranath Y

PMID: 29542307 [PubMed - indexed for MEDLINE]

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CAR T-Cell Therapy in Large B-Cell Lymphoma.

N Engl J Med. 2018 Mar 15;378(11):1065

Authors: Quintás-Cardama A

PMID: 29542306 [PubMed - indexed for MEDLINE]

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Autologous Stem-Cell Transplantation for Severe Scleroderma.

N Engl J Med. 2018 Mar 15;378(11):1066

Authors: Shenoy P, Sreenath S, Aggarwal A

PMID: 29542305 [PubMed - indexed for MEDLINE]

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Autologous Stem-Cell Transplantation for Severe Scleroderma.

N Engl J Med. 2018 03 15;378(11):1066-1067


PMID: 29539292 [PubMed - indexed for MEDLINE]

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Recognizing the Global Impact of Zika Virus Infection during Pregnancy.

N Engl J Med. 2018 03 15;378(11):1055-1056

Authors: Honein MA

PMID: 29539290 [PubMed - indexed for MEDLINE]

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Favism and Glucose-6-Phosphate Dehydrogenase Deficiency.

N Engl J Med. 2018 03 15;378(11):1067-1069


PMID: 29539289 [PubMed - indexed for MEDLINE]

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A New Frontier in Curing Corneal Blindness.

N Engl J Med. 2018 03 15;378(11):1057-1058

Authors: Dana R

PMID: 29539278 [PubMed - indexed for MEDLINE]

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CAR T-Cell Therapy in Large B-Cell Lymphoma.

N Engl J Med. 2018 03 15;378(11):1065


PMID: 29539277 [PubMed - indexed for MEDLINE]

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Ever-Pregnant Female Blood Donors and Mortality Risk in Male Recipients-Reply.

JAMA. 2018 03 13;319(10):1049

Authors: Middelburg RA, Caram-Deelder C, van der Bom JG

PMID: 29536095 [PubMed - indexed for MEDLINE]

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Meta-analysis in Research on Nutrition-Reply.

JAMA. 2018 03 13;319(10):1050-1051

Authors: Barnard ND, Willett WC, Ding EL

PMID: 29536094 [PubMed - indexed for MEDLINE]

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ICU Admission and Mortality Among Elderly Adults-Reply.

JAMA. 2018 03 13;319(10):1047-1048

Authors: Guidet B, Pateron D, Boumendil A

PMID: 29536093 [PubMed - indexed for MEDLINE]

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Ever-Pregnant Female Blood Donors and Mortality Risk in Male Recipients.

JAMA. 2018 03 13;319(10):1048

Authors: Pocock SJ, Alonso AC

PMID: 29536092 [PubMed - indexed for MEDLINE]

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Ever-Pregnant Female Blood Donors and Mortality Risk in Male Recipients.

JAMA. 2018 03 13;319(10):1048-1049

Authors: Ali O, Wasfi MF, Uzoigwe CE

PMID: 29536091 [PubMed - indexed for MEDLINE]

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ICU Admission and Mortality Among Elderly Adults.

JAMA. 2018 03 13;319(10):1047

Authors: Andre V, Aissaoui N, Vincent F

PMID: 29536090 [PubMed - indexed for MEDLINE]

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Meta-analysis in Research on Nutrition.

JAMA. 2018 03 13;319(10):1050

Authors: Thornley S, Henderson G, Schofield G

PMID: 29536089 [PubMed - indexed for MEDLINE]

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Health Care Spending in the United States Compared With 10 Other High-Income Countries: What Uwe Reinhardt Might Have Said.

JAMA. 2018 03 13;319(10):990-992

Authors: Bauchner H, Fontanarosa PB

PMID: 29536083 [PubMed - indexed for MEDLINE]

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The Real Cost of the US Health Care System.

JAMA. 2018 03 13;319(10):983-985

Authors: Emanuel EJ

PMID: 29536081 [PubMed - indexed for MEDLINE]

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Factors Contributing to Higher Health Care Spending in the United States Compared With Other High-Income Countries.

JAMA. 2018 03 13;319(10):988-990

Authors: Parente ST

PMID: 29536080 [PubMed - indexed for MEDLINE]

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Case 37-2017: A Man with Unintentional Opioid Overdose.

N Engl J Med. 2018 03 01;378(9):873

Authors: Wakeman SE, Raja AS

PMID: 29490179 [PubMed - indexed for MEDLINE]

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Early Warning Systems for Hospitalized Pediatric Patients.

JAMA. 2018 03 13;319(10):981-982

Authors: Halpern NA

PMID: 29486492 [PubMed - indexed for MEDLINE]

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Double somatic mutations in mismatch repair genes are frequent in colorectal cancer after Hodgkin's lymphoma treatment.

Gut. 2018 03;67(3):447-455

Authors: Rigter LS, Snaebjornsson P, Rosenberg EH, Atmodimedjo PN, Aleman BM, Ten Hoeve J, Geurts-Giele WR, PALGA group, van Ravesteyn TW, Hoeksel J, Meijer GA, Te Riele H, van Leeuwen FE, Dinjens WN, van Leerdam ME

OBJECTIVE: Hodgkin's lymphoma survivors who were treated with infradiaphragmatic radiotherapy or procarbazine-containing chemotherapy have a fivefold increased risk of developing colorectal cancer (CRC). This study aims to provide insight into the development of therapy-related CRC (t-CRC) by evaluating histopathological and molecular characteristics.
DESIGN: 54 t-CRCs diagnosed in a Hodgkin's lymphoma survivor cohort were analysed for mismatch repair (MMR) proteins by immunohistochemistry, microsatellite instability (MSI) and KRAS/BRAF mutations. MSI t-CRCs were evaluated for promoter methylation and mutations in MMR genes. Pathogenicity of MMR gene mutations was evaluated by in silico predictions and functional analyses. Frequencies were compared with a general population cohort of CRC (n=1111).
RESULTS: KRAS and BRAF mutations were present in 41% and 15% t-CRCs, respectively. Compared with CRCs in the general population, t-CRCs had a higher MSI frequency (24% vs 11%, p=0.003) and more frequent loss of MSH2/MSH6 staining (13% vs 1%, p<0.001). Loss of MLH1/PMS2 staining and MLH1 promoter methylation were equally common in t-CRCs and the general population. In MSI CRCs without MLH1 promoter methylation, double somatic MMR gene mutations (or loss of heterozygosity as second hit) were detected in 7/10 (70%) t-CRCs and 8/36 (22%) CRCs in the general population (p=0.008). These MMR gene mutations in t-CRCs were classified as pathogenic. MSI t-CRC cases could not be ascribed to Lynch syndrome.
CONCLUSIONS: We have demonstrated a higher frequency of MSI among t-CRCs, which results from somatic MMR gene mutations. This suggests a novel association of somatic MMR gene mutations with prior anticancer treatment.

PMID: 29439113 [PubMed - indexed for MEDLINE]

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Management of patients on antithrombotic agents undergoing emergency and elective endoscopy: joint Asian Pacific Association of Gastroenterology (APAGE) and Asian Pacific Society for Digestive Endoscopy (APSDE) practice guidelines.

Gut. 2018 03;67(3):405-417

Authors: Chan FKL, Goh KL, Reddy N, Fujimoto K, Ho KY, Hokimoto S, Jeong YH, Kitazono T, Lee HS, Mahachai V, Tsoi KKF, Wu MS, Yan BP, Sugano K

This Guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society for Digestive Endoscopy (APSDE). It was developed in response to the increasing use of antithrombotic agents (antiplatelet agents and anticoagulants) in patients undergoing gastrointestinal (GI) endoscopy in Asia. After reviewing current practice guidelines in Europe and the USA, the joint committee identified unmet needs, noticed inconsistencies, raised doubts about certain recommendations and recognised significant discrepancies in clinical practice between different regions. We developed this joint official statement based on a systematic review of the literature, critical appraisal of existing guidelines and expert consensus using a two-stage modified Delphi process. This joint APAGE-APSDE Practice Guideline is intended to be an educational tool that assists clinicians in improving care for patients on antithrombotics who require emergency or elective GI endoscopy in the Asian Pacific region.

PMID: 29331946 [PubMed - indexed for MEDLINE]

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Adherent-invasive Escherichia coli in inflammatory bowel disease.

Gut. 2018 03;67(3):574-587

Authors: Palmela C, Chevarin C, Xu Z, Torres J, Sevrin G, Hirten R, Barnich N, Ng SC, Colombel JF

Intestinal microbiome dysbiosis has been consistently described in patients with IBD. In the last decades, Escherichia coli, and the adherent-invasive E coli (AIEC) pathotype in particular, has been implicated in the pathogenesis of IBD. Since the discovery of AIEC, two decades ago, progress has been made in unravelling these bacteria characteristics and its interaction with the gut immune system. The mechanisms of adhesion of AIEC to intestinal epithelial cells (via FimH and cell adhesion molecule 6) and its ability to escape autophagy when inside macrophages are reviewed here. We also explore the existing data on the prevalence of AIEC in patients with Crohn's disease and UC, and the association between the presence of AIEC and disease location, activity and postoperative recurrence. Finally, we highlight potential therapeutic strategies targeting AIEC colonisation of gut mucosa, including the use of phage therapy, bacteriocins and antiadhesive molecules. These strategies may open new avenues for the prevention and treatment of IBD in the future.

PMID: 29141957 [PubMed - indexed for MEDLINE]

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Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues.

Gut. 2018 03;67(3):521-533

Authors: Zhang M, Lykke-Andersen S, Zhu B, Xiao W, Hoskins JW, Zhang X, Rost LM, Collins I, Bunt MV, Jia J, Parikh H, Zhang T, Song L, Jermusyk A, Chung CC, Zhu B, Zhou W, Matters GL, Kurtz RC, Yeager M, Jensen TH, Brown KM, Ongen H, Bamlet WR, Murray BA, McCarthy MI, Chanock SJ, Chatterjee N, Wolpin BM, Smith JP, Olson SH, Petersen GM, Shi J, Amundadottir L

OBJECTIVE: To elucidate the genetic architecture of gene expression in pancreatic tissues.
DESIGN: We performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA sequencing and the corresponding 1000 genomes imputed germline genotypes. Data from pancreatic tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were included for comparison.
RESULTS: We identified 38 615 cis-eQTLs (in 484 genes) in histologically normal tissues and 39 713 cis-eQTL (in 237 genes) in tumour-derived tissues (false discovery rate <0.1), with the strongest effects seen near transcriptional start sites. Approximately 23% and 42% of genes with significant cis-eQTLs appeared to be specific for tumour-derived and normal-derived tissues, respectively. Significant enrichment of cis-eQTL variants was noted in non-coding regulatory regions, in particular for pancreatic tissues (1.53-fold to 3.12-fold, p≤0.0001), indicating tissue-specific functional relevance. A common pancreatic cancer risk locus on 9q34.2 (rs687289) was associated with ABO expression in histologically normal (p=5.8×10-8) and tumour-derived (p=8.3×10-5) tissues. The high linkage disequilibrium between this variant and the O blood group generating deletion variant in ABO (exon 6) suggested that nonsense-mediated decay (NMD) of the 'O' mRNA might explain this finding. However, knockdown of crucial NMD regulators did not influence decay of the ABO 'O' mRNA, indicating that a gene regulatory element influenced by pancreatic cancer risk alleles may underlie the eQTL.
CONCLUSIONS: We have identified cis-eQTLs representing potential functional regulatory variants in the pancreas and generated a rich data set for further studies on gene expression and its regulation in pancreatic tissues.

PMID: 28634199 [PubMed - indexed for MEDLINE]

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The effect of sustained virological response on the risk of extrahepatic manifestations of hepatitis C virus infection.

Gut. 2018 03;67(3):553-561

Authors: Mahale P, Engels EA, Li R, Torres HA, Hwang LY, Brown EL, Kramer JR

BACKGROUND AND AIM: Chronic HCV infection is associated with several extrahepatic manifestations (EHMs). Data on the effect of sustained virological response (SVR) on the risk of EHMs are limited.
METHODS: We conducted a retrospective cohort study using data of patients from the US Veterans Affairs HCV Clinical Case Registry who had a positive HCV RNA test (10/1999-08/2009). Patients receiving interferon-based antiviral therapy (AVT) were identified. SVR was defined as negative HCV RNA at least 12 weeks after end of AVT. Risks of eight incident EHMs were evaluated in Cox regression models.
RESULTS: Of the 160 875 HCV-infected veterans, 31 143 (19.4%) received AVT, of whom 10 575 (33.9%) experienced SVR. EHM risk was reduced in the SVR group compared with untreated patients for mixed cryoglobulinaemia (adjusted HR (aHR)=0.61; 95% CI 0.39 to 0.94), glomerulonephritis (aHR=0.62; 95% CI 0.48 to 0.79), porphyria cutanea tarda (PCT) (aHR=0.41; 95% CI 0.20 to 0.83), non-Hodgkin's lymphoma (NHL) (aHR=0.64; 95% CI 0.43 to 0.95), diabetes (aHR=0.82; 95% CI 0.76 to 0.88) and stroke (aHR=0.84; 95% CI 0.74 to 0.94), but not for lichen planus (aHR=1.11; 95% CI 0.78 to 1.56) or coronary heart disease (aHR=1.12; 95% CI 0.81 to 1.56). Risk reductions were also observed when patients with SVR were compared with treated patients without SVR for mixed cryoglobulinaemia, glomerulonephritis, PCT and diabetes. Significant reductions in the magnitude of aHRs towards the null with increasing time to initiation of AVT after HCV diagnosis were observed for glomerulonephritis, NHL and stroke.
CONCLUSIONS: Risks of several EHMs of HCV infection are reduced after AVT with SVR. However, early initiation of AVT may be required to reduce the risk of glomerulonephritis, NHL and stroke.

PMID: 28634198 [PubMed - indexed for MEDLINE]

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Proliferation of primary human hepatocytes and prevention of hepatitis B virus reinfection efficiently deplete nuclear cccDNA in vivo.

Gut. 2018 03;67(3):542-552

Authors: Allweiss L, Volz T, Giersch K, Kah J, Raffa G, Petersen J, Lohse AW, Beninati C, Pollicino T, Urban S, Lütgehetmann M, Dandri M

OBJECTIVE: The stability of the covalently closed circular DNA (cccDNA) in nuclei of non-dividing hepatocytes represents a key determinant of HBV persistence. Contrarily, studies with animal hepadnaviruses indicated that hepatocyte turnover can reduce cccDNA loads but knowledge on the proliferative capacity of HBV-infected primary human hepatocytes (PHHs) in vivo and the fate of cccDNA in dividing PHHs is still lacking. This study aimed to determine the impact of human hepatocyte division on cccDNA stability in vivo.
METHODS: PHH proliferation was triggered by serially transplanting hepatocytes from HBV-infected humanised mice into naïve recipients. Cell proliferation and virological changes were assessed by quantitative PCR, immunofluorescence and RNA in situ hybridisation. Viral integrations were analysed by gel separation and deep sequencing.
RESULTS: PHH proliferation strongly reduced all infection markers, including cccDNA (median 2.4 log/PHH). Remarkably, cell division appeared to cause cccDNA dilution among daughter cells and intrahepatic cccDNA loss. Nevertheless, HBV survived in sporadic non-proliferating human hepatocytes, so that virological markers rebounded as hepatocyte expansion relented. This was due to reinfection of quiescent PHHs since treatment with the entry inhibitor myrcludex-B or nucleoside analogues blocked viral spread and intrahepatic cccDNA accumulation. Viral integrations were detected both in donors and recipient mice but did not appear to contribute to antigen production.
CONCLUSIONS: We demonstrate that human hepatocyte division even without involvement of cytolytic mechanisms triggers substantial cccDNA loss. This process may be fundamental to resolve self-limiting acute infection and should be considered in future therapeutic interventions along with entry inhibition strategies.

PMID: 28428345 [PubMed - indexed for MEDLINE]

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In Reply-Electronic Health Records and Drugs Prescribed for Off-label Indications.

Mayo Clin Proc. 2017 04;92(4):684-685

Authors: Mackey TK, Liang BA

PMID: 28385205 [PubMed - indexed for MEDLINE]

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Electronic Health Records and Drugs Prescribed for Off-label Indications.

Mayo Clin Proc. 2017 04;92(4):683-684

Authors: Porter CB

PMID: 28385204 [PubMed - indexed for MEDLINE]

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In Reply-Atrial Fibrillation: Interatrial Block May Be an Underdiagnosed and Easily Recognizable Risk Factor.

Mayo Clin Proc. 2017 04;92(4):682

Authors: Morin DP, Bernard ML, Madias C, Rogers PA, Thihalolipavan S, Estes NA

PMID: 28385203 [PubMed - indexed for MEDLINE]

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Atrial Fibrillation: Interatrial Block May Be an Underdiagnosed and Easily Recognizable Risk Factor.

Mayo Clin Proc. 2017 04;92(4):681-682

Authors: Fernández-Fernández FJ

PMID: 28385202 [PubMed - indexed for MEDLINE]

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"Being Dumped" for Administrative Efficiency.

Mayo Clin Proc. 2017 04;92(4):681

Authors: Lichtstein DM, Cooper JM

PMID: 28385201 [PubMed - indexed for MEDLINE]

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Coronary Artery Disease: A Continuum, Not a Threshold.

Mayo Clin Proc. 2017 03;92(3):323-326

Authors: Rumberger JA

PMID: 28259224 [PubMed - indexed for MEDLINE]

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Effects of early physical exercise on later health - Authors' reply.

Lancet. 2017 02 25;389(10071):801

Authors: Ekelund U, Bauman A, Lee IM

PMID: 28248173 [PubMed - indexed for MEDLINE]

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Assessing robot-assisted laparoscopic prostatectomy.

Lancet. 2017 02 25;389(10071):800

Authors: Capogrosso P, Ventimiglia E, Salonia A

PMID: 28248171 [PubMed - indexed for MEDLINE]

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Assessing robot-assisted laparoscopic prostatectomy - Authors' reply.

Lancet. 2017 02 25;389(10071):800-801

Authors: Yaxley JW, Coughlin GD, Chambers SK, Dunglison N, Gardiner RA

PMID: 28248170 [PubMed - indexed for MEDLINE]

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Assessing robot-assisted laparoscopic prostatectomy.

Lancet. 2017 02 25;389(10071):799

Authors: Seisen T, Cole AP, Sun M, Kibel AS, Trinh QD

PMID: 28248169 [PubMed - indexed for MEDLINE]

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Assessing robot-assisted laparoscopic prostatectomy.

Lancet. 2017 02 25;389(10071):799

Authors: Arrabal-Polo MA, Arrabal-Martin M, Mijan-Ortiz JL, Vazquez-Alonso F, Cozar-Olmo JM

PMID: 28248168 [PubMed - indexed for MEDLINE]

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Telling the human story of Asia's invisible malaria burden.

Lancet. 2017 02 25;389(10071):781-782

Authors: Baird JK

PMID: 28248161 [PubMed - indexed for MEDLINE]

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Women, power, and the cancer divide.

Lancet. 2017 02 25;389(10071):773-774

Authors: Bachelet M

PMID: 28248158 [PubMed - indexed for MEDLINE]

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Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis.

Gut. 2018 03;67(3):430-440

Authors: Eusebi LH, Ratnakumaran R, Yuan Y, Solaymani-Dodaran M, Bazzoli F, Ford AC

OBJECTIVES: Gastro-oesophageal reflux symptoms are common in the community, but there has been no definitive systematic review and meta-analysis of data from all studies to estimate their global prevalence, or potential risk factors for them.
DESIGN: Medline, Embase and Embase Classic were searched (until September 2016) to identify population-based studies that reported the prevalence of gastro-oesophageal reflux symptoms in adults (≥15 years); gastro-oesophageal reflux was defined using symptom-based criteria or questionnaires. The prevalence was extracted for all studies, and according to the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, OR and 95% CIs were calculated.
RESULTS: Of the 14 132 citations evaluated, 102 reported the prevalence of gastro-oesophageal reflux symptoms in 108 separate study populations, containing 460 984 subjects. Prevalence varied according to country (from 2.5% in China to 51.2% in Greece) and criteria used to define gastro-oesophageal reflux symptoms. When only studies using a weekly frequency of heart burn or regurgitation to define presence were considered, pooled prevalence was 13.3% (95% CI 12.0% to 14.6%). Prevalence was higher in subjects ≥50 years (OR 1.32; 95% CI 1.12 to 1.54), smokers (OR 1.26; 95% CI 1.04 to 1.52), non-steroidal anti-inflammatory drug (NSAID)/aspirin users (OR 1.44; 95% CI 1.10 to 1.88) and obese individuals (OR 1.73; 95% CI 1.46 to 2.06).
CONCLUSIONS: The prevalence of gastro-oesophageal reflux symptoms varied strikingly among countries, even when similar definitions were used to define their presence. Prevalence was significantly higher in subjects ≥50 years, smokers, NSAID users and obese individuals, although these associations were modest.

PMID: 28232473 [PubMed - indexed for MEDLINE]

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Green space is important for health.

Lancet. 2017 02 18;389(10070):700

Authors: Nieuwenhuijsen M, Khreis H

PMID: 28229878 [PubMed - indexed for MEDLINE]

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Funding agency mechanisms to increase sex and gender analysis.

Lancet. 2017 02 18;389(10070):699

Authors: Duchesne A, Tannenbaum C, Einstein G

PMID: 28229876 [PubMed - indexed for MEDLINE]

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Progress and challenges to introduce midwifery education in Nepal.

Lancet. 2017 02 18;389(10070):698-699

Authors: Goyet S, Tamang L, Alvarez VB, Shrestha ID, Bajracharya K

PMID: 28229873 [PubMed - indexed for MEDLINE]

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Setting maternal mortality targets for the SDGs.

Lancet. 2017 02 18;389(10070):696-697

Authors: Boldosser-Boesch A, Brun M, Carvajal L, Chou D, de Bernis L, Fogg K, Hill K, Jolivet R, McCallon B, Moran A, Say L, Smith J, Stanton ME, Ten Hoope-Bender P, Wegner MN, Ending Preventable Maternal Mortality working group

PMID: 28229871 [PubMed - indexed for MEDLINE]

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Early goal-directed mobilisation after surgery.

Lancet. 2017 02 18;389(10070):695

Authors: Li G

PMID: 28229870 [PubMed - indexed for MEDLINE]

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Early goal-directed mobilisation after surgery.

Lancet. 2017 02 18;389(10070):695

Authors: Tada A, Ozaki A, Kuwano K, Morita T, Tanimoto T

PMID: 28229869 [PubMed - indexed for MEDLINE]

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Early goal-directed mobilisation after surgery - Authors' reply.

Lancet. 2017 02 18;389(10070):695-696

Authors: Eikermann M, Schaller SJ, Kasotakis G, Anstey M, Houle T

PMID: 28229868 [PubMed - indexed for MEDLINE]

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Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy.

Gut. 2018 03;67(3):534-541

Authors: Tang R, Wei Y, Li Y, Chen W, Chen H, Wang Q, Yang F, Miao Q, Xiao X, Zhang H, Lian M, Jiang X, Zhang J, Cao Q, Fan Z, Wu M, Qiu D, Fang JY, Ansari A, Gershwin ME, Ma X

OBJECTIVE: A close relationship between gut microbiota and some chronic liver disorders has recently been described. Herein, we systematically performed a comparative analysis of the gut microbiome in primary biliary cholangitis (PBC) and healthy controls.
DESIGN: We first conducted a cross-sectional study of 60 ursodeoxycholic acid (UDCA) treatment-naïve patients with PBC and 80 matched healthy controls. Second, an independent cohort composed of 19 treatment-naïve patients and 34 controls was used to validate the results. Finally, a prospective study was performed in a subgroup of 37 patients with PBC who underwent analysis before and after 6 months of UDCA treatment. Faecal samples were collected, and microbiomes were analysed by 16S ribosomal RNA gene sequencing.
RESULTS: A significant reduction of within-individual microbial diversity was noted in PBC (p=0.03). A signature defined by decreased abundance of four genera and increased abundance of eight genera strongly correlated with PBC (area under curve=0.86, 0.84 in exploration and validation data, respectively). Notably, the abundance of six PBC-associated genera was reversed after 6 months of UDCA treatment. In particular, Faecalibacterium, enriched in controls, was further decreased in gp210-positive than gp210-negative patients (p=0.002). Of interest was the finding that the increased capacity for the inferred pathway, bacterial invasion of epithelial cells in PBC, highly correlated with the abundance of bacteria belonging to Enterobacteriaceae.
CONCLUSIONS: This study presents a comprehensive landscape of gut microbiota in PBC. Dysbiosis was found in the gut microbiome in PBC and partially relieved by UDCA. Our study suggests that gut microbiota is a potential therapeutic target and diagnostic biomarker for PBC.

PMID: 28213609 [PubMed - indexed for MEDLINE]

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Polypoid lesions from the oesophagus to colon.

Gut. 2018 03;67(3):552

Authors: Huang PJ, Chang CL, Suk FM

PMID: 28174200 [PubMed - indexed for MEDLINE]

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Selling smoking cessation.

Lancet. 2017 02 25;389(10071):768-770

Authors: Cummings KM, Carpenter MJ

PMID: 28129988 [PubMed - indexed for MEDLINE]

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Diagnostic accuracy of multi-parametric MRI and transrectal ultrasound-guided biopsy in prostate cancer.

Lancet. 2017 02 25;389(10071):767-768

Authors: Thompson JE, Stricker PD

PMID: 28126331 [PubMed - indexed for MEDLINE]

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Laryngeal mask airways in anaesthetised infants: a paradigm shift?

Lancet. 2017 02 18;389(10070):673-674

Authors: Fiadjoe J, Litman R

PMID: 28108039 [PubMed - indexed for MEDLINE]

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Terminal room disinfection: how much BETR can it get?

Lancet. 2017 02 25;389(10071):765-766

Authors: Crotty MP, Jackson PJ

PMID: 28104286 [PubMed - indexed for MEDLINE]

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Stressed brain, stressed heart?

Lancet. 2017 02 25;389(10071):770-771

Authors: Bot I, Kuiper J

PMID: 28088337 [PubMed - indexed for MEDLINE]

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Clinical development of hepatitis C virus host-targeting agents.

Lancet. 2017 02 18;389(10070):674-675

Authors: Zeisel MB, Baumert TF

PMID: 28087068 [PubMed - indexed for MEDLINE]

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Fibroblast drug scavenging increases intratumoural gemcitabine accumulation in murine pancreas cancer.

Gut. 2018 03;67(3):497-507

Authors: Hessmann E, Patzak MS, Klein L, Chen N, Kari V, Ramu I, Bapiro TE, Frese KK, Gopinathan A, Richards FM, Jodrell DI, Verbeke C, Li X, Heuchel R, Löhr JM, Johnsen SA, Gress TM, Ellenrieder V, Neesse A

OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery.
DESIGN: Gemcitabine metabolites were analysed in LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry. Functional and preclinical experiments, as well as expression analysis of stromal markers and gemcitabine metabolism pathways were performed in murine and human specimen to investigate the preclinical implications and the mechanism of gemcitabine accumulation.
RESULTS: Gemcitabine accumulation was significantly enhanced in fibroblast-rich tumours compared with liver metastases and normal liver. In vitro, significantly increased concentrations of activated 2',2'-difluorodeoxycytidine-5'-triphosphate (dFdCTP) and greatly reduced amounts of the inactive gemcitabine metabolite 2',2'-difluorodeoxyuridine were detected in PSCs and CAFs. Mechanistically, key metabolic enzymes involved in gemcitabine inactivation such as hydrolytic cytosolic 5'-nucleotidases (Nt5c1A, Nt5c3) were expressed at low levels in CAFs in vitro and in vivo, and recombinant expression of Nt5c1A resulted in decreased intracellular dFdCTP concentrations in vitro. Moreover, gemcitabine treatment in KPC mice reduced the number of liver metastases by >50%.
CONCLUSIONS: Our findings suggest that fibroblast drug scavenging may contribute to the clinical failure of gemcitabine in desmoplastic PDAC. Metabolic targeting of CAFs may thus be a promising strategy to enhance the antiproliferative effects of gemcitabine.

PMID: 28077438 [PubMed - indexed for MEDLINE]

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Pancreatic cancer cell lines as patient-derived avatars: genetic characterisation and functional utility.

Gut. 2018 03;67(3):508-520

Authors: Knudsen ES, Balaji U, Mannakee B, Vail P, Eslinger C, Moxom C, Mansour J, Witkiewicz AK

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a therapy recalcitrant disease with the worst survival rate of common solid tumours. Preclinical models that accurately reflect the genetic and biological diversity of PDAC will be important for delineating features of tumour biology and therapeutic vulnerabilities.
DESIGN: 27 primary PDAC tumours were employed for genetic analysis and development of tumour models. Tumour tissue was used for derivation of xenografts and cell lines. Exome sequencing was performed on the originating tumour and developed models. RNA sequencing, histological and functional analyses were employed to determine the relationship of the patient-derived models to clinical presentation of PDAC.
RESULTS: The cohort employed captured the genetic diversity of PDAC. From most cases, both cell lines and xenograft models were developed. Exome sequencing confirmed preservation of the primary tumour mutations in developed cell lines, which remained stable with extended passaging. The level of genetic conservation in the cell lines was comparable to that observed with patient-derived xenograft (PDX) models. Unlike historically established PDAC cancer cell lines, patient-derived models recapitulated the histological architecture of the primary tumour and exhibited metastatic spread similar to that observed clinically. Detailed genetic analyses of tumours and derived models revealed features of ex vivo evolution and the clonal architecture of PDAC. Functional analysis was used to elucidate therapeutic vulnerabilities of relevance to treatment of PDAC.
CONCLUSIONS: These data illustrate that with the appropriate methods it is possible to develop cell lines that maintain genetic features of PDAC. Such models serve as important substrates for analysing the significance of genetic variants and create a unique biorepository of annotated cell lines and xenografts that were established simultaneously from same primary tumour. These models can be used to infer genetic and empirically determined therapeutic sensitivities that would be germane to the patient.

PMID: 28073890 [PubMed - indexed for MEDLINE]

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Meat intake and risk of diverticulitis among men.

Gut. 2018 03;67(3):466-472

Authors: Cao Y, Strate LL, Keeley BR, Tam I, Wu K, Giovannucci EL, Chan AT

OBJECTIVE: Diverticulitis is a common disease with a substantial clinical and economic burden. Besides dietary fibre, the role of other foods in the prevention of diverticulitis is underexplored.
DESIGN: We prospectively examined the association between consumption of meat (total red meat, red unprocessed meat, red processed meat, poultry and fish) with risk of incident diverticulitis among 46 461 men enrolled in the Health Professionals Follow-Up Study (1986-2012). Cox proportional hazards models were used to compute relative risks (RRs) and 95% CIs.
RESULTS: During 651 970 person-years of follow-up, we documented 764 cases of incident diverticulitis. Compared with men in the lowest quintile (Q1) of total red meat consumption, men in the highest quintile (Q5) had a multivariable RR of 1.58 (95% CI 1.19 to 2.11; p for trend=0.01). The increase in risk was non-linear, plateauing after six servings per week (p for non-linearity=0.002). The association was stronger for unprocessed red meat (RR for Q5 vs Q1: 1.51; 95% CI 1.12 to 2.03; p for trend=0.03) than for processed red meat (RR for Q5 vs Q1: 1.03; 95% CI 0.78 to 1.35; p for trend=0.26). Higher consumption of poultry or fish was not associated with risk of diverticulitis. However, the substitution of poultry or fish for one serving of unprocessed red meat per day was associated with a decrease in risk of diverticulitis (multivariable RR 0.80; 95% CI 0.63 to 0.99).
CONCLUSIONS: Red meat intake, particularly unprocessed red meat, was associated with an increased risk of diverticulitis. The findings provide practical dietary guidance for patients at risk of diverticulitis.

PMID: 28069830 [PubMed - indexed for MEDLINE]

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Sense and sensitivity: incompatible patients and their donors in kidney transplantation.

Lancet. 2017 02 18;389(10070):677-678

Authors: Reese PP, Mohan S

PMID: 28065560 [PubMed - indexed for MEDLINE]

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Living close to heavy traffic roads, air pollution, and dementia.

Lancet. 2017 02 18;389(10070):675-677

Authors: Calderón-Garcidueñas L, Villarreal-Ríos R

PMID: 28063596 [PubMed - indexed for MEDLINE]

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Cancer incidence and mortality risks in a large US Barrett's oesophagus cohort.

Gut. 2018 03;67(3):418-529

Authors: Cook MB, Coburn SB, Lam JR, Taylor PR, Schneider JL, Corley DA

OBJECTIVE: Barrett's oesophagus (BE) increases the risk of oesophageal adenocarcinoma by 10-55 times that of the general population, but no community-based cancer-specific incidence and cause-specific mortality risk estimates exist for large cohorts in the USA.
DESIGN: Within Kaiser Permanente Northern California (KPNC), we identified patients with BE diagnosed during 1995-2012. KPNC cancer registry and mortality files were used to estimate standardised incidence ratios (SIR), standardised mortality ratios (SMR) and excess absolute risks.
RESULTS: There were 8929 patients with BE providing 50 147 person-years of follow-up. Compared with the greater KPNC population, patients with BE had increased risks of any cancer (SIR=1.40, 95% CI 1.31 to 1.49), which slightly decreased after excluding oesophageal cancer. Oesophageal adenocarcinoma risk was increased 24 times, which translated into an excess absolute risk of 24 cases per 10 000 person-years. Although oesophageal adenocarcinoma risk decreased with time since BE diagnosis, oesophageal cancer mortality did not, indicating that the true risk is stable and persistent with time. Relative risks of cardia and stomach cancers were increased, but excess absolute risks were modest. Risks of colorectal, lung and prostate cancers were unaltered. All-cause mortality was slightly increased after excluding oesophageal cancer (SMR=1.24, 95% CI 1.18 to 1.31), but time-stratified analyses indicated that this was likely attributable to diagnostic bias. Cause-specific SMRs were elevated for ischaemic heart disease (SMR=1.39, 95% CI 1.18 to 1.63), respiratory system diseases (SMR=1.51, 95% CI 1.29 to 1.75) and digestive system diseases (SMR=2.20 95% CI 1.75 to 2.75).
CONCLUSIONS: Patients with BE had a persistent excess risk of oesophageal adenocarcinoma over time, although their absolute excess risks for this cancer, any cancer and overall mortality were modest.

PMID: 28053055 [PubMed - indexed for MEDLINE]

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A comparative effectiveness trial of two faecal immunochemical tests for haemoglobin (FIT). Assessment of test performance and adherence in a single round of a population-based screening programme for colorectal cancer.

Gut. 2018 03;67(3):485-496

Authors: Passamonti B, Malaspina M, Fraser CG, Tintori B, Carlani A, D'Angelo V, Galeazzi P, Di Dato E, Mariotti L, Bulletti S, D'Amico MR, Gustinucci D, Martinelli N, Spita N, Cesarini E, Rubeca T, Giaimo M, Segnan N, Senore C

AIM: To compare acceptability and diagnostic accuracy of a recently available faecal immunochemical test (FIT) system (HM-JACKarc) with the FIT routinely used in an established screening programme (OC-Sensor).
DESIGN: Randomised controlled trial (ISRCTN20086618) within a population-based colorectal cancer (CRC) screening programme. Subjects eligible for invitation in the Umbria Region (Italy) programme were randomised (ratio 1:1) to be screened using one of the FIT systems.
RESULTS: Screening uptake among the 48 888 invitees was the same for both systems among subjects invited in the first round and higher with OC-Sensor than with HM-JACKarc (relative risk (RR): 1.03; 95% CI 1.02 to 1.04) among those invited in subsequent rounds. Positivity rate (PR) was similar with OC-Sensor (6.5%) as with HM-JACKarc (6.2%) among subjects performing their first FIT screening and higher with OC-Sensor (5.6%, RR: 1.25, 95% CI 1.12 to 1.40) than with HM-JACKarc (4.4%) among those screened in previous rounds. Positive predictive value (PPV) (OC-Sensor: 25.9%, HM-JACKarc: 25.6%) and detection rate (DR) (OC-Sensor: 1.40%; HM-JACKarc: 1.42%) for advanced neoplasia (AN: CRC + advanced adenoma) were similar among subjects performing their first FIT screening. The differences in the AN PPV (OC-Sensor: 20.3%, HM-JACKarc: 22.6%) and DR (OC-Sensor: 0.96%, HM-JACKarc: 0.83%) among those screened in previous rounds were not statistically significant. The number needed to scope to detect one AN was 3.9 (95% CI 5.8 to 2.9) and 3.9 (95% CI 5.5 to 2.9) at first and 4.9 (95% CI 5.8 to 4.2) and 4.4 (95% CI 5.3 to 3.7) at subsequent screening, with OC-Sensor and HM-JACKarc, respectively.
CONCLUSIONS: Our results suggest that acceptability and diagnostic performance of HM-JACKarc and of OC-Sensor systems are similar in a screening setting.

PMID: 27974550 [PubMed - indexed for MEDLINE]

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Development of a Microscopic Colitis Disease Activity Index: a prospective cohort study.

Gut. 2018 03;67(3):441-446

Authors: Cotter TG, Binder M, Loftus EV, Abboud R, McNally MA, Smyrk TC, Tremaine WJ, Sandborn WJ, Pardi DS

OBJECTIVE: Microscopic colitis (MC) is a common cause of chronic diarrhoea, often with additional symptoms. No validated instruments exist to assess disease activity in MC, making it difficult to compare efficacy of treatments between clinical trials. We aimed to identify clinical features that independently predicted disease severity and create a Microscopic Colitis Disease Activity Index (MCDAI).
DESIGN: Patients with MC were prospectively administered a survey assessing their GI symptoms and the IBD Questionnaire (IBDQ). A single investigator also scored a physician global assessment (PGA) of disease severity on a 10-point scale. Multiple linear regression identified which symptoms best predicted the PGA. These symptoms were then combined in a weighted formula to create the MCDAI. The relationship between MCDAI and the IBDQ was investigated.
RESULTS: Of the 175 patients enrolled, 13 (7.4%) did not complete the survey. The remaining 162 had a median age of 66 years (range, 57-73) and 74% were female. Several clinical features were independently associated with PGA (number of unformed stools daily, presence of nocturnal stools, abdominal pain, weight loss, faecal urgency and faecal incontinence). These parameters were combined to create the MCDAI, which strongly predicted the PGA (R2=0.80). A 1-unit decrease in disease activity (ΔMCDAI) was associated with a 9-unit increase in quality of life (ΔIBDQ).
CONCLUSIONS: The MCDAI strongly predicted the PGA and correlated with a validated measure of quality of life. Several symptoms in addition to diarrhoea are associated with disease severity in MC.

PMID: 27965284 [PubMed - indexed for MEDLINE]

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Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer.

Gut. 2018 03;67(3):562-573

Authors: Samson A, Bentham MJ, Scott K, Nuovo G, Bloy A, Appleton E, Adair RA, Dave R, Peckham-Cooper A, Toogood G, Nagamori S, Coffey M, Vile R, Harrington K, Selby P, Errington-Mais F, Melcher A, Griffin S

OBJECTIVE: Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer.
DESIGN AND RESULTS: Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity and independently of viral genome replication. As well as achieving therapy in preclinical models of HCC through the activation of innate degranulating immune cells, Reo-induced cytokine responses efficiently suppressed HCV replication both in vitro and in vivo. Furthermore, Reo-induced innate responses were also effective against models of HBV-associated HCC, as well as an alternative endogenous model of Epstein-Barr virus-associated lymphoma. Interestingly, Reo appeared superior to the majority of OVs in its ability to elicit innate inflammatory responses from primary liver tissue.
CONCLUSIONS: We propose that Reo and other select proinflammatory OV may be used in the treatment of multiple cancers associated with oncogenic virus infections, simultaneously reducing both virus-associated oncogenic drive and tumour burden. In the case of HCV-associated HCC (HCV-HCC), Reo should be considered as an alternative agent to supplement and support current HCV-HCC therapies, particularly in those countries where access to new HCV antiviral treatments may be limited.

PMID: 27902444 [PubMed - indexed for MEDLINE]

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Modifiable lifestyle factors associated with risk of sessile serrated polyps, conventional adenomas and hyperplastic polyps.

Gut. 2018 03;67(3):456-465

Authors: Davenport JR, Su T, Zhao Z, Coleman HG, Smalley WE, Ness RM, Zheng W, Shrubsole MJ

OBJECTIVE: To identify modifiable factors associated with sessile serrated polyps (SSPs) and compare the association of these factors with conventional adenomas (ADs) and hyperplastic polyps (HPs).
DESIGN: We used data from the Tennessee Colorectal Polyp Study, a colonoscopy-based case-control study. Included were 214 SSP cases, 1779 AD cases, 560 HP cases and 3851 polyp-free controls.
RESULTS: Cigarette smoking was associated with increased risk for all polyps and was stronger for SSPs than for ADs (OR 1.74, 95% CI 1.16 to 2.62, for current vs never, ptrend=0.008). Current regular use of non-steroidal anti-inflammatory drugs was associated with a 40% reduction in SSP risk in comparison with never users (OR 0.68, 95% CI 0.48 to 0.96, ptrend=0.03), similar to the association with AD. Red meat intake was strongly associated with SSP risk (OR 2.59, 95% CI 1.41 to 4.74 for highest vs lowest intake, ptrend<0.001) and the association with SSP was stronger than with AD (ptrend=0.003). Obesity, folate intake, fibre intake and fat intake were not associated with SSP risk after adjustment for other factors. Exercise, alcohol use and calcium intake were not associated with risk for SSPs.
CONCLUSIONS: SSPs share some modifiable risk factors for ADs, some of which are more strongly associated with SSPs than ADs. Thus, preventive efforts to reduce risk for ADs may also be applicable to SSPs. Additionally, SSPs have some distinctive risk factors. Future studies should evaluate the preventive strategies for these factors. The findings from this study also contribute to an understanding of the aetiology and biology of SSPs.

PMID: 27852795 [PubMed - indexed for MEDLINE]

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Protein and glycomic plasma markers for early detection of adenoma and colon cancer.

Gut. 2018 03;67(3):473-484

Authors: Rho JH, Ladd JJ, Li CI, Potter JD, Zhang Y, Shelley D, Shibata D, Coppola D, Yamada H, Toyoda H, Tada T, Kumada T, Brenner DE, Hanash SM, Lampe PD

OBJECTIVE: To discover and confirm blood-based colon cancer early-detection markers.
DESIGN: We created a high-density antibody microarray to detect differences in protein levels in plasma from individuals diagnosed with colon cancer <3 years after blood was drawn (ie, prediagnostic) and cancer-free, matched controls. Potential markers were tested on plasma samples from people diagnosed with adenoma or cancer, compared with controls. Components of an optimal 5-marker panel were tested via immunoblotting using a third sample set, Luminex assay in a large fourth sample set and immunohistochemistry (IHC) on tissue microarrays.
RESULTS: In the prediagnostic samples, we found 78 significantly (t-test) increased proteins, 32 of which were confirmed in the diagnostic samples. From these 32, optimal 4-marker panels of BAG family molecular chaperone regulator 4 (BAG4), interleukin-6 receptor subunit beta (IL6ST), von Willebrand factor (VWF) and CD44 or epidermal growth factor receptor (EGFR) were established. Each panel member and the panels also showed increases in the diagnostic adenoma and cancer samples in independent third and fourth sample sets via immunoblot and Luminex, respectively. IHC results showed increased levels of BAG4, IL6ST and CD44 in adenoma and cancer tissues. Inclusion of EGFR and CD44 sialyl Lewis-A and Lewis-X content increased the panel performance. The protein/glycoprotein panel was statistically significantly higher in colon cancer samples, characterised by a range of area under the curves from 0.90 (95% CI 0.82 to 0.98) to 0.86 (95% CI 0.83 to 0.88), for the larger second and fourth sets, respectively.
CONCLUSIONS: A panel including BAG4, IL6ST, VWF, EGFR and CD44 protein/glycomics performed well for detection of early stages of colon cancer and should be further examined in larger studies.

PMID: 27821646 [PubMed - indexed for MEDLINE]

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Women's cancers: shining a light on a neglected health inequity.

Lancet. 2017 02 25;389(10071):771-773

Authors: Samarasekera U, Horton R

PMID: 27814968 [PubMed - indexed for MEDLINE]

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Origin of Multiple Formula Use to Calculate Intraocular Lens Power-Reply.

JAMA Ophthalmol. 2016 07 01;134(7):848-9

Authors: Ladas JG, Jun AS, Devgan U

PMID: 27259075 [PubMed - indexed for MEDLINE]

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Origin of Multiple Formula Use to Calculate Intraocular Lens Power-Reply.

JAMA Ophthalmol. 2016 07 01;134(7):848

Authors: Hee MR

PMID: 27258936 [PubMed - indexed for MEDLINE]

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Update on Screening Recommendations for Hydroxychloroquine Retinopathy.

JAMA Ophthalmol. 2016 07 01;134(7):849

Authors: Kim JE, Marmor MF

PMID: 27258704 [PubMed - indexed for MEDLINE]

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Origin of Multiple Formula Use to Calculate Intraocular Lens Power.

JAMA Ophthalmol. 2016 07 01;134(7):847-8

Authors: Hoffer KJ

PMID: 27258599 [PubMed - indexed for MEDLINE]

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Subconcussive Head Trauma and Near Point of Convergence.

JAMA Ophthalmol. 2016 07 01;134(7):770-1

Authors: Lee AG, Galetta SL

PMID: 27258455 [PubMed - indexed for MEDLINE]

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UV-A Protection From Auto Glass, Cataracts, and the Ophthalmologist.

JAMA Ophthalmol. 2016 07 01;134(7):776-7

Authors: Weiss JS

PMID: 27258328 [PubMed - indexed for MEDLINE]

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New Understanding of Age-Related Macular Degeneration Through Quantitative Autofluorescence.

JAMA Ophthalmol. 2016 07 01;134(7):824-6

Authors: Smith RT

PMID: 27254789 [PubMed - indexed for MEDLINE]

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Influence of Managed Care on the Variation in Rate and Timing of Cataract Surgery-Reply.

JAMA Ophthalmol. 2016 07 01;134(7):847

Authors: Stein JD, Lee PP

PMID: 27228033 [PubMed - indexed for MEDLINE]

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Influence of Managed Care on the Variation in Rate and Timing of Cataract Surgery.

JAMA Ophthalmol. 2016 07 01;134(7):846-7

Authors: French DD, Margo CE, Greenberg PB

PMID: 27227660 [PubMed - indexed for MEDLINE]

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Axenfeld Loop vs Extrasclerally Extending Ciliary Body Tumor.

JAMA Ophthalmol. 2016 07 01;134(7):846

Authors: Burris CK

PMID: 27149440 [PubMed - indexed for MEDLINE]

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Axenfeld Loop vs Extrasclerally Extending Ciliary Body Tumor-Reply.

JAMA Ophthalmol. 2016 07 01;134(7):846

Authors: Koch KR, Heindl LM

PMID: 27148670 [PubMed - indexed for MEDLINE]

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Prognostication of Uveal Melanoma: A Work in Progress.

JAMA Ophthalmol. 2016 07 01;134(7):740-1

Authors: Singh AD

PMID: 27124594 [PubMed - indexed for MEDLINE]

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Development, Use, and Interpretation of Patient-Reported Outcomes for Clinical Decision Making in Ophthalmology.

JAMA Ophthalmol. 2016 06 01;134(6):690-2

Authors: Miskala PH

PMID: 27124484 [PubMed - indexed for MEDLINE]

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Panretinal Photocoagulation vs Anti-Vascular Endothelial Growth Factor for Proliferative Diabetic Retinopathy-Reply.

JAMA Ophthalmol. 2016 06 01;134(6):716

Authors: Gross JG, Glassman AR

PMID: 27101313 [PubMed - indexed for MEDLINE]

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Panretinal Photocoagulation vs Anti-Vascular Endothelial Growth Factor for Proliferative Diabetic Retinopathy.

JAMA Ophthalmol. 2016 06 01;134(6):715-6

Authors: Singh SR, Singh R

PMID: 27101156 [PubMed - indexed for MEDLINE]

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Genetics and the Variable Phenotype of Age-Related Macular Degeneration.

JAMA Ophthalmol. 2016 06 01;134(6):681-2

Authors: Chowers I

PMID: 27101020 [PubMed - indexed for MEDLINE]

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Driving Eligibility in Proliferative Diabetic Retinopathy.

JAMA Ophthalmol. 2016 06 01;134(6):672-3

Authors: Owsley C, McGwin G

PMID: 27078817 [PubMed - indexed for MEDLINE]

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Enhancing the Value of Preschool Vision Screenings.

JAMA Ophthalmol. 2016 06 01;134(6):664-5

Authors: Ross EL, Stein JD

PMID: 27077370 [PubMed - indexed for MEDLINE]

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Further Evidence That Cataract Surgery Is Not Associated With Macular Degeneration Progression.

JAMA Ophthalmol. 2016 06 01;134(6):627

Authors: Paulus YM, Johnson MW

PMID: 27031237 [PubMed - indexed for MEDLINE]

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A breakthrough by Australian scientists has brought the introduction of an unlikely hero in the global fight against antibiotic resistance a step closer; the humble platypus.
Bread features heavily in many diets worldwide, and is one of the biggest sources of salt in diets. A new survey has revealed shocking levels of salt present in this essential staple.
Experts aim to halve the number of deaths from a type of meningitis by changing drug treatment as a result of a new medical study. The fungal infection cryptococcal meningitis is responsible for more than 180,000 deaths per year worldwide, mainly in HIV-infected patients. Current treatment for this type of meningitis is difficult and mortality rates in Africa in routine care are in the region of 70% - as high as for the Ebola virus infection. Under the new suggested treatment regimen, the research indicates this would fall to 25-35% - potentially saving up to 80,000 lives a year.
The process we call learning is in fact a well-orchestrated symphony of thousands of molecular reactions, but the exact interplay between these reactions remains largely unknown. Now, researchers have modeled the molecular basis of learning in the cerebellum, a part of the brain that receives sensory input and coordinates voluntary movements.
A new study shows that a high percentage of military personnel with sleep disturbances met criteria for nightmare disorder, but few of them reported nightmares as a reason for sleep evaluation. Those with nightmare disorder had an increased risk of other sleep and mental health disorders.
Blacks often have higher exposures to air pollutants than whites, elevating their risk for developing heart disease and death. Air pollution is associated with elevated blood sugar, blood vessel dysfunction, heart disease and death.
Coffee affects your metabolism in dozens of other ways besides waking you up, including your metabolism of neurotransmitters typically linked to cannabis, a study reports. The neurotransmitters related to the endocannabinoid system -- the same ones affected by cannabis -- decreased after drinking four to eight cups of coffee in a day. That's the opposite of what occurs after someone uses cannabis. The study also gives possible insight in the cause of munchies. Coffee may also increase the elimination of steroids.
Teens who are old for their grade appear to feel more confident about their academic abilities and are more likely to enroll in college than their younger peers, according to new research.
Working with lab-grown human brain cells, researchers report they have uncovered a much sought-after connection between one of the most common genetic mutations in Parkinson's disease and the formation of fatty plaques in the brain thought to contribute to the destruction of motor neurons that characterize the disease.
A new study finds that e-cigarette use could do more harm than good by substantially increasing the number of adolescents and young adults who eventually become cigarette smokers and marginally decreasing the number of adult cigarette smokers who quit.
Better hand grip strength may be associated with cardiac functions and structures that help reduce the risk of cardiovascular incidents, according to a new study.

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