tbuckley/cabot-search huggingface dataset:
Abstract 13018: Apoa1 Binding Protein Inhibits Retinal Angiogenesis by Up-regulating Notch Signaling
Authors: Renfang Mao, Yury I Miller, Longhou Fang
Journal: Circulation (2016)

ApoA-1 binding protein (AIBP), a highly evolutionary conserved protein, plays a vital role in zebrafish angiogenesis, but its role of angiogenesis in higher vertebrate has not been studied. We thus propose that the role of AIBP in angiogenesis is also conserved from zebrafish to mice to humans. Since mouse models display tremendous power in the study of human cardiovascular disease as the murine and human vasculatures are highly similar. Therefore, we generated Apoa1bp -/- mice, which are viable and fertile. We then compared retinal vasculature development in Apoa1bp -/- mice and wild-type mice by whole mount immunostaining. Our data show that AIBP deficiency in mice results in significantly enhanced angiogenesis. Mechanically, We found the expressions of the Notch downstream targets Hes1 , Hey1 and Hey2 were upregulated in Apoa1bp -/- retinas compared to controls. And the protein level of Notch intracellular domain (NICD) was decreased in Apoa1bp -/- retinas. These results suggest that the activity of the Notch signaling is decreased in retinas from Apoa1bp -/- mice. Furthermore, we found AIBP affects on γ-secretase activity by enhance the colocaliztion of Notch1 and γ-secretase. Moreover, we studied whether increased HDL levels can rescue retinal angiogenesis in Apoa1bp -/- mice. We crossed ApoA1 transgenic mice with Apoa1bp -/- mice. As expected, increased HDL levels rescued dysregulated angiogenesis in Apoa1bp -/- mice, indicating that AIBP regulates angiogenesis through its effect on lipid rafts. Our study demonstrated that AIBP positively regulates the Notch signaling pathway by effect on lipid rafts, which in turn inhibits retinal angiogenesis. We are the first to connect AIBP, a cholesterol metabolism regulator, to Notch signaling.
Non-invasive genotyping and monitoring of tumor evolution in locally advanced rectal cancer (LARC) patients using circulating tumor DNA (ctDNA)
Authors: S. Toomey, A. Sartori, D. Irwin, S. Hummel, A. Carr, C.L. Lee, P. Armstrong, A. Farrelly, S. El-Masry, D. McNamara, P.G. Morris, L. Grogan, O.S. Breathnach, L. O’Sullivan, S. Bradshaw, A.N.A.M. Rashed, R. Smyth, J. Workman, B. O’Neill, B. Hennessy
Journal: Annals of Oncology (2018)
P2.16-14 Results of Stereotactic Radiation Therapy (SABR) in Early Stage Lung Cancer: Turkish Radiation Oncology Group (TROG) Study
Authors: B. Atalar, E. Kaytan Sağlam, Z. Akgün, U. Abacioglu, A. Arifoglu, B. Sahin, E. Ozyar, G. Yaprak, N. Ozseker Isik, H. Caglar Ozkok, S. Karaman, S. Igdem, U. Selek, F. Öner Dincbas, M. Sengoz, S. Başkaya Yucel, A. Nur Demiral, S. Akyurek
Journal: Journal of Thoracic Oncology (2018)
MA27.07 Lung Adenocarcinoma Harboring BRAF G469V Mutation is Uniquely Sensitive to EGFR Tyrosine Kinase Inhibitors
Authors: H. Notsuda, N. Pham, M. Li, N. Liu, V. Raghavan, Z. Fang, C. Marshall, N. Moghal, M. Ikura, M. Tsao
Journal: Journal of Thoracic Oncology (2018)
JCSE01.15 Molecular Characteristics of ALK Primary Point Mutations Non-Small-Cell Lung Cancer in Chinese Patients
Authors: J. Lai, W. Wang, C. Xu, Q. Zhang, W. Zhuang, Y. Huang, Y. Zhu, Y. Chen, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2018)
The clinical features and genomic landscape of elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in patients with colorectal cancer
Authors: M.-H. Chen, S.-C. Chang, P.-C. Lin, S.-H. Yang, C.-C. Lin, Y.-T. Lan, H.-H. Lin, C.-H. Lin, W.-Y. Liang, W.-S. Chen, J.-K. Jiang, J.-K. Lin
Journal: Annals of Oncology (2018)
Ryanodine Receptor Glycation Favors Mitochondrial Damage in the Senescent Heart
Authors: Marisol Ruiz-Meana, Marta Minguet, Diana Bou-Teen, Elisabet Miro-Casas, Celia Castans, Jose Castellano, Elena Bonzon-Kulichenko, Alberto Igual, Rafael Rodriguez-Lecoq, Jesús Vázquez, David Garcia-Dorado
Journal: Circulation (2019)

Background: Senescent cardiomyocytes exhibit a mismatch between energy demand and supply that facilitates their transition toward failing cells. Altered calcium transfer from sarcoplasmic reticulum (SR) to mitochondria has been causally linked to the pathophysiology of aging and heart failure. Methods: Because advanced glycation-end products accumulate throughout life, we investigated whether intracellular glycation occurs in aged cardiomyocytes and its impact on SR and mitochondria. Results: Quantitative proteomics, Western blot and immunofluorescence demonstrated a significant increase in advanced glycation-end product–modified proteins in the myocardium of old mice (≥20months) compared with young ones (4-6months). Glyoxalase-1 activity (responsible for detoxification of dicarbonyl intermediates) and its cofactor glutathione were decreased in aged hearts. Immunolabeling and proximity ligation assay identified the ryanodine receptor (RyR2) in the SR as prominent target of glycation in aged mice, and the sites of glycation were characterized by quantitative mass spectrometry. RyR2 glycation was associated with more pronounced calcium leak, determined by confocal microscopy in cardiomyocytes and SR vesicles. Interfibrillar mitochondria—directly exposed to SR calcium release—from aged mice had increased calcium content compared with those from young ones. Higher levels of advanced glycation-end products and reduced glyoxalase-1 activity and glutathione were also present in atrial appendages from surgical patients ≥75 years as compared with the younger ones. Elderly patients also exhibited RyR2 hyperglycation and increased mitochondrial calcium content that was associated with reduced myocardial aerobic capacity (mitochondrial O 2 consumption/g) attributable to less respiring mitochondria. In contracting HL-1 cardiomyocytes, pharmacological glyoxalase-1 inhibition recapitulated RyR2 glycation and defective SR-mitochondria calcium exchange of aging. Conclusions: Mitochondria from aging hearts develop calcium overload secondary to SR calcium leak. Glycative damage of RyR2, favored by deficient dicarbonyl detoxification capacity, contributes to calcium leak and mitochondrial damage in the senescent myocardium.
Abstract 11181: Presentation With Cardiac Arrest in Patients With Acute Coronary Syndromes: Insights From the Second Gulf Registry of Acute Coronary Events
Authors: Amar M Salam, Khalid F AlHabib, Wael Almahmeed, Alawi Alsheikh-Ali, Kadhim Sulaiman, Haitham Amin, Jawad Al-Lawati, Ahmed Al-Motarreb, Nidal Asaad, Rajvir Singh, Jassim Al Suwaidi
Journal: Circulation (2014)

OBJECTIVES: There is very scarce contemporary data about the prognostic impact of presentation with cardiac arrest in patients with acute coronary syndromes (ACS), particularly from the developing countries. Accordingly, we sought to assess the incidence, clinical features, immediate and long term mortality of patients with cardiac arrest at presentation using data from a large multicenter Middle-Eastern ACS registry. METHODS: For a period of 9 months in 2008 to 2009, consecutive patients with ACS were enrolled from 65 hospitals in 6 Middle East countries. Patients presenting with cardiac arrest in this cohort were selected and in-hospital outcomes, one-month and one-year mortality were examined. RESULTS: Among 7,930 ACS patients enrolled, there were 89 patients hospitalized alive after resuscitation from cardiac arrest with a rate of 1.1%. Compared with patients without cardiac arrest, patients presenting with cardiac arrest had a significantly higher rate of prior myocardial infarction (32.6% vs. 19.6%)...
P3.01-89 Upfront Surgery Versus Neoadjuvant Treatment Followed by Surgery in Pathologic N2 Non-Small Cell Lung Cancer
Authors: S.K. Kim, H.S. Park, K.D. Cho, D.G. Cho, Y.H. Park, J. Yoo, S.H. Kim, J.M. Ko, E.J. Park, G.R. Heo, C.H. Kim, B.Y. Shim
Journal: Journal of Thoracic Oncology (2018)
NORDIC9: A randomized phase II trial comparing first-line palliative full-dose monotherapy (S-1) with reduced dose-combination therapy (SOx) in older and frail patients with metastatic colorectal cancer (mCRC)
Authors: S.B. Winther, H. Skuladottir, E. Hofsli, C.-H. Shah, M.K. Yilmaz, P.J. Österlund, Å Berglund, B. Glimelius, C. Qvortrup, H. Sorbye, P. Pfeiffer
Journal: Annals of Oncology (2018)
P2.15-21 Post Resection Lung Cancer Surveillance: Comparisons of Practice Between STS, ESTS and JACS Members
Authors: C. Pompili, M. Edwards, S. Hasegawa, I. Yoshino, M. Chida, N. Novoa, A. Brunelli, P. Bhandari, K. Naunheim, L. Backhus
Journal: Journal of Thoracic Oncology (2018)
P2.04-25 Randomized Clinical Trial Comparing Immunotherapy Plus SABR (I-SABR) Versus SABR Alone for Early Stage NSCLC
Authors: J. Chang, L. Feng, S.H. Lin, J.W. Welsh, M.B. Antonoff, D. Gomez, J. Heymach
Journal: Journal of Thoracic Oncology (2018)
P2.13-18 A Multicenter Prospective Biomarker Study to Explore Mechanisms of Afatinib Resistance Based on Digita PCR and Next-Generation Sequencing
Authors: E. Iwama, K. Sakai, K. Azuma, D. Harada, K. Nosaki, K. Hotta, M. Nishio, T. Kurata, T. Fukuhara, H. Akamatsu, K. Goto, T. Shimose, J. Kishimoto, Y. Nakanishi, K. Nishio, I. Okamoto
Journal: Journal of Thoracic Oncology (2018)
Phase I study: Safety and tolerability of varlitinib (VAR) in combination with oxaliplatin and capecitabine (COX) or oxaliplatin and 5-FU (FOL) in advanced solid tumours
Authors: A. Seet, S.P. Choo, D.W.M. Tai, Y.C.J. Lam, W.T. Teng, C. Lim, T.K.H. Lim, I.B. Tan, E. Petricoin, M. Ng
Journal: Annals of Oncology (2018)
P2.06-41 Differentiating Sarcomatoid Mesothelioma from Pleomorphic Carcinoma and Chest Wall Sarcoma Using GATA-3/MUC4/BAP1 IHC
Authors: Y.Z. Zhang, T. Adefila-Ideozu, A. Bowman, A. Januszewski, S. Popat, S. Jordan, J. Robertus, A. Rice, M. Moffatt, W. Cookson, A. Nicholson
Journal: Journal of Thoracic Oncology (2018)
Temozolomide Induces Senescence and Repression of DNA Repair Pathways in Glioblastoma Cells via Activation of ATR–CHK1, p21, and NF-κB
Authors: Dorthe Aasland, Laura Götzinger, Laura Hauck, Nancy Berte, Jessica Meyer, Melanie Effenberger, Simon Schneider, Emelie E. Reuber, Wynand P. Roos, Maja T. Tomicic, Bernd Kaina, Markus Christmann
Journal: Cancer Research (2018)

Abstract The DNA-methylating drug temozolomide, which induces cell death through apoptosis, is used for the treatment of malignant glioma. Here, we investigate the mechanisms underlying the ability of temozolomide to induce senescence in glioblastoma cells. Temozolomide-induced senescence was triggered by the specific DNA lesion O6-methylguanine (O6MeG) and characterized by arrest of cells in the G2–M phase. Inhibitor experiments revealed that temozolomide-induced senescence was initiated by damage recognition through the MRN complex, activation of the ATR/CHK1 axis of the DNA damage response pathway, and mediated by degradation of CDC25c. Temozolomide-induced senescence required functional p53 and was dependent on sustained p21 induction. p53-deficient cells, not expressing p21, failed to induce senescence, but were still able to induce a G2–M arrest. p14 and p16, targets of p53, were silenced in our cell system and did not seem to play a role in temozolomide-induced senescence. In addition to p21, the NF-κB pathway was required for senescence, which was accompanied by induction of the senescence-associated secretory phenotype. Upon temozolomide exposure, we found a strong repression of the mismatch repair proteins MSH2, MSH6, and EXO1 as well as the homologous recombination protein RAD51, which was downregulated by disruption of the E2F1/DP1 complex. Repression of these repair factors was not observed in G2–M arrested p53-deficient cells and, therefore, it seems to represent a specific trait of temozolomide-induced senescence. Significance: These findings reveal a mechanism by which the anticancer drug temozolomide induces senescence and downregulation of DNA repair pathways in glioma cells.
JCSE01.16 Positive Correlation Between Whole Genomic Copy Number Variant Scoring and the Grading System in Lung Non-Mucinous Invasive Adenocarcinoma
Authors: Z. Wang, S. Li, L. Zhang, L. He, D. Cui, C. Liu, Y. Gong, B. Liu, X. Li, W. Wu, D. Cram, D. Liu
Journal: Journal of Thoracic Oncology (2018)
P1.16-43 Analyses of Long-Term Outcomes and Prognostic Factors in Surgically Resected ALK-Rearranged Lung Adenocarcinoma
Authors: Y. Matsuura, J. Ichinose, M. Nakao, M. Mun, K. Nakagawa, H. Ninomiya, Y. Ishikawa, M. Nishio, S. Okumura
Journal: Journal of Thoracic Oncology (2018)
GRIPT: a novel case-control analysis method for Mendelian disease gene discovery
Authors: Jun Wang, Li Zhao, Xia Wang, Yong Chen, Mingchu Xu, Zachry T. Soens, Zhongqi Ge, Peter Ronghan Wang, Fei Wang, Rui Chen
Journal: Genome biology (2018)

Despite rapid progress of next-generation sequencing (NGS) technologies, the disease-causing genes underpinning about half of all Mendelian diseases remain elusive. One main challenge is the high genetic heterogeneity of Mendelian diseases in which similar phenotypes are caused by different genes and each gene only accounts for a small proportion of the patients. To overcome this gap, we developed a novel method, the Gene Ranking, Identification and Prediction Tool (GRIPT), for performing case-control analysis of NGS data. Analyses of simulated and real datasets show that GRIPT is well-powered for disease gene discovery, especially for diseases with high locus heterogeneity.
Author Correction: Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps
Authors: Valentina Iotchkova, Jie Huang, John A Morris, Deepti Jain, Caterina Barbieri, Klaudia Walter, Josine L Min, Lu Chen, William Astle, Massimilian Cocca, Patrick Deelen, Heather Elding, Aliki-Eleni Farmaki, Christopher S Franklin, Mattias Franberg, Tom R Gaunt, Albert Hofman, Tao Jiang, Marcus E Kleber, Genevieve Lachance, Jian’an Luan, Giovanni Malerba, Angela Matchan, Daniel Mead, Yasin Memari, Ioanna Ntalla, Kalliope Panoutsopoulou, Raha Pazoki, John R B Perry, Fernando Rivadeneira, Maria Sabater-Lleal, Bengt Sennblad, So-Youn Shin, Lorraine Southam, Michela Traglia, Freerk van Dijk, Elisabeth M van Leeuwen, Gianluigi Zaza, Weihua Zhang, Najaf Amin, Adam Butterworth, John C Chambers, George Dedoussis, Abbas Dehghan, Oscar H Franco, Lude Franke, Mattia Frontini, Giovanni Gambaro, Paolo Gasparini, Anders Hamsten, Aaron Isaacs, Jaspal S Kooner, Charles Kooperberg, Claudia Langenberg, Winfried Marz, Robert A Scott, Morris A Swertz, Daniela Toniolo, Andre G Uitterlinden, Cornelia M van Duijn, Hugh Watkins, Eleftheria Zeggini, Mathew T Maurano, Nicholas J Timpson, Alexander P Reiner, Paul L Auer, Nicole Soranzo
Journal: Nature Genetics (2018)
Randomized trial of lisinopril or carvedilol for the prevention of cardiotoxicity in patients with early stage HER2-positive breast cancer receiving trastuzumab
Authors: P.N. Munster, J. Krischer, R. Tamura, L. Bello-Matricaria, A. Fink, W. McCaskill-Stevens, M. Guglin
Journal: Annals of Oncology (2018)
Prognostic factors in patients with advanced biliary tract cancer (BTC) who showed durable disease control with first-line gemcitabine plus cisplatin (GemCis)
Authors: J. Hyung, C. Yoo, K.-P. Kim, B.J. Kim, J.H. Jeong, H.-M. Chang, B.-Y. Ryoo
Journal: Annals of Oncology (2018)
Phase II study of NAB-paclitaxel in sensitive and refractory relapsed SCLC (NABSTER TRIAL)
Authors: F. Gelsomino, M. Tiseo, F. Barbieri, F. Riccardi, L. Cavanna, A. Frassoldati, A. Delmonte, L. Longo, C. Dazzi, S. Cinieri, I. Colantonio, M. Tognetto, D. Baldari, L. Tofani, A. Ardizzoni
Journal: Annals of Oncology (2018)
P1.16-47 Adjuvant Targeted Therapy Following Standard Adjuvant Therapy for Resected NSCLC: An Initial Report from ALCHEMIST (Alliance A151216)
Authors: G. Oxnard, S. Mandrekar, S. Hillman, A. Tan, R. Govindan, D. Wigle, S. Malik, C. Watt, D. Gerber, J. Chaft, S. Dahlberg, K. Kelly, M. Faggen, P. Stella, K. Tazi, D. Gandara, S. Ramalingam, T. Stinchcombe
Journal: Journal of Thoracic Oncology (2018)
Cushing Syndrome Is Associated With Subclinical LV Dysfunction and Increased Epicardial Adipose Tissue
Authors: Flavia Maurice, Bénédicte Gaborit, Clara Vincentelli, Ines Abdesselam, Monique Bernard, Thomas Graillon, Frank Kober, Thierry Brue, Frédéric Castinetti, Anne Dutour
Journal: Journal of the American College of Cardiology (2018)
Folfox and intra-arterial DEBIRI as front-line treatment in patients with non resectable colorectal cancer liver metastases (FFCD 1201 phase II trial)
Authors: S. Pernot, P. Artru, D. Tougeron, C. Montérymard, D. Smith, C. De La Fouchardière, J.-L. Raoul, L. Dahan, R. Guimbaud, P. Michel, J.-L. Jouve, O. Pellerin, J. Taieb
Journal: Annals of Oncology (2018)
Ribociclib (RIB) + tamoxifen (TAM) or a non-steroidal aromatase inhibitor (NSAI) in premenopausal patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC): MONALEESA-7 patient-reported outcomes (PROs)
Authors: N. Harbeck, R. Villanueva, F. Franke, G. Babu, P. Wheatley-Price, Y.-H. Im, K. Altundag, B. Lanoue, J. Alam, D. Chandiwana, M. Colleoni
Journal: Annals of Oncology (2018)
P3.01-37 Phase II Study of Amrubicin Plus Erlotinib in Previously Treated, Advanced Non-Small Cell Lung Cancer Patients with Wild-Type EGFR: TORG 1320
Authors: S. Hosokawa, S. Otani, J. Sasaki, T. Fukui, Y. Nakahara, A. Bessho, N. Fukamatsu, Y. Nakamura, T. Kasai, T. Sugiyama, T. Tokitho, N. Seki, A. Hamada, N. Masuda, H. Okamoto
Journal: Journal of Thoracic Oncology (2018)
Monitoring the effect of PI3K inhibition on HER2 therapy resistant breast cancer using serial analysis of PIK3CA mutant tumour DNA in plasma
Authors: N. Keegan, S. Toomey, A. Farrelly, A. Carr, G. Calzaferri, J. Walshe, G. Gullo, J.P. Crown, K. Egan, A. Hernando, A. Teiserskiene, L. Grogan, O.S. Breathnach, P.G. Morris, B. Hennessy
Journal: Annals of Oncology (2018)
OA06.06 MISSILE-NSCLC: A Phase II Trial Measuring the Integration of Stereotactic Radiotherapy Plus Surgery in Early-Stage Non-Small Cell Lung Cancer
Authors: D. Palma, A. Louie, R. Malthaner, D. Fortin, G. Rodrigues, B. Yaremko, J. Laba, K. Kwan, S. Gaede, T. Lee, A. Ward, A. Warner, R. Inculet
Journal: Journal of Thoracic Oncology (2018)
NCI 9922: Phase II study of ibrutinib in treatment-refractory distant metastatic cutaneous melanoma (DMCM)
Authors: S.J. Moschos, Z. Eroglu, N.I. Khushalani, K.L. Kendra, G. Ansstas, G.K. In, P. Wang, G. Liu, F.A. Collichio, C.C. Arrowood, J.E. Reed, N. Garrett-Mead, N.E. Thomas, D.W. Ollila, S.P. Ivy, A. Ivanova, E.C. Dees, J.L. Abbruzzese
Journal: Annals of Oncology (2018)
Impact of tissue processing and interferents on the reproducibility and robustness of a multi-plex gene expression assay measuring tumor inflammation
Authors: B. Wallden, S. Church, I. Pekker, S. Zimmerman, S. Popa, A. Sullivan, C. Ngouenet, E. Harris, N. Dowidar, A. Bergdahl, C. Schaper, P. Danaher, S. Ferree
Journal: Annals of Oncology (2018)
P3.08-08 Outcomes of Pulmonary Metastasectomy in Breast Cancer: Prognosis Based on the Metastatic Lung Tumor Study Group of Japan
Authors: M. Endoh, S. Shiono, N. Matsutani, S. Okumura, N. Ikeda, I. Yoshino, J. Nakajima, M. Kawamura
Journal: Journal of Thoracic Oncology (2018)
Prolonged urinary and bowel symptom control in men with non-metastatic castration-resistant prostate cancer (nmCRPC) treated with enzalutamide: Results from the PROSPER study
Authors: B. Tombal, M. Hussain, D. Penson, G. Attard, C.N. Sternberg, D. Phung, R. Morlock, K. Modelska, K. Ramaswamy, C. Ivanescu, F. Saad
Journal: Annals of Oncology (2018)
P2.06-23 Association of Two BRM Promoter Polymorphisms and Tobacco Exposure with Malignant Pleural Mesothelioma (MPM) Risk and Survival
Authors: M.J. Lee, N. Kuehne, K. Hueniken, H. Sorotsky, M. Liang, D. Patel, D. Cheng, Z. Chen, L. Eng, M.C. Brown, J. Cho, N. Leighl, M. De Perrot, D. Reisman, W. Xu, P. Bradbury, G. Liu
Journal: Journal of Thoracic Oncology (2018)
Selective induction of PD-L1 expression in plasma-derived exosomes by gemcitabine-nab-paclitaxel vs. FOLFIRINOX in pancreas cancer
Authors: E. Rofi, M. Del Re, C. Vivaldi, S. Crucitta, E. Arrigoni, G. Pasquini, S. Catanese, I. Pecora, G. Musettini, E. Vasile, A. Falcone, R. Danesi
Journal: Annals of Oncology (2018)
EUMelaReg: A European platform for outcome research on real world treatment data of patients with advanced melanoma
Authors: M. Weichenthal, A.C.J. van Akkooi, P. Mohr, E. Ellebaek, I.-M. Svane, S. Ugurel-Becker, U. Leiter, L. Hoejberg, J.B.A.G. Haanen, H. Schmidt, T.H. Oellegaard, M.W.J.M. Wouters, D. Schadendorf, L. Bastholt
Journal: Annals of Oncology (2018)
Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination
Authors: Germaine Hanquet, Pavla Krizova, Palle Valentiner-Branth, Shamez N Ladhani, J Pekka Nuorti, Agnes Lepoutre, Jolita Mereckiene, Mirjam Knol, Brita A Winje, Pilar Ciruela, Maria Ordobas, Marcela Guevara, Eisin McDonald, Eva Morfeldt, Jana Kozakova, Hans-Christian Slotved, Norman K Fry, Hanna Rinta-Kokko, Emmanuelle Varon, Mary Corcoran, Arie van der Ende, Didrik F Vestrheim, Carmen Munoz-Almagro, Pello Latasa, Jesus Castilla, Andrew Smith, Birgitta Henriques-Normark, Robert Whittaker, Lucia Pastore Celentano, Camelia Savulescu
Journal: Thorax (2018)

Background Pneumococcal conjugate vaccines (PCVs) have the potential to prevent pneumococcal disease through direct and indirect protection. This multicentre European study estimated the indirect effects of 5-year childhood PCV10 and/or PCV13 programmes on invasive pneumococcal disease (IPD) in older adults across 13 sites in 10 European countries, to support decision-making on pneumococcal vaccination policies. Methods For each site we calculated IPD incidence rate ratios (IRR) in people aged ≥65 years by serotype for each PCV10/13 year (2011–2015) compared with 2009 (pre-PCV10/13). We calculated pooled IRR and 95% CI using random-effects meta-analysis and PCV10/13 effect as (1 − IRR)*100. Results After five PCV10/13 years, the incidence of IPD caused by all types, PCV7 and additional PCV13 serotypes declined 9% (95% CI −4% to 19%), 77% (95% CI 67% to 84%) and 38% (95% CI 19% to 53%), respectively, while the incidence of non-PCV13 serotypes increased 63% (95% CI 39% to 91%). The incidence of serotypes included in PCV13 and not in PCV10 decreased 37% (95% CI 22% to 50%) in six PCV13 sites and increased by 50% (95% CI −8% to 146%) in the four sites using PCV10 (alone or with PCV13). In 2015, PCV13 serotypes represented 20–29% and 32–53% of IPD cases in PCV13 and PCV10 sites, respectively. Conclusion Overall IPD incidence in older adults decreased moderately after five childhood PCV10/13 years in 13 European sites. Large declines in PCV10/13 serotype IPD, due to the indirect effect of childhood vaccination, were countered by increases in non-PCV13 IPD, but these declines varied according to the childhood vaccine used. Decision-making on pneumococcal vaccination for older adults must consider the indirect effects of childhood PCV programmes. Sustained monitoring of IPD epidemiology is imperative.