tbuckley/cabot-search huggingface dataset:
Single nucleotide polymorphisms in miRNA binding sites of nucleotide excision repair-related genes to predict clinical benefit of oxaliplatin in FOLFOXIRI plus bevacizumab in TRIBE trial.
Authors: Mitsukuni Suenaga, Marta Schirripa, Shu Cao, Wu Zhang, Dongyun Yang, Chiara Cremolini, Sabina Murgioni, Sara Lonardi, Yan Ning, Satoshi Okazaki, Martin D Berger, Yuji Miyamoto, Roel Gopez, Afsaneh Barzi, Fotios Loupakis, Alfredo Falcone, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2018)

663 Background: Nucleotide excision repair (NER) is known as part of the DNA damage response (DDR) against platinum-induced DNA damage. Polymorphisms in miRNA binding sites of replication protein A ( RPA2) and General Transcription Factor IIH Subunit 1 ( GTF2H1) genes in NER pathway have shown to correlate with colorectal cancer risk. We tested whether the NER-related single nucleotide polymorphisms (SNPs) predict oxaliplatin efficacy in FOLFOXIRI regimen in patients (pts) with metastatic colorectal cancer (mCRC). Methods: Genomic DNA was extracted from 457 blood samples of mCRC pts enrolled in the TRIBE trial: 230 pts received first-line (1L) FOLFOXIRI plus bevacizumab (discovery cohort: median age, 60 yrs; median follow-up, 46.6 mos); and 227 pts received 1L FOLFIRI plus bevacizumab (control cohort: median age, 60 yrs; median follow-up, 49.0 mos). SNPs were analyzed by PCR-based direct sequencing. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression. Results: In KRAS wild-type population among the discovery cohort, the C/C variant in RPA2 rs7356 was associated with shorter PFS and OS than any T allele (9.1 vs 13.3 mos, HR 2.32, 95%CI: 1.07-5.03, P= 0.020; 20.8 vs 37.1 mos, HR 1.94, 95%CI: 0.94-3.99, P= 0.059). Any C allele in GTF2H1 rs4596 was associated with shorter PFS than the G/G variant (10.8 vs 13.3 mos, HR1.64, 95%CI: 0.95-2.81, P= 0.045). In multivariable analysis, RPA2 rs7356 remained significant for PFS and OS (HR 2.97, 95%CI: 1.27-6.94, P= 0.012; HR 2.58, 95%CI: 1.19-5.58, P= 0.016). In all population of the discovery cohort, pts with any GTF2H1 rs4596 C allele had remarkably shorter PFS and OS than those with the G/G variant (11.3 vs 13.2 mos, HR 1.32, P= 0.087; 28.6 vs 34.3 mos, HR 1.36, P= 0.076). The findings remained in multivariable analysis. These findings were not confirmed in the control cohort. Conclusions: We suggest that miRNA binding sites of NER-related genes regulate DDR for oxaliplatin-related DNA damage. Germline RPA2 and GTF2H1 polymorphisms may predict oxaliplatin efficacy in mCRC pts.
Cytokine-dependent activation of MAIT cells by the TLR8 agonist GS-9688 but not the TLR7 agonist GS-9620
Authors: S. Daffis, M. Morar, D. Pattabiraman, C. Voitenleitner, S. Fletcher, H. Javanbakht
Journal: Journal of Hepatology (2018)
Intravenous Immune Globulin to Prevent Heparin-Induced Thrombocytopenia
Authors: Theodore E Warkentin, Troy H Climans, Pierre-Aurèle Morin
Journal: New England Journal of Medicine (2018)

Intravenous Immune Globulin to Prevent HIT Anti–platelet factor 4–heparin antibodies present a major risk of heparin-induced thrombocytopenia (HIT). The use of intravenous immune globulin neutralized large amounts of these antibodies in a patient so that heparin could be used safely during emergency surgery.
Changes in the characteristics of hospital admissions due to complications of cirrhosis in the era of direct-acting antivirals against HCV
Authors: M. Fraile, L. Franco, A. Gomez, M. Torner, A. Castano-Garcia, P.F. Díez, V.J. Beltrán, N.R. Ferreiro, M. Varela, M. Luisa, G. Dieguez, V. Cadahía-Rodrigo, C. Álvarez-Navascués, M. Rodríguez
Journal: Journal of Hepatology (2018)
Variation in coagulation and fibrinolysis genes evaluated for their contribution to cerebrovascular complications in adults with bacterial meningitis in the Netherlands
Authors: A.T. Kloek, H.N. Khan, M. Valls Seron, A. Jongejan, A.H. Zwinderman, F. Baas, A. van der Ende, D. van de Beek, B. Ferwerda, M.C. Brouwer
Journal: Journal of Infection (2018)
TCTAP A-120 Clinical Factors and Long Term Prognosis of New-onset Atrial Fibrillation in Patients Hospitalized with ST-elevation Myocardial Infarction
Authors: Kyu-Yong Ko, Sang-Don Park, Ji-Hun Jang, Yong-Soo Baek, Sung Woo Kwon, Sung-Hee Shin, Seong-Ill Woo, Dae-Hyeok Kim, Jun Kwan
Journal: Journal of the American College of Cardiology (2018)
Abstract 20024: Rivaroxaban Attenuates Pressure Overload-Induced Vulnerability to Atrial Fibrillation via the Suppresion of Protease Activated Receptor-2 Activation by Factor Xa
Authors: Miho Haraguchi, Hidekazu Kondo, Naohiko Takahashi
Journal: Circulation (2016)

Introduction:  Coagulation factor Xa not only promotes thrombus formation, but also exacerbates inflammation via activation of protease activated receptor-2 (PAR-2).   Hypothesis:  We tested the hypotheses whether oral administration of RVX would attenuate transverse aortic constriction (TAC)-induced atrial inflammatory fibrosis and vulnerability to AF in mice.   Methods:  Six-week old male CL57/B6 mice were divided into Sham-operation (CNT) group and TAC-surgery group. Furthermore these two groups were then subdivided into vehicle (VEH) group and RVX treatment group (30mg/kg/day). By using rat cultured cells, PAR-2 expression in response to TAC-related stimulation were assessed.   Results:  We observed followings. 1) Tail vein bleeding time and prothrombin time by two hours after RVX administration were significantly prolonged in RVX treatment groups. 2) TAC-induced left atrial thrombi were not observed in TAC-RVX group (62.5% vs. 0%, p   Conclusions:  These observations demonstrated that rivaroxaban may have the cardio-protective effect against pressure overload-induced atrial remodeling.
Untreated HCV in HIV/HCV co-infection: Data from the TRIO network
Authors: D. Jayaweera, K. Althoff, J. Eron, G. Huhn, S. Milligan, A. Mills, G. Moyle, S. Santiago, P. Sax, G. Voskuhl, D. Wyles, R. Elion
Journal: Journal of Hepatology (2018)
Hepatic microRNA and phosphoproteomic analysis provide insights about hepatic collagen deposition and stage of fibrosis in non-alcoholic steatohepatitis
Authors: Z. Younossi, A. Karrar, K. Tokarz, M. Pierobon, A. Ulyanov, M. Stepanova, Z. Younoszai, T. Jeffers, S. Felix, D. Tan, J. Kianoush, A. Hodge, M. Ahmad, R. Iyer, V. Chandho, E. Petricoin, J. Deeken, Z. Goodman
Journal: Journal of Hepatology (2018)
Hodgkin lymphoma-like post-transplant lymphoproliferative disorder (HL-PTLD): Characteristics, survival, and prognostication in a large U.S. cohort.
Authors: Aaron Seth Rosenberg, Andreas Kirschmer Klein, Robin Ruthazer, Andrew M. Evens
Journal: Journal of Clinical Oncology (2014)

8572 Background: Post-transplant lymphoproliferative disorder is a well described complication of solid organ transplant (SOT), however relatively little is known about HL-PTLD. Methods: We examined a large cohort of HL-PTLD (1999-2011) in the Scientific Registry of Transplant Recipients (SRTR), focusing on detailed characteristics, overall survival (OS), and prognostic factors. Cox-proportional hazards models were utilized to estimate hazard ratios (HR) and 95% confidence intervals (CI); and we compared characteristics and OS with HL pts from SEER 18. Results: We identified 204 HL-PTLD pts. Median age at diagnosis was 52 years (0-80); 74% were male, 82% Caucasian and the most common SOT was renal (52%). Median time from SOT to HL-PTLD was 6.9 years (<0.1-20 years), while tumor was EBV+ in 73%. Older pts were more likely to have EBV- disease (OR 1.42/decade, (95% CI 1.14-1.81), P<0.01), however early vs late HL-PTLD was not associated with EBV status. Compared with SEER HL, HL-PTLD pts were older (median 52 vs 38 years, P=0.006), more often male (74% vs 55%, P<0.001) and with more extranodal (43% vs 3%, P<0.001). Median OS for HL-PTLD was 6.3 years with 3- and 5-year OS rates of 65% and 55%, respectively. These rates were significantly inferior compared with SEER HL pts (83% and 79%, respectively, P<0.001). For HL-PTLD pts, age (HR 1.29/decade (95% CI 1.15-1.44) P<0.001), EBV- (2.03 (95% CI 1.03-4.01) P=0.04), increased creatinine (Cr) (HR 1.87 (95% CI 1.43-2.44) P<0.01), and performance status <80 (HR 2.10 (95% CI 1.06-4.17) P=0.03) were associated with increased risk of death. When controlling for age, only Cr remained significant. Finally, on multivariable analysis controlling for diagnosis date, age, sex and extranodal status, HL-PTLD pts had twice the risk of death (HR 2.05 (95% CI 1.65-2.55) P<0.001) vs SEER HL pts. Conclusions: These data represent the largest report of HL-PTLD to date. HL-PTLD pts are commonly older, male, and have EBV+ disease, the latter despite typically having “late” PTLD. The dominant factors predicting OS were age and Cr. In addition, OS for HL-PTLD was modest and significantly inferior to a SEER HL population. Continued study of HL-PTLD is needed.
TCTAP A-113 Impact of Mitral Annular Calcification on Immediate Hemodynamic and Echocardiographic Results of Percutaneous Transvenous Mitral Commissurotomy in Patients of Symptomatic Mitral Stenosis
Authors: Toufiqur Rahman, Afzalur Rahman, Abdullah Al Shafi Majumder, AKM Monwarul Islam
Journal: Journal of the American College of Cardiology (2018)
Abstract 16479: Mir20a Regulates Tissue Factor Expression in Human Peripheral Blood Mononuclear Cells Exposed to High Glucose and Lipopolysaccharide
Authors: Cristina Balia, Mirella Giordano, Valentina Scalise, Silvana Cianchetti, Tommaso Neri, Gabriella Fontanini, Fulvio Basolo, Alessandro Celi, Roberto Pedrinelli
Journal: Circulation (2016)

Introduction: Inflammation and coagulation are deeply interconnected phenomena, a mechanism amplified by Angiotensin(AT)II that upregulates Tissue Factor (TF), the major regulator of haemostasis an...
Neurologist’s 2500 patients are recalled over concerns about diagnoses
Authors: Clare Dyer
Journal: BMJ (2018)

All 2500 patients of a consultant neurologist in Northern Ireland have been recalled amid concerns about his diagnoses and treatment plans in the biggest patient recall ever in the province.

Michael Watt, who specialises in stroke, Parkinson’s disease, and multiple sclerosis, is a senior consultant at Royal Victoria Hospital in Belfast. He also practised privately.

“Other doctors raised concerns with the trust regarding the care and treatment provided by Dr Michael Watt to a small number of patients,” said Mark Mitchelson, medical chair of division at Belfast Health and Social Care Trust.

The …
Abstract B19: Tumor-suppressive activities associated to MIR10A-5p expression in developmental sarcomas
Authors: David Herrero-Martin, Santiago Rello-Varona, Silvia Garcia-Monclus, Juan Huertas-Martinez, Olga Almacellas-Rabaiget, Lee J. Helman, Oscar M. Tirado
Journal: Clinical Cancer Research (2018)

Abstract Ewing sarcoma (ES) and alveolar rhabdomyosarcoma (ARMS) are pediatric sarcomas characterized by tumor-specific translocations. Besides acting as a direct modulator of transcription, fusion proteins appear to exert its oncogenic functions by epigenetic modifications on the transcriptome. Therefore, the identification of specific DNA methylation markers would be helpful for understanding their pathogenetic mechanism as well as for developing new therapeutic strategies. By using the Illumina Infinium HumanMethylation450 we have analyzed the methylome of ES and ARMS tumors and cell lines. ES and ARMS samples showed, among other epigenetic alterations, differential hypermethylation in the promoter of MIR10A-5p, thus suggesting an inhibition of its expression. Expression of MIR10A-5p is effectively low in ES and ARMS cell lines and patient samples and the treatment with the epigenetic modifier 5-aza restores its expression. MIR10A-5p stable overexpression in two ES (A673 and TC252) and two ARMS (Rh4 and RMS13) cell lines reduces proliferation, diminishes clonogenic growth, and decreases cellular migration. Cell death induced by MIR10A-5p reintroduction is only achieved in the p53wt ES cell line TC252. Proteomic profile of A673 MIR10A-5p cells is altered as assessed by iTRAQ. Protein kinase CRKL is one of the proteins downregulated due to MIR10A-5p reintroduction. Indeed, CRKL expression is also reduced in the other three MIR10A-5p stable overexpression models. Doxycycline-induced silencing of CRKL in ARMS cell line Rh30 provokes cell growth reduction in vitro and in vivo, G0/G1 arrest, and a decrease in the clonogenic capacity (Yeung CL et al., 2013). Interestingly, the migratory ability of Rh30 and A673 CRKL-silenced cells is also impaired. Thus, our results uncover MIR10A-5p as a putative tumor suppressor in ES and ARMS, suggesting a link between MIR10A-5p and CRKL. Further characterization of the oncogenic role of CRKL and the molecular mechanisms associated to MIR10A-5p tumor-suppressor activities in ES and ARMS is ongoing. Citation Format: David Herrero-Martin, Santiago Rello-Varona, Silvia Garcia-Monclus, Juan Huertas-Martinez, Olga Almacellas-Rabaiget, Lee J. Helman, Oscar M. Tirado. Tumor-suppressive activities associated to MIR10A-5p expression in developmental sarcomas [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr B19.
Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma
Authors: Janet E. Murphy, Jennifer Y. Wo, David P. Ryan, Wenqing Jiang, Beow Y. Yeap, Lorraine C. Drapek, Lawrence S. Blaszkowsky, Eunice L. Kwak, Jill N. Allen, Jeffrey W. Clark, Jason E. Faris, Andrew X. Zhu, Lipika Goyal, Keith D. Lillemoe, Thomas F. DeLaney, Carlos Fernández-del Castillo, Cristina R. Ferrone, Theodore S. Hong
Journal: JAMA Oncology (2018)

Patients with borderline-resectable pancreatic ductal adenocarcinoma have historically poor outcomes with surgery followed by adjuvant chemotherapy. Evaluation of a total neoadjuvant approach with highly active therapy is warranted.To evaluate the margin-negative (R0) resection rate in borderline-resectable pancreatic ductal adenocarcinoma after neoadjuvant FOLFIRINOX (fluorouracil, irinotecan, and oxaliplatin) therapy and individualized chemoradiotherapy.A single-arm, phase 2 clinical trial was conducted at a large academic hospital with expertise in pancreatic surgery from August 3, 2012, through August 31, 2016, among 48 patients with newly diagnosed, previously untreated, localized pancreatic cancer determined to be borderline resectable by multidisciplinary review, who had Eastern Cooperative Oncology Group performance status 0 or 1 and adequate hematologic, renal, and hepatic function. Median follow-up for the analysis was 18.0 months among the 30 patients still alive at study completion.Patients received FOLFIRINOX for 8 cycles. Upon restaging, patients with resolution of vascular involvement received short-course chemoradiotherapy (5 Gy × 5 with protons) with capecitabine. Patients with persistent vascular involvement received long-course chemoradiotherapy with fluorouracil or capecitabine.The primary outcome was R0 resection rate; secondary outcomes were median progression-free survival (PFS) and median overall survival (OS).Of the 48 eligible patients, 27 were men and 21 were women, with a median age of 62 years (range, 46-74 years). Of the 43 patients who planned to receive 8 preoperative cycles of chemotherapy, 34 (79%) were able to complete all cycles. Twenty-seven patients (56%) had short-course chemoradiotherapy, while 17 patients (35%) had long-course chemoradiotherapy. R0 resection was achieved in 31 of the 48 eligible patients (65%; 95% CI, 49%-78%). Among the 32 patients who underwent resection, the R0 resection rate was 97% (n = 31). Median PFS among all eligible patients was 14.7 months (95% CI, 10.5 to not reached), with 2-year PFS of 43%; median OS was 37.7 months (95% CI, 19.4 to not reached), with 2-year OS of 56%. Among patients who underwent resection, median PFS was 48.6 months (95% CI, 14.4 to not reached) and median OS has not been reached, with a 2-year PFS of 55% and a 2-year OS of 72%.Preoperative FOLFIRINOX followed by individualized chemoradiotherapy in borderline resectable pancreatic cancer results in high rates of R0 resection and prolonged median PFS and median OS, supporting ongoing phase 3 trials.ClinicalTrials.gov Identifier: NCT01591733.
TCTAP A-006 Utility of GRACE and ACUITY-HORIZONS Risk Scores to Guide Dual Antiplatelet Therapy in Patients with Acute Myocardial Infarction Undergoing Drug-eluting Stenting
Authors: Doo Sun Sim, Myung-Ho Jeong, Hyo-Soo Kim, Hyeon-Cheol Gwon, Ki-Bae Seung, Dong Joo Oh, Shung Chull Chae, Chong-Jin Kim, Kwang Soo Cha, Young-Jo Kim, Junghan Yoon, Jei Keon Chae, Seung-Jae Joo, Dong-Ju Choi, Kwon-Bae Kim, In-Whan Seong, Myeong-Chan Cho, Doo Il Kim, Seok Kyu Oh, Taehoon Ahn, Jin Yong Hwang
Journal: Journal of the American College of Cardiology (2018)
Role of Stem Cell–Like Memory T Cells in Systemic Lupus Erythematosus
Authors: Ye Ji Lee, Ji Ah Park, Hyunmi Kwon, Youn Soo Choi, Kyeong Cheon Jung, Seong Hoe Park, Eun Bong Lee
Journal: Arthritis & Rheumatology (2018)

Stem cell-like memory T (Tscm) cells are long-lived memory T cells that have multipotent capacity to differentiate into different subsets. However, the role of Tscm cells in autoimmune diseases remains unclear. Here, we performed phenotypic studies to identify Tscm cells in patients experiencing systemic lupus erythematosus (SLE).CD4+ and CD8+ Tscm cells were identified in SLE patients and healthy controls (HCs). In in vitro culture systems, CD4+ Tscm cells were induced to differentiate into subsets of T cells, including follicular helper T (Tfh) cells, and cytokine production patterns were assessed after stimulation. After confirming induction of transcription factors for Tfh cells, the capacity of CD4+ Tscm-derived Tfh cells to help B cells was analyzed by measuring antibody secretion.The percentages of CD4+ and CD8+ Tscm cells among the naive CD4+/CD8+ or total CD4+ T cell populations were significantly higher in SLE patients than in HCs. Stimulated Tscm cells from SLE patients could replenish themselves and differentiate into other T lymphocyte subsets, including Tfh cells upon stimulation with T cell receptor. Production of T cell factor 1, which is an inducer of Tfh, was also increased. The differentiated Tfh cells increased antibody production by autologous B cells.Taken together, these findings suggest that Tscm cells play a role in the pathogenesis of SLE by maintaining Tfh cells.
David Oliver: Tube feeding and deteriorating patients—guidelines can take us only so far
Authors: David Oliver
Journal: BMJ (2018)

Like most geriatricians, I look after many patients with progressive vascular or Lewy body dementia, severe disabling stroke, near end stage Parkinson’s disease, and other progressive neurological conditions.

The natural history of patients with such conditions is that many run into problems with swallowing and lose their strength of cough. They’re at risk of aspiration pneumonia. They find it hard to meet daily caloric requirements and risk poor nutrition. They may find it hard to take key medicines, which can further worsen swallowing, alertness, or overall medical fitness.

Family carers often do sterling work helping their loved ones to eat and drink on the wards, which even the most conscientious nurses find hard to match. In some families or cultures the idea of withdrawing intravenous fluids or artificial nutritional support, and focusing on palliative care, can require several sensitive and lengthy conversations, over days or weeks, for clinicians and …
Trends in healthcare utilization in the United States and Europe associated with patient with acute hepatic porphyria with recurrent attacks in EXPLORE: A prospective, multinational natural history study of patients with acute hepatic porphyria
Authors: L. Gouya, M. Balwani, D.M. Bissell, D. Rees, U. Stölzel, J. Phillips, R.K. Kauppinen, J.L. Langendonk, R. Desnick, J.C. Deybach, H. Bonkovsky, C. Parket, H. Naik, M. Badminton, P. Stein, E. Minder, J. Windyga, P. Martasek, M.D. Cappellini, P. Ventura, E. Sardh, P. Harper, S. Sandberg, A. Aarsand, F. Alegre, A. Ivanova, N. Talbi, A. Chan, K. Mccarthy, W. Querbes, C. Penz, S. Agarwal, A. Simon, K. Anderson
Journal: Journal of Hepatology (2018)
Molecularly Engineered Biolubricants for Articular Cartilage
Authors: Giulia Morgese, Edmondo M. Benetti, Marcy Zenobi‐Wong
Journal: Advanced Healthcare Materials (2018)

Abstract Lubrication within articular joints plays a crucial role in daily life, providing an extremely low coefficient of friction and preventing wear at the surface of the articular cartilage. Natural biomacromolecules responsible for lubrication are part of the synovial fluid and their degradation is associated with the onset of degenerative diseases, such as osteoarthritis (OA). The current absence of effective treatments for OA has captured the attention of chemists and material scientists over the last two decades, triggering the development of partially or fully synthetic biolubricants aimed to reduce friction within the joints and restore cartilage functions. Although there is still a long way to go before synthetic replacements of natural biolubricants can be applied clinically, this review highlights those formulations that meet the fundamental requirements for being efficient lubricants for articular cartilage.
Fusion Imaging During the Interventional Closure of Patent Foramen Ovale and Atrial Septal Defects
Authors: Shazia Afzal, Verena Veulemans, Laura Kleinebrecht, Dominique Stuewe, Jan Balzer, Amin Polzin, Niels Nijhof, Malte Kelm, Tobias Zeus, Katharina Hellhammer
Journal: JACC. Cardiovascular imaging (2018)
Step-wise strategy for Chinese Budd-Chiari syndrome patients: Long-term outcome of a large scaleprospective observational cohort
Authors: Q. Wang, J. Fan, B. Luo, C. He, W. Guo, X. Yuan, J. Tie, K. Li, W. Bai, T. Yu, J. Niu, Z. Wang, Y. Zhu, N. Han, J. Yuan, X. Li, L. Liu, H. Chen, Y. Lv, H. Liu, E. Wang, D. Xia, L. Zuo, J. Xia, Z. Yin, D. Fan, G. Han
Journal: Journal of Hepatology (2018)
Safety of tildrakizumab for moderate-to-severe plaque psoriasis: pooled analysis of three randomized controlled trials
Authors: A. Blauvelt, K. Reich, K.A. Papp, A.B. Kimball, M. Gooderham, S.K. Tyring, R. Sinclair, D. Thaçi, Q. Li, N. Cichanowitz, S. Green, C. La Rosa
Journal: British Journal of Dermatology (2018)

Short-term interleukin-23p19 inhibition by tildrakizumab improves plaque psoriasis and appears to be well tolerated.Safety and tolerability were assessed for up to 64 weeks of tildrakizumab therapy using pooled data from three randomized controlled trials for moderate-to-severe psoriasis.Data pools for the placebo-controlled (up to 16 weeks) and full trial periods (up to 64 weeks) were analysed (n = 2081).In the placebo-controlled period, frequencies of treatment-emergent adverse events (TEAEs; range 47·9-54·0%), serious TEAEs (range 1·4-2·3%), discontinuations due to AEs (range 0·6-1·9%), major adverse cardiovascular events (MACEs; range 0·0-0·1%) and severe infections (range 0·0-0·3%) were comparable between tildrakizumab 100 mg, tildrakizumab 200 mg, placebo and etanercept. In the full trial period, exposure-adjusted rates (patients per 100 patient-years) for TEAEs, serious TEAEs and discontinuations due to AEs with tildrakizumab 100 mg and 200 mg were lower than or comparable with the placebo rates, and lower than with etanercept. Exposure-adjusted rates of MACEs (range 0·0-0·5) and severe infections (range 0·9-2·0) were comparable among groups. No TEAEs of inflammatory bowel disease or suicide were reported. Candida skin infections were infrequent at frequencies of 0·1%, 0·3%, 0·0% and 0·0% for the tildrakizumab 100 mg, tildrakizumab 200 mg, placebo and etanercept groups, respectively, in the placebo-controlled period, and exposure-adjusted rates of 0·2, 0·7, 0·0 and 0·0, respectively, in the full trial period. Oral candidiasis was also infrequent.Up to 64 weeks of tildrakizumab was well tolerated, with low rates of serious TEAEs, discontinuations due to AEs, and AEs of clinical interest.