tbuckley/cabot-search huggingface dataset:
Checkpoint inhibition immunotherapy for advanced local and systemic conjunctival melanoma: a clinical case series
Authors: Paul T. Finger, Anna C. Pavlick
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Herein, we describe the use of systemic immunotherapy for both locally advanced and metastatic conjunctival melanoma. Current treatments for advanced conjunctival melanoma typically result in poor local control leading to disfiguring orbital exenteration surgery. Locoregional spread of conjunctival malignant melanoma typically requires pre-auricular and cervical lymph node dissection with post-operative adjuvant radiation therapy. In addition, classic systemic chemotherapy has been unsuccessful in the treatment of metastatic disease. <h3>Methods</h3> This is a retrospectively analyzed clinical case series of 5 patients with biopsy proven conjunctival melanoma who were treated with checkpoint inhibition therapy. Of these, 3 patients were treated for residual ocular disease present after failing multiple local therapies and refusing orbital exenteration surgery and two (with local ocular control) for metastatic conjunctival melanoma. Both those with locally advanced disease and patients with metastatic disease received an anti-PD1 agent in combination with another immunotherapeutic agent. All 5 were given multiple cycles of systemic anti-PD1 therapy, 1 was initially treated with single agent ipilimumab (3 mg/kg) prior to approval of anti-PD1 agents and two received interferon eye drops. As part of each ophthalmic examination, photographs of all conjunctival and eyelid surfaces were obtained. Systemic evaluations involved initial staging scans as well as periodic re-imaging. <h3>Results</h3> All cases have shown responses. Of the 2 complete responses, 1 was a patient with systemic disease. No patients developed ocular toxicity or loss of vision. However, systemic adverse effects included adrenal insufficiency, Grade-III colitis, Grade-II dermatitis, Grade-II hepatotoxicity and Grade-II pneumonitis. <h3>Conclusions</h3> This report suggests that systemic immunotherapy with or without topical interferon is effective in treatment of malignant melanoma of the conjunctiva. Therefore, it can be considered for patients with advanced local conjunctival melanoma, those who refuse orbital exenteration surgery and those with systemic metastasis.
Association of recurrent or progressive p of form types II and III pleuropulmonary blastoma (PPB) with poor outcome: A report from the international PPB registry.
Authors: Kris Ann Pinekenstein Schultz, Gretchen M Williams, Douglas Stewart, Philip S Rosenberg, Leslie Ann Doros, Louis P Dehner, D Ashley Hill, Yoav H. Messinger
Journal: Journal of Clinical Oncology (2015)

10014 Background: Pleuropulmonary blastoma (PPB) is a rare malignancy of the lung presenting in young children. PPB is the sentinel disease of the PPB-DICER1familial syndrome. The International PPB Registry (IPBBR) has pathologically confirmed 425 cases of PPB. Three pathologic subtypes correlate with outcome: Type I/Ir, purely cystic; Type II, combined cystic solid; Type III, purely solid. Five-year survival rates for Types I/Ir, II and III PPB are 91%, 71% and 53%, respectively. The outcome of Type II and III PPB after a relapse (recurrence or progression) is unknown. Methods: Yearly follow-up is requested for all patients by the IPPBR. All PPB was confirmed by central pathology review. Reports of relapse and second malignancies were obtained by the IPPBR from the local institution. In most cases, the pathology of relapse or second malignancy was available for additional central review. Results: A total of 107 PPB patients relapsed, of them 35 (33%) were alive at a median of 15 months (range 0-61) and 72 (67%) had died at a median of 10 months (range 0-60). Twenty-nine (27%) relapsed with isolated CNS metastasis, 51 (48%) with isolated chest relapse, and 27 (25%) with other relapse; of them 66%, 53% and 96% respectively have died. Of the survivors, 34/35 (97%) had isolated disease either in the chest or CNS. In addition to the patients with recurrence, 6 patients had secondary malignancies believed to be related to prior therapy and 5 had a metachronous DICER1-related tumor; of these 83% and 100% respectively, were alive. Conclusions: In this cohort of centrally-reviewed relapsed PPB only one-third were alive at last follow-up. Patients with isolated CNS or chest maybe sometimes survive, but patients with bone metastasis rarely survive. Novel treatment regimens for relapsed PPB are urgently needed. Alive Dead Total Relapse -Isolated CNS 10 (34%) 19 (66%) 29 -Isolated chest 24 (47%) 27 (53%) 51 -Other (combined chest + CNS or systemic) 1 (4%) 26 (96%) 27 Total Relapse 35 (33%) 72 (67%) 107 Secondary malignancy 5 (83%) 1 (17%) 6 DICER1-related metachronous malignancies* 5 (100%) 0 (0%) 5 *Thyroid carcinoma, Sertoli-Leydig cell tumor, cervical embryonal rhabdomyosarcoma.
SAT-181-Efficacy and safety of glecaprevir/pibrentasvir in patients with severe renal impairment in Japan: A prospective, multicenter study (KTK 49 Liver Study Group)
Authors: Masanori Atsukawa, Makoto Nakamuta, Takashi Kumada, Hidenori Toyoda, Koichi Takaguchi, Tsunamasa Watanabe, Hiroki Ikeda, Akito Nozaki, Atsushi Hiraoka, Kojiro Michitaka, Hiroshi Abe, Keizo Kato, Noritomo Shimada, Toru Asano, Haruki Uojima, Chikara Ogawa, Shinya Fukunishi, Akira Asai, Takuya Genda, Shigeru Mikami, Tadashi Ikegami, Akihito Tsubota, Yoshio Aizawa, Naoki Hotta, Shinichi Fujioka, Hironao Okubo, Norio Itokawa, Taeang Arai, Chisa Kondo, Etsuko Iio, Yasuhito Tanaka, Katsuhiko Iwakiri
Journal: Journal of Hepatology (2019)
Update on valganciclovir as add-on therapy for glioblastoma: Effect in de novo and recurrent disease.
Authors: Giuseppe Stragliotto, Afsar Rahbar, Cecilia Soederberg-Naucler
Journal: Journal of Clinical Oncology (2015)

e22199 Background: Since the overall survival of patients with glioblastoma is still very limited with current combined therapy of surgery and radiochemotherapy, we have studied the potential effect of adding valganciclovir early after diagnosis, or at relapse. Our earlier retrospective results on 50 patients have shown significant prolonged survival . The median survival increased to 24 months and the 2 years survival was 62%. Methods: This is an updated retrospective amalysis of glioblastoma patients treated at a single institution. Valganciclovir tablets 450mg 2x2 were given during the initial 3 weeks as induction therapy, followed by maintenance 1 x 2 continuously, until disease progression and/or late palliative situation. Ten patients receiving valganciclovir during shorter period are not included : early progression (3), hematologic toxicity grade III (1), non compliance (4) patient stopped intake early (2). Results: Seventy patients with newly diagnosed glioblastoma received valganciclovir for 6 months (which was the duration of the first phase II exploratory study: VIGAS) or longer. The follow-up is at least 1 year. Of the patients that have died, the median survival is 22 months (9-72 months, n = 44), the patients with shorter survival had partial resection. Twenty-six patients are alive, and the median survival is 18 months (4-88 months). In twenty-five patients with recurrence, valganciclovir was added to salvage therapy ( 3 underwent reoperation before starting valganciclovir), relapse treatment was heterogeneous (second line chemotherapy-CCNU in general, a few received re-irradiation up to 34 Gy and 3 radiosurgery). The median survival after recurrence was 9 months (1-24 months, n = 25). Conclusions: The addition of valganciclovir prolonged survival in newly diagnosed glioblastoma patients. There was no additional toxicity when valganciclovir was combined to chemotherapy. The effect in recurrent patients is more limited, because patients were treated late. Earlier therapy at recurrence in patients with good function may have better effect. Larger randomized trials of anti CMV therapy are planned.
Effects of hyperonic saline solution and continuous positive airway pressure on respiratory mucus contact angle and mucus transportability by cough in cystic fibrosis patients
Authors: E. S. Aquino, D. M Goto, A. S. Santos, C. C. Coelho, M. B. Fuccio, Paulo Hilário Nascimento Saldiva, Geraldo Lorenzi Filho, N. K. Nakagawa
Journal: American Journal of Respiratory and Critical Care Medicine (2008)
FRI-096-Technetium-99m-GSA within the first 3d after admission as an early predictor of outcome in severe acute liver injury
Authors: Yuji Suzuki, Keisuke Kakisaka, Takuro Sato, Hiroaki Abe, Tokio Sasaki, Takehiro Akiyama, Yasuhiro Takikawa
Journal: Journal of Hepatology (2019)
Abstract P371: Twenty-Five-Year (1986-2011) Trends in the Incidence and In-Hospital Case-fatality Rates of Stroke Complicating Acute Myocardial Infarction
Authors: Essa Hariri, Mayra Tisminetzky, Robert Goldberg
Journal: Circulation (2018)

Introduction: Stroke after acute myocardial infarction (AMI) is an important complication resulting in increased morbidity and mortality. However, limited long-term trends data are available about the incidence and death rates associated with this serious complication. Objective: The aim of this study is to examine the 25-year trends in the incidence rates and outcomes of initial episodes of stroke complicating AMI. Hypothesis: We hypothesize that the incidence and outcomes of stroke complicating AMI would decrease over time with recent advances in the management of both diseases. Methods: The study population consisted of 11,433 adults hospitalized with validated AMI at all 11 medical centers in central Massachusetts on a biennial basis between 1986-2011. Results: Of 11,436 patients (mean age = 69 years; 42% female) without a history of stroke hospitalized with confirmed AMI, 159 patients (1.4%) experienced an acute stroke during their index hospitalization. The proportion of patients with AMI who developed a stroke increased through the 1990s but declined slightly thereafter (Figure 1). Patients who experienced an acute stroke were significantly older, more likely to be female, had a previous AMI, had a significant burden of comorbidities, and were more likely to have developed atrial fibrillation, heart failure, and have died (32.1% versus 10.8%; p&lt;0.001) during their index hospitalization compared with patients who did not develop a stroke. Patients developing a stroke in the most recent years (2003-2011) were 5 times more likely to have died during hospitalization compared to those who did not develop a stroke (OR, 5.05; 95% CI, 2.34-10.90). Conclusions: In conclusion, the incidence rates of acute stroke complicating AMI remained relatively stable during the years under study but with an increased likelihood of dying during hospitalization. Better characterization of factors associated with the risk of stroke remains important for the more optimal care of this vulnerable population.
THU-237-Increasing prevalence of indications to choose bone/renal-friendly antiviral drug: A territory-wide study of 135,414 patients from 2000 to 2017
Authors: Grace Lai-Hung Wong, Becky Wing-Yan Yuen, Yee-Kit Tse, Hester Wing-Sum Luk, Terry CF Yip, Henry Chan, Vincent Wai-Sun Wong
Journal: Journal of Hepatology (2019)
Learning About Dupilumab-Associated Conjunctivitis—Reply
Authors: Alison D. Treister, Cheryl Kraff-Cooper, Peter A. Lio
Journal: JAMA Dermatology (2019)

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Improving the Patient Protection and Affordable Care Act's Insurance Coverage Provisions: A Position Paper From the American College of Physicians
Authors: Ryan A. Crowley, Sue S. Bornstein
Journal: Annals of Internal Medicine (2019)

The coverage reforms of the Patient Protection and Affordable Care Act have fundamentally changed the U.S. health care system. The law's health insurance regulations, which include protections for persons with preexisting conditions, have made health insurance more accessible. The premium tax credit and cost-sharing subsidies have made nongroup coverage more affordable. The essential health benefit package and coverage for preventive services without cost sharing have made insurance more comprehensive. Perhaps most important, the Medicaid expansion extended coverage to millions of low-income adults. Despite these gains, more needs to be done to bring the United States closer to achieving universal coverage. In this position paper, the American College of Physicians recommends action to enhance and expand eligibility for health insurance financial subsidies; stabilize health insurance marketplaces; provide sustained funding for outreach, education, and enrollment assistance activities; test and implement a mechanism to encourage enrollment; expand Medicaid in all states; and establish a public insurance option to increase competition.
Impact on KRAS-subtypes and TP53 mutations on the prognostic value of KRAS/KEAP1 comutations in non-small cell lung cancer (NSCLC)
Authors: M. Scheffler, R. Frank, M.A. Ihle, D.S. Abdulla, S. Koleczko, L. Nogova, A. Holzem, T. Chanra, R. Riedel, S. Michels, R.N. Fischer, A. Kron, S. Merkelbach-Bruse, R. Buettner, J. Wolf
Journal: Annals of Oncology (2019)

Background: Recent studies suggest a devastating impact of KEAP1 mutations on survival in systemically treated advanced NSCLC for both KRAS-comutated and KRAS-wildtype patients. KRAS G12C mutations differ in their co-mutational properties from other KRAS mutations, and TP53 mutations affect the outcome in a subset of NSCLC like ALK-positive NSCLC. We set out this analysis to determine the impact of both KRAS G12C and co-occurring TP53 mutations on the prognostic value of KRAS/KEAP1 comutations. Methods: We pooled the data from three different analyses between 2013 and 2018 and looked for patients with stage IV NSCLC for whom survival data was available and who received systemic therapy. The patients had to be diagnosed by a comprehensive next-generation sequencing panel, comprising at least KRAS, KEAP1and TP53 mutations. Median overall survival (mOS) was assessed using Kaplan Meier statistics. Results: We identified 35 patients with KRAS/KEAP1 comutation and available survival data. G12C was detected in 22 patients (62.9%). A co-occurring TP53 mutation could be found in 15 patients (42.9%), and 11 patients (31.4%) presented with both aberrations beside a KEAP1 mutation. 15 patients (42.9%) had neither comutation. The mOS for the whole cohort was 9.8 months (95% CI, 6.3-13.3 months). Neither the presence of a G12C mutation (mOS 9.8 months [5.7-13.4], log rank p = 0.724) nor the presence of a co-occurring TP53 mutation (mOS 9.0 months [5.8-12.2], log rank p = 0.407) had a significant influence on the outcome. For G12C/TP53 beside KEAP1 mutations, there was hardly any difference to the comparison cohort (mOS 9.8 months [5.4-14.2], log rank p = 0.998). Patients without G12C and TP53 had an mOS of 10.4 months (3.6-17.2 months, log rank p = 0.467). Conclusions: The comutation status of TP53 mutations and/or the presence of the KRAS G12C subtype have no impact on the prognostic value of KRAS/KEAP1-mutated stage IV NSCLC. Further investigations are ongoing to reveal the influence of the mode of systemic therapy in larger cohorts to confirm these findings. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
FRI-150-Association of the immunodominant HLA-B35:01 restricted CD8+ T cell epitope with clustered viral evolution in HBV polymerase
Authors: Elahe Salimi Alizei, Michael Muthamia Kiraithe, Philipp Ehrenmann, Maike Hofmann, Robert Thimme, Christoph Neumann-Haefelin
Journal: Journal of Hepatology (2019)
SAT-399-The profile on intracellular gangliosides correlates with the malignant phenotype of cholangiocarcinoma cells and modulates cells adhesion
Authors: Chiara Raggi, Antonella Mannini, Margherita Correnti, Elisabetta Rovida, Jesper Andersen, Cedric Coulouarn, Fabio Marra
Journal: Journal of Hepatology (2019)
Abstract 16081: Precisely Controlled Arterial CO2 as an Alternative to Pharmacological Stress Agents for Potentiating Myocardial Blood Flow: A Preclinical Study in Canines With and Without Coronary Stenosis
Authors: Hsin-jung Yang, Damini Dey, Jane Sykes, Michael Klein, John Butler, Michael Kovacs, Olivia Sobczyk, Behzad Sharif, Xiaoming Bi, Avinash Kali, Ivan Cokic, Richard Tang, Roya Yumul, Antonio Conte, Sotirios Tsaftaris, Mourad Tighiouart, Debiao Li, Piotr Slomka, Daniel Berman, Frank Prato, Joseph Fisher, Rohan Dharmakumar
Journal: Circulation (2017)

Introduction: Increases in partial pressure of arterial CO2 (PaCO2) has been known to modulate myocardial blood flow (MBF). However, challenges in blood gas control and limited availability of vali...
THU-174-Efficacy of L-Carnitine on the ribavirin induced hemolytic anemia for patients with HCV infection
Authors: Shinya Sato, Kei Moriya, Tadashi Namisaki, Kosuke Kaji, Hiroaki Takaya, Takemi Akahane, Hideto Kawaratani, Yasuhiko Sawada, Yukihisa Fujinaga, Masanori Furukawa, Hitoshi YOSHIJI
Journal: Journal of Hepatology (2019)
FRI-325-rs641738 C &gt; T variant near MBOAT7-TMC4 increases risk of fibrosis, NASH, and HCC: A meta-analysis
Authors: Kevin Teo, Amedine Duret, Dana de Gracian Hahn, Harriet Hunter, Yu Ri Im, Madison Fairey, Mrudula Utukuri, Jiawen Dong, Hong Lim, Jake Mann
Journal: Journal of Hepatology (2019)
FRI-301-The differential expression of the CIDE family is associated with NAFLD progression from steatosis to steatohepatitis
Authors: Sans Arnaud, Bonnafous Stéphanie, Rousseau Déborah, Patouraux Stéphanie, Canivet Clémence, Leclere Pierre, Tran-Van-Nhieu Jeanne, Luci Carmelo, Bailly-Maitre Béatrice, Minehira Kaori, Anty Rodolphe, Tran Albert, Iannelli Antonio, Philippe Gual
Journal: Journal of Hepatology (2019)
Abstract 09: Excess Weight, Cardiovascular Events, and Healthy Longevity: The Lifetime Risk Pooling Project
Authors: Sadiya S Khan, Hongyan Ning, John T Wilkins, Norrina B Allen, Mercedes Carnethon, Jarett D Berry, Ranya N Sweis, Donald M Lloyd-Jones
Journal: Circulation (2017)

Background: Compared with normal BMI, overweight status (body-mass index [BMI] 25.0-29.9 kg/m 2 ) appears to be associated with greater longevity, but it is unclear to what extent this comes at the expense of greater burden of cardiovascular disease (CVD) and years lived with CVD. Methods: We pooled individual-level data from 10 prospective cohorts and included adults free from CVD, stratified by index age (20-39, 40-59, and 60-79 years). We used: (1) modified Kaplan-Meier analysis to estimate lifetime risks for CVD events and non-cardiovascular death; (2) Irwin’s restricted mean to estimate years lived free from and with CVD; and (3) adjusted competing Cox models to estimate joint cumulative risks for CVD or non-cardiovascular death. Results: The mean (SD) baseline BMI in middle-age (ages 40-59 years) was 27.4 (4.1) kg/m 2 for men and 27.1 (6.0) kg/m 2 for women. Through 72,490 person-years of follow-up, 13,457 CVD events (coronary heart disease, stroke, and heart failure; including 6,309 CVD deaths) and 11,782 non-CVD deaths occurred in middle-aged participants. Compared with normal BMI, lifetime risks for CVD were higher in overweight and obese adults. Average years lived free from CVD were longest for normal BMI individuals, whereas years lived with CVD were longer for overweight and obese (FIGURE) . Compared with middle-aged men and women, respectively, with normal BMI, competing hazards ratios (95% CI) for incident CVD were 1.21 (1.14-1.28) and 1.32 (1.24-1.40) for BMI 25.0-29.9; 1.67 (1.55-1.79) and 1.85 (1.72-1.99) for BMI 30-39.9; and 3.14 (2.48-3.97) and 2.53 (2.20-2.91) for BMI 40.0 and greater. Similar patterns were observed in younger and older adults. Conclusions: Compared with normal BMI, both overweight and obesity are associated with similar or shorter total longevity and more years of life lived with CVD. These data suggest that the “obesity/overweight paradox” present after the diagnosis of CVD occurs because of earlier onset of CVD.
Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial
Authors: Karim Fizazi, NamPhuong Tran, Luis Fein, Nobuaki Matsubara, Alfredo Rodriguez-Antolin, Boris Y Alekseev, Mustafa Özgüroğlu, Dingwei Ye, Susan Feyerabend, Andrew Protheroe, Giri Sulur, Yesenia Luna, Susan Li, Suneel Mundle, Kim N Chi
Journal: The Lancet Oncology (2019)