tbuckley/cabot-search huggingface dataset:
Multiple nivolumab-induced CNS demyelination with spontaneous resolution in an asymptomatic metastatic melanoma patient
Authors: Vincent Pillonel, Vincent Dunet, Andreas F. Hottinger, Gregoire Berthod, Luis Schiappacasse, Solange Peters, Olivier Michielin, Veronica Aedo-Lopez
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Immune checkpoint inhibitors (ICPis) have revolutionised the treatment of melanoma by significantly increasing survival rates and disease control. However, ICPis can have specific immune-related adverse events, including rare but severe neurological toxicity. <h3>Case presentation</h3> We report a 44-year-old man diagnosed with stage IIIB melanoma who developed metastatic disease (pulmonary and brain metastases) and was treated with stereotactic radiosurgery and nivolumab immunotherapy. He developed asymptomatic multifocal diffuse white matter lesions consistent with active central nervous system demyelination seen on brain MRI. One month after cessation of the immunotherapy, spontaneous regression of the demyelinating lesions was observed, suggesting a nivolumab-related toxicity. <h3>Conclusion</h3> We report the first case of a melanoma patient with an asymptomatic and spontaneously reversible central nervous system demyelination following nivolumab immunotherapy. This case highlights the need for better recognition of such atypical and rare neurological toxicities which could be mistaken for progressive brain metastases. Early recognition and appropriate management are crucial to reduce severity and duration of these toxicities, especially for patients with less favourable evolution.
Efficacy and safety of pegvorhyaluronidase alfa (PEGPH20; PVHA) and pembrolizumab (pembro) combination therapy in patients (Pts) with stage III/IV non-small cell lung cancer (NSCLC)
Authors: J.P. Ward, M. Shum, E. Bertino, V. Lin, V. Kuruvadi, T. Heineman
Journal: Annals of Oncology (2019)
Interaction kinetics with transcriptomic and secretory responses of CD19-CAR natural killer-cell therapy in CD20 resistant non-hodgkin lymphoma
Authors: Dashnamoorthy Ravi, Saheli Sarkar, Sneha Purvey, Frank Passero, Afshin Beheshti, Ying Chen, Maisarah Mokhtar, Kevin David, Tania Konry, Andrew M. Evens
Journal: Leukemia (2019)
Abstract P212: Health-related Quality of Life and Leukocyte Telomere Length Among Adults in the United States: Findings From the National Health and Nutrition Examination Survey, 2001-2002
Authors: Rumana J Khan, Samson Gebreab, Pia Crespo, Amadou Gaye, Ruihua Xu, Sharon Davis
Journal: Circulation (2016)

Background: Health-related quality of life (HRQOL) is defined as perceived physical and mental health over time. Lower HRQOL has previously been shown to be associated with elevated adverse health events and mortality. Leukocyte telomere length (LTL), which is a biomarker of aging at the cellular level, has also been associated with age-related diseases and mortality. However, the association of HRQOL with LTL in the general population is poorly understood. Objective: We examined the relationship between different measures of HRQOL and LTL by ethnicity among a nationally representative sample of US adults using the data of the National Health and Nutrition Examination Survey (NHANES, 2001-2002). Method: HRQOL were assessed through a brief set of survey-based questions that asked participants about their self-rated general health and the number of recent days when the person was physically unwell, mentally unwell, or limited in usual activities. Telomere length was assessed using the quantitative polymerase chain reaction method of telomere length relative to standard reference DNA. Multiple linear regression was used to estimate the relationship, where we sequentially controlled for demographic (age, sex, education, marital status), health risk indicator (cancer, hypertension, diabetes, obesity, heart failure) and health behavior (smoking, physical activity, and alcohol intake) variables. Log transformed value of LTL was used for regression modeling and all the analyses were estimated with adjustment for sample weights for the genetic sub-sample and design effects. Results: The current study included 2090 White, 788 Mexican American, and 669 African American participants with mean age of 46.89 (Standard Error, SE=0.56), 37.57 (SE=0.73) and 41.99 (SE=0.74) years respectively. After controlling for demographic factors, health risk indicators, and health behaviors, recent days of unwell physical health was associated with shorter telomere length for Whites (beta=-0.005, 95% Confidence Interval, 95% CI=-0.01 to -0.001, p value 0.03). Among African Americans, those who perceived their general health condition as “good” had shorter telomere length compared to those who perceived general health status as “excellent” (beta=-0.02, 95% CI=-0.03 to -0.01, p value 0.001). Mental health related quality of life showed no significant association with LTL in any race. For Mexican Americans none of the HRQOL measures had any association with LTL. Conclusion: Lower physical HRQOL and lower general HRQOL were associated with shorter LTL or faster cellular aging for Whites and African Americans in our study. The results endorse the value of assessing HRQOL,specially in relation to to physical and general health, and the importance of using this measure for evaluating age and disease related consequences.
On-demand pre-exposure prophylaxis with tenofovir disoproxil fumarate plus emtricitabine among men who have sex with men with less frequent sexual intercourse: a post-hoc analysis of the ANRS IPERGAY trial
Authors: Guillemette Antoni, Cécile Tremblay, Constance Delaugerre, Isabelle Charreau, Eric Cua, Daniela Rojas Castro, François Raffi, Julie Chas, Thomas Huleux, Bruno Spire, Catherine Capitant, Laurent Cotte, Laurence Meyer, Jean-Michel Molina, Jean-Pierre Aboulker, Nathalie Bajos, Jean-Guy Baril, Michel Besnier, Johan Binesse, Diane Carette, Grégoire Cattin, Antoine Chéret, Christian Chidiac, Elias Choucair, Jean-François Delfraissy, Baptiste Demoulin, Alpha Diallo, Isabelle Durant-Zaleski, Véronique Doré, Nicolas Etien, Françoise Euphrasie, Julien Fonsart, Valérie Foubert, Séverine Gibowski, Gabriel Girard, Brigitte Guillon, Soizic Le Mestre, France Lert, Nicolas Leturque, Nicolas Lorente, Anaïs Mennecier, Michel Morin, Emmanuelle Netzer, Joanne Otis, Armelle Pasquet, Gilles Peytavin, Gilles Pialoux, Marie Préau, Cécile Rabian, Willy Rozenbaum, Luis Sagaon-Teyssier, Yacine Saïdi, Marine Saouzanet, Marie-Christine Simon, Marie Suzan-Monti, David Thompson, Julie Timsit, Benoît Trottier, Mark Wainberg
Journal: The Lancet HIV (2019)
Real-World Outcomes of Selective Laser Trabeculoplasty in the United Kingdom
Authors: Anthony P. Khawaja, Joanna H. Campbell, Nicholas Kirby, Hitesh S. Chandwani, Ian Keyzor, Mousam Parekh, Andrew I. McNaught, Dubois Vincent, Knox Angela, Anand Nitin, Owora Gbemi, McNaught Andrew, Chang Lydia
Journal: Ophthalmology (2019)

Selective laser trabeculoplasty (SLT) is a common treatment option for managing glaucoma and ocular hypertension. We assessed the real-world effectiveness of SLT and baseline factors associated with treatment success in the United Kingdom.Retrospective observational study of de-identified electronic medical records (Medisoft Glaucoma module [Medisoft Ltd, Leeds, UK]) from 5 UK ophthalmology teaching centers.Adult patients undergoing their first recorded SLT. For bilateral SLT (same day), analyses included 1 randomly selected eye.Patient demographics, procedure details, and clinical outcomes data were extracted. Factors associated with treatment success were assessed using multivariable Cox regression.Change from baseline in intraocular pressure (IOP) and glaucoma medication use at 12 to 18 and 24 to 36 months post-SLT. A Kaplan-Meier survival analysis was also conducted. Failure of SLT was defined as any further glaucoma procedure post-SLT or any of the following at 2 consecutive visits: IOP >21 mmHg, IOP reduction <20% from baseline, or increase in glaucoma medications from baseline.A total of 831 SLT-treated eyes (mean baseline IOP 22.0 mmHg) of 831 patients were analyzed. At 12 to 18 and 24 to 36 months post-SLT, respectively, significant reductions in IOP (-4.2 [95% confidence interval {CI}, -4.7 to -3.7] and -3.4 [95% CI, -4.1 to -2.7] mmHg; both P < 0.0001) and significant increases in the number of glaucoma medications (0.13 [95% CI, 0.04-0.23], P = 0.007, and 0.20 [95% CI, 0.06-0.33], P = 0.005) were observed. Survival analysis demonstrated treatment success in 70%, 45%, and 27% of eyes at 6, 12, and 24 months post-SLT, respectively. Higher baseline IOP was strongly associated with treatment success (hazard ratio [HR], 0.67 for baseline IOP >21 mmHg vs. ≤21 mmHg, 95% CI, 0.57-0.80; P < 0.001). Selective laser trabeculoplasty success was not significantly associated with age (P = 0.78), baseline visual field mean deviation (P = 1.00), or concurrent use of IOP-lowering medication (P = 0.52).Most patients initially responded to SLT, but the majority failed within 1 year. Efficacy of SLT was better in patients with higher baseline IOP but did not differ by glaucoma severity or concurrent use of IOP-lowering medication. These findings may help inform which patients are suitable for SLT therapy.
Phase II Study of Nonmetastatic Desmoplastic Medulloblastoma in Children Younger Than 4 Years of Age: A Report of the Children’s Oncology Group (ACNS1221)
Authors: Lucie Lafay-Cousin, Eric Bouffet, Douglas Strother, Vasilisa Rudneva, Cynthia Hawkins, Charles Eberhart, Craig Horbinski, Linda Heier, Mark Souweidane, Chris Williams-Hughes, Arzu Onar-Thomas, Catherine A. Billups, Maryam Fouladi, Paul Northcott, Giles Robinson, Amar Gajjar
Journal: Journal of Clinical Oncology (2019)

PURPOSE Nodular desmoplastic medulloblastoma (ND) and medulloblastoma with extensive nodularity (MBEN) have been associated with a more favorable outcome in younger children. However, treatment-related neurotoxicity remains a significant concern in this vulnerable group of patients. PATIENTS AND METHODS ACNS1221 was a prospective single-arm trial of conventional chemotherapy for nonmetastatic ND and MBEN based on a modified HIT SKK 2000 regimen excluding intraventricular methotrexate, aiming to achieve similar outcome (2-year progression-free survival [PFS] ≥ 90%) with reduced treatment-related neurotoxicity. Secondary objectives included feasibility of timely central pathology review and evaluation of tumor molecular profile. RESULTS Twenty-five eligible patients (15 males and 10 females; median age, 18.7 months) were enrolled. Eighteen patients had ND and 7 had MBEN histology. Three patients had residual disease at baseline. The study closed early because of a higher than expected relapse rate. Twelve patients experienced relapse—local (n= 6), distant (n = 3), and combined (n = 3)—at a median of 9.8 months from diagnosis (range, 8.9-13.7 months), and 2 patients died of disease. Two-year PFS and overall survival rates were 52% (95% CI, 32.4% to 71.6%) and 92% (95% CI, 80.8% to 100.0%) respectively. Patients older than 12 months of age ( P = .036) and ND histology ( P = .005) were associated with worse PFS. No patients with MBEN histology experienced relapse. All tumor samples clustered within the sonic hedgehog (SHH) group. Methylation analysis delineated 2 subgroups, SHH-I and SHH-II, which were associated with 2-year PFS rates of 30.0% (95% CI, 1.6% to 58.4%) and 66.7% (95% CI, 44.0% to 89.4%), respectively ( P = .099). CONCLUSION The proposed modified regimen of conventional systemic chemotherapy without serial intraventricular methotrexate injection failed to achieve the targeted 2-year PFS of 90%. With this cohort, we prospectively confirmed the existence of two SHH subgroups and observed a trend toward worse outcome for SHH-I patients.
Extracellular Crystal Deposition in Cutaneous Plasmacytosis
Authors: Jung-Woo Ko, Kyung Eun Jung, Chong Won Choi, Young Lee, Young-Joon Seo
Journal: JAMA Dermatology (2019)

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Abstract 12068: Nighttime Home Blood Pressure Had Stronger Correlation With Hypertensive Organ Damage Than Nighttime Ambulatory Blood Pressure: The Japan Morning Surge Home Blood Pressure (J-HOP) Study
Authors: Sirisawat Wanthong, Tomoyuki Kabutoya, Satoshi Hoshide, Kazuomi Kario
Journal: Circulation (2018)

Introduction: Nighttime blood pressure (BP) measured by ambulatory BP monitoring (ABPM) is correlated with hypertensive target organ damage (TOD). Several recent studies had described an associatio...
Effect of asthma exacerbation during pregnancy in women with asthma: a population-based cohort study
Authors: Kawsari Abdullah, Jingqin Zhu, Andrea Gershon, Sharon Dell, Teresa To
Journal: European Respiratory Journal (2019)

The association between asthma exacerbation during pregnancy and adverse maternal and child health outcomes have not been investigated appropriately. Our objective was to determine the short- and long-term intergenerational effect of asthma exacerbation in pregnant women with asthma. A population cohort study was conducted using data from the Ontario asthma surveillance system and population-level health administrative data. Asthma exacerbation in pregnant women with asthma was defined as at least one of the following criteria: at least five physician visits, or one emergency department visit or one hospital admission for asthma during pregnancy. Pregnancy complications, adverse perinatal outcomes and early childhood respiratory disorders were identified using International Classification of Disease codes (9th and 10th revisions). The cohort consisted of 103 424 singleton pregnancies in women with asthma. Asthma exacerbation in pregnant women with asthma was associated with higher odds of pre-eclampsia (OR 1.30, 95% CI 1.12–1.51) and pregnancy-induced hypertension (OR 1.17, 95% CI 1.02–1.33); babies had higher odds of low birthweight (OR 1.14, 95% CI 1.00–1.31), preterm birth (OR 1.14, 95% CI 1.01–1.29) and congenital malformations (OR 1.21, 95% CI 1.05–1.39). Children born to women with asthma exacerbation during pregnancy had elevated risk of asthma (OR 1.23, 95% CI 1.13–1.33) and pneumonia (OR 1.12, 95% CI 1.03–1.22) during the first 5 years of life. Asthma exacerbation during pregnancy in women with asthma showed increased risk of pregnancy complications, adverse perinatal outcomes and early childhood respiratory disorders in their children, indicating that appropriate asthma management may reduce the risk of adverse health outcomes.
Transcriptomic and methylomic features in asthmatic and nonasthmatic twins
Authors: Gopal Krishna R. Dhondalay, Bryan Bunning, Rebecca N. Bauer, Elliot S. Barnathan, Christopher Maniscalco, Frédéric Baribaud, Kari C. Nadeau, Sandra Andorf
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Sequential Ipilimumab After Chemoradiotherapy in Curative-Intent Treatment of Patients With Node-Positive Cervical Cancer
Authors: Jyoti S. Mayadev, Danielle Enserro, Yvonne G. Lin, Diane M. Da Silva, Heather A. Lankes, Carol Aghajanian, Sharad Ghamande, Kathleen N. Moore, Vanessa A. Kennedy, Paula M. Fracasso, Russell J. Schilder
Journal: JAMA Oncology (2019)

Despite standard chemoradiotherapy (CRT), most women with lymph node (LN)-positive cervical cancer experience disease recurrence. Immunotherapy is being investigated in the up-front treatment setting.To assess the safety of sequential immunotherapy after CRT and to investigate human papillomavirus (HPV) genotype and HLA allele status on survival and programmed cell death 1 (PD-1) expression before and after CRT and sequential immunotherapy.This prospective phase 1 trial conducted in 29 Gynecology Oncology Cooperative Group member institutions enrolled participants from December 18, 2012, to August 31, 2016, with a 14.8-month median follow-up and translational end points. Thirty-four women with International Federation of Gynecology and Obstetrics stage IB2 to IVA cervical cancer with positive pelvic LNs, para-aortic LNs, or both were enrolled; 13 did not receive ipilimumab and were excluded from the analysis. Data were analyzed from January 21 to April 4, 2018.Treatment consisted of 6 weekly doses of cisplatin, 40 mg/m2, concurrent with radiotherapy. After completion of chemotherapy, sequential ipilimumab was given every 21 days for 4 doses. Two dosage levels of ipilimumab, 3 mg/kg and 10 mg/kg, were studied to identify the maximum tolerated dose.The primary end point was safety, and the secondary end points were overall survival and progression-free survival. Exploratory end points included HPV genotype, HLA allele status, and PD-1 expression measured in peripheral blood.The median age of the 32 participants included in the intent-to-treat analysis was 50 (range, 26-61) years, and 22 patients (69%) were white. Of the 21 patients who received ipilimumab, all had positive pelvic LN, and 6 (29%) had positive para-aortic LNs. All patients completed CRT, and of the 21 patients who received at least 2 cycles of ipilimumab, 18 (86%) completed 4 cycles of ipilimumab, and 3 (14%) completed 2 cycles. The maximum tolerated dose was 10 mg/kg. Two of the 21 patients (9.5%) who received ipilimumab had self-limiting grade 3 toxic effects (lipase increase; dermatitis). The 12-month overall survival was 90%, and progression-free survival was 81%. Human papillomavirus genotype and HLA subtype were not associated with progression-free survival or overall survival. T cells expressing PD-1 increased after CRT, and levels were sustained with ipilimumab.This study's findings suggest that the use of immunotherapy after CRT for curative-intent treatment of patients with cervical cancer is tolerable and effective. The results indicated that PD-1 was upregulated after CRT and sustained with sequential ipilimumab therapy. These immune findings may help guide future therapies to harness the activated T-cell phenotype in patients with node-positive cervical cancer.
15 Year Follow-up of ABMT for NHL: Surprisingly Favorable Outcome for Younger Adults.
Authors: Hien Duong, Lisa Rybicki, Steven Andresen, Edward Copelan, Robert Dean, Matt Kalaycio, Brad Pohlman, Ronald Sobecks, John Sweetenham, Josephine Chan, Shawnda Sungren, Brian Bolwell
Journal: Blood (2008)
IMbrave150: Efficacy and safety results from a ph III study evaluating atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (Sor) as first treatment (tx) for patients (pts) with unresectable hepatocellular carcinoma (HCC)
Authors: A.-L. Cheng, S. Qin, M. Ikeda, P. Galle, M. Ducreux, A. Zhu, T.-Y. Kim, M. Kudo, V. Breder, P. Merle, A. Kaseb, D. Li, W. Verret, Z. Xu, S. Hernandez, J. Liu, C. Huang, S. Mulla, H.Y. Lim, R. Finn
Journal: Annals of Oncology (2019)
MDM2 inhibitor APG-115 synergizes with PD-1 blockade through enhancing antitumor immunity in the tumor microenvironment
Authors: Douglas D. Fang, Qiuqiong Tang, Yanhui Kong, Qixin Wang, Jiaxing Gu, Xu Fang, Peng Zou, Tao Rong, Jingwen Wang, Dajun Yang, Yifan Zhai
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Programmed death-1 (PD-1) immune checkpoint blockade has achieved clinical successes in cancer therapy. However, the response rate of anti-PD-1 agents remains low. Additionally, a subpopulation of patients developed hyperprogressive disease upon PD-1 blockade therapy. Combination therapy with targeted agents may improve immunotherapy. Recent studies show that p53 activation in the myeloid linage suppresses alternative (M2) macrophage polarization, and attenuates tumor development and invasion, leading to the hypothesis that p53 activation may augment antitumor immunity elicited by anti-PD-1 therapy. <h3>Method</h3> Using APG-115 that is a MDM2 antagonist in clinical development as a pharmacological p53 activator, we investigated the role of p53 in immune modulation and combination therapy with PD-1 blockade. <h3>Results</h3> In vitro treatment of bone marrow-derived macrophages with APG-115 resulted in activation of p53 and p21, and a decrease in immunosuppressive M2 macrophage population through downregulation of c-Myc and c-Maf. Increased proinflammatory M1 macrophage polarization was observed in the spleen from mice treated with APG-115. Additionally, APG-115 has co-stimulatory activity in T cells and increases PD-L1 expression in tumor cells. In vivo, APG-115 plus anti-PD-1 combination therapy resulted in enhanced antitumor activity in <i>Trp53</i><sup><i>wt</i></sup>, <i>Trp53</i><sup><i>mut</i></sup>, and <i>Trp53-</i>deficient (<i>Trp53</i><sup><i>−/−</i></sup>) syngeneic tumor models. Importantly, such enhanced activity was abolished in a syngeneic tumor model established in <i>Trp53</i> knockout mice. Despite differential changes in tumor-infiltrating leukocytes (TILs), including the increases in infiltrated cytotoxic CD8<sup>+</sup> T cells in <i>Trp53</i><sup><i>wt</i></sup> tumors and M1 macrophages in <i>Trp53</i><sup><i>mut</i></sup> tumors, a decrease in the proportion of M2 macrophages consistently occurred in both <i>Trp53</i><sup><i>wt</i></sup> and <i>Trp53</i><sup><i>mut</i></sup> tumors upon combination treatment. <h3>Conclusion</h3> Our results demonstrate that p53 activation mediated by APG-115 promotes antitumor immunity in the tumor microenvironment (TME) regardless of the <i>Trp53</i> status of tumors per se. Instead, such an effect depends on p53 activation in <i>Trp53</i> wild-type immune cells in the TME. Based on the data, a phase 1b clinical trial has been launched for the evaluation of APG-115 in combination with pembrolizumab in solid tumor patients including those with <i>TP53</i><sup><i>mut</i></sup> tumors.
Immune checkpoint inhibitors for patients acquired resistance to tyrosine kinase inhibitors with EGFR mutated non-small cell lung cancer: A multicenter retrospective study
Authors: T. Uenami, M. Mori, T. Shiroyama, I. Nagatomo, S. Ihara, K. Komuta, H. Suzuki, T. Hirashima, M. Kimura, F. Imamura
Journal: Annals of Oncology (2019)