tbuckley/cabot-search huggingface dataset:
Diagnosis and Management of Castleman Disease
Authors: Jeremy S. Abramson
Journal: Journal of the National Comprehensive Cancer Network (2019)

Castleman disease is a heterogeneous nonmalignant lymphoproliferative disorder. Major distinctions include unicentric versus multicentric presentation; hyaline vascular, plasmacytic, or mixed pathology; and HHV8-associated (typically HIV-positive) versus idiopathic disease. At the NCCN 2019 Annual Congress: Hematologic Malignancies, Dr. Jeremy S. Abramson stated that rituximab is preferred as initial therapy for HHV8-positive disease, and chemotherapy can be added for patients with fulminant disease (antiretrovirals should always be used as well for those who are HIV-positive). Siltuximab is the preferred frontline therapy for idiopathic disease.
Single-cell RNA sequencing reveals compartmental remodeling of tumor-infiltrating immune cells induced by anti-CD47 targeting in pancreatic cancer
Authors: Yu Pan, Fengchun Lu, Qinglin Fei, Xingxing Yu, Ping Xiong, Xunbin Yu, Yuan Dang, Zelin Hou, Wenji Lin, Xianchao Lin, Zheyang Zhang, Minggui Pan, Heguang Huang
Journal: Journal of Hematology & Oncology (2019)

Abstract Background Human pancreatic ductal adenocarcinoma (PDAC) responds poorly to immune checkpoint inhibitor (ICPi). While the mechanism is not completely clear, it has been recognized that tumor microenvironment (TME) plays key roles. We investigated if targeting CD47 with a monoclonal antibody could enhance the response of PDAC to ICPi by altering the TME. Methods Using immunohistochemistry, we examined tumor-infiltrating CD68 + pan-macrophages (CD68 + M) and CD163 + M2 macrophages (CD163 + M2) and tumor expression of CD47 and PD-L1 proteins in 106 cases of PDAC. The efficacy of CD47 blockade was examined in xenograft models. CD45 + immune cells from syngeneic tumor models were subjected to single-cell RNA-sequencing (scRNA-seq) by using the 10x Genomics pipeline. Results We found that CD47 expression correlated with the level of CD68 + M but not CD163 + M2. High levels of tumor-infiltrating CD68 + M, CD163 + M2, and CD47 expression were significantly associated with worse survival. CD47 high /CD68 + M high and CD47 high /CD163 + M2 high correlated significantly with shorter survival, whereas CD47 low /CD68 + M low and CD47 low /CD163 + M2 low correlated with longer survival. Intriguingly, CD47 blockade decreased the tumor burden in the Panc02 but not in the MPC-83 syngeneic mouse model. Using scRNA-seq, we showed that anti-CD47 treatment significantly remodeled the intratumoral lymphocyte and macrophage compartments in Panc02 tumor-bearing mice by increasing the pro-inflammatory macrophages that exhibit anti-tumor function, while reducing the anti-inflammatory macrophages. Moreover, CD47 blockade not only increased the number of intratumoral CD8 + T cells, but also remodeled the T cell cluster toward a more activated one. Further, combination therapy targeting both CD47 and PD-L1 resulted in synergistic inhibition of PDAC growth in the MPC-83 but not in Panc02 model. MPC-83 but not Panc02 mice treated with both anti-CD47 and anti-PD-L1 showed increased number of PD-1 + CD8 + T cells and enhanced expression of key immune activating genes. Conclusion Our data indicate that CD47 targeting induces compartmental remodeling of tumor-infiltrating immune cells of the TME in PDAC. Different PDAC mouse models exhibited differential response to the anti-CD47 and anti-PD-L1 blockade due to the differential effect of this combination treatment on the infiltrating immune cells and key immune activating genes in the TME established by the different PDAC cell lines.
Response by Prysyazhna et al to Letter Regarding Article, “Blood Pressure–Lowering by the Antioxidant Resveratrol Is Counterintuitively Mediated by Oxidation of cGMP-Dependent Protein Kinase”
Authors: Oleksandra Prysyazhna, Kathryn Wolhuter, Christopher Switzer, Celio Santos, Xiaoping Yang, Steven Lynham, Ajay M. Shah, Philip Eaton, Joseph R. Burgoyne
Journal: Circulation (2019)
Proteometabolomics of Melphalan Resistance in Multiple Myeloma
Authors: David C. Koomen, Joy D. Guingab, Paula S. Oliveira, Bin Fang, Min Liu, Eric A. Welsh, Mark B. Meads, Tuan Nguyen, Laurel E. Meke, Steven A. Eschrich, Timothy J. Garrett, John M. Koomen, Kenneth H. Shain
Journal: Blood (2018)
A Predictive Model for Early Death after Frontline Hypomethylating Agents in Elderly Unfit Acute Myeloid Leukemia Patients: Results from the Pethema Group
Authors: Fernando Ramos, David Martinez-Cuadron, Josefina Serrano, Maria Lopez-Pavia, Marta Fuertes-Nuñez, Teresa Bernal, Juan Ignacio Rodriguez-Gutierrez, Isabel Recio, Ana Garrido, Daniel Garcia, Claudia Lucia Sossa, Cristina Gil, Rosario Varela, Pilar Martinez-Sanchez, Maria Angeles Foncillas, Mar Tormo, Antonia Cladera, Graca Esteves, José F. Falantes, Adolfo de la Fuente, Blanca Boluda, Miguel A. Sanz, Pau Montesinos Fernandez
Journal: Blood (2019)
Hypofractionated radiotherapy for pulmonary metastases from hepatocellular carcinoma: Treatment response and prognostic factors affecting survival
Authors: I.Y. Jo, M.-S. Kim, J.S. Seong, J.W. Kim, H.C. Park, T.H. Kim, J.H. Lee, W.S. Yoon, Y.H. Lee, C.-S. Kay
Journal: Annals of Oncology (2019)
Utilization and Early Discontinuation of First-Line Ibrutinib for Patients with Chronic Lymphocytic Leukemia Treated in the Community Oncology Setting in the United States
Authors: Scott F. Huntington, Pamela R. Soulos, Paul M. Barr, Ryan Jacobs, Frederick Lansigan, Oreofe O. Odejide, Lee S. Schwartzberg, Amy J. Davidoff, Cary P Gross
Journal: Blood (2019)
Incidence of Macular Atrophy after Untreated Neovascular Age-Related Macular Degeneration
Authors: Panos G. Christakis, Elvira Agrón, Michael L. Klein, Traci E. Clemons, J. Peter Campbell, Frederick L. Ferris, Emily Y. Chew, Tiarnan D. Keenan
Journal: Ophthalmology (2019)
Association of Adverse Hearing, Growth, and Discharge Age Outcomes With Postnatal Cytomegalovirus Infection in Infants With Very Low Birth Weight
Authors: Kristin E. D. Weimer, Matthew S. Kelly, Sallie R. Permar, Reese H. Clark, Rachel G. Greenberg
Journal: JAMA Pediatrics (2019)

<h3>Importance</h3> Studies suggest that postnatal cytomegalovirus (CMV) infection can lead to long-term morbidity in infants with very low birth weight (VLBW; &lt;1500 g), including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and neurodevelopmental impairment. However, to date, the association of postnatal CMV with hearing, growth, and length of stay among VLBW infants is unknown. <h3>Objectives</h3> To determine the risk for failed hearing screen, increased postnatal age at discharge, or decreased growth at discharge in VLBW infants with postnatal CMV infection compared with CMV-uninfected infants and to compare the risk for other major outcomes of prematurity, including BPD and NEC, in infants with and without postnatal CMV infection. <h3>Participants</h3> This multicenter retrospective cohort study included VLBW infants from 302 neonatal intensive care units managed by the Pediatrix Medical Group from January 1, 2002, through December 31, 2016. Infants hospitalized on postnatal day 21 with a diagnosis of postnatal CMV and hearing screen results after a postmenstrual age of 34 weeks were included in the study population. Data were analyzed from December 11, 2017, to June 14, 2019. <h3>Main Outcomes and Measures</h3> Infants with and without postnatal CMV infection were matched using propensity scores. Poisson and linear regression were used to examine the association between postnatal CMV and the risk of failed hearing screen, postnatal age at discharge, growth, BPD, and NEC. <h3>Results</h3> A total of 304 infants with postnatal CMV were identified, and 273 of these infants (89.8%; 155 boys [56.8%]) were matched with 273 infants without postnatal CMV (148 boys [54.2%]). Hearing screen failure occurred in 45 of 273 infants (16.5%) with postnatal CMV compared with 25 of 273 infants (9.2%) without postnatal CMV (risk ratio [RR], 1.80; 95% CI, 1.14 to 2.85;<i>P</i> = .01). Postnatal CMV was also associated with an increased postnatal age at discharge of 11.89 days (95% CI, 6.72 to 17.06 days;<i>P</i> &lt; .001) and lower weight-for-age<i>z</i>score (−0.23; 95% CI, −0.39 to −0.07;<i>P</i> = .005). Analysis confirmed an increased risk of BPD (RR, 1.30; 95% CI, 1.17 to 1.44;<i>P</i> &lt; .001), previously reported on infants from this cohort from 1997 to 2012, but not an increased risk of NEC after postnatal day 21 (RR, 2.00; 95% CI, 0.18 to 22.06;<i>P</i> = .57). <h3>Conclusions and Relevance</h3> These data suggest that postnatal CMV infection is associated with lasting sequelae in the hearing and growth status of VLBW infants and with prolonged hospitalization. Prospective studies are needed to determine the full effects of postnatal CMV infection and whether antiviral treatment reduces the associated morbidity.
Induction of labour at 41 weeks versus expectant management and induction of labour at 42 weeks (SWEdish Post-term Induction Study, SWEPIS): multicentre, open label, randomised, superiority trial
Authors: Ulla-Britt Wennerholm, Sissel Saltvedt, Anna Wessberg, Mårten Alkmark, Christina Bergh, Sophia Brismar Wendel, Helena Fadl, Maria Jonsson, Lars Ladfors, Verena Sengpiel, Jan Wesström, Göran Wennergren, Anna-Karin Wikström, Helen Elden, Olof Stephansson, Henrik Hagberg
Journal: BMJ (2019)

To evaluate if induction of labour at 41 weeks improves perinatal and maternal outcomes in women with a low risk pregnancy compared with expectant management and induction of labour at 42 weeks.Multicentre, open label, randomised controlled superiority trial.14 hospitals in Sweden, 2016-18.2760 women with a low risk uncomplicated singleton pregnancy randomised (1:1) by the Swedish Pregnancy Register. 1381 women were assigned to the induction group and 1379 were assigned to the expectant management group.Induction of labour at 41 weeks and expectant management and induction of labour at 42 weeks.The primary outcome was a composite perinatal outcome including one or more of stillbirth, neonatal mortality, Apgar score less than 7 at five minutes, pH less than 7.00 or metabolic acidosis (pH <7.05 and base deficit >12 mmol/L) in the umbilical artery, hypoxic ischaemic encephalopathy, intracranial haemorrhage, convulsions, meconium aspiration syndrome, mechanical ventilation within 72 hours, or obstetric brachial plexus injury. Primary analysis was by intention to treat.The study was stopped early owing to a significantly higher rate of perinatal mortality in the expectant management group. The composite primary perinatal outcome did not differ between the groups: 2.4% (33/1381) in the induction group and 2.2% (31/1379) in the expectant management group (relative risk 1.06, 95% confidence interval 0.65 to 1.73; P=0.90). No perinatal deaths occurred in the induction group but six (five stillbirths and one early neonatal death) occurred in the expectant management group (P=0.03). The proportion of caesarean delivery, instrumental vaginal delivery, or any major maternal morbidity did not differ between the groups.This study comparing induction of labour at 41 weeks with expectant management and induction at 42 weeks does not show any significant difference in the primary composite adverse perinatal outcome. However, a reduction of the secondary outcome perinatal mortality is observed without increasing adverse maternal outcomes. Although these results should be interpreted cautiously, induction of labour ought to be offered to women no later than at 41 weeks and could be one (of few) interventions that reduces the rate of stillbirths.Current Controlled Trials ISRCTN26113652.
End-of-life palliative care resource utilization in cancer care: A focus on the urban-rural continuum.
Authors: Jessica Cerni, Joel Rhee, Hassan Hosseinzadeh
Journal: Journal of Clinical Oncology (2019)

52 Background: Despite the advances in end-of-life cancer care, disparities exist in the availability, accessibility and use of palliative care services across the urban-rural continuum. This review explores this disparity by synthesising retrospective quantitative studies on palliative care patterns of resource use for adults during end-of-life cancer care. Methods: Five databases were searched and data analysed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria involved; a) original research; b) quantitative studies; c) English-language; d) study assessed palliative care related service use in adult (18yrs+) cancer patients with any malignancy excluding non-melanoma skin cancer; e) exclusive end of life focus and f) urban-rural focus. Narrative reviews and discussions were excluded. Results: After reviewing all titles and abstracts ( N= 816) and full text review ( N= 163) 44 studies met the inclusion criteria and were included in the analysis. End-of-life palliative care access and utilisation patterns varied across the geographical urban-rural continuum. Geographical region of residence had the strongest association with multiple ED visits and hospitalizations in rural or remote areas. Most common palliative care services used within the last 30 days of death were ED visits and hospital admissions. Two studies assessed palliative radiotherapy and one study assessed palliative care pharmacotherapy. The odds of palliative service use were lowest for males and individuals with a survival diagnosis (0-3months). The largest inequities were explained by individual level factors including gender as assessed in ( N= 44 studies), socioeconomic status ( N= 15), proximity to service ( N= 10) and survival time from cancer diagnosis ( N= 9). Conclusions: Rurality was an important predictor for poorer outcomes in the quality of end-of-life cancer care. Findings suggest that addressing the urban-rural continuum is critical for equitable, timely and efficient palliative cancer care. Further research is required to understand barriers to service usage to achieve optimal palliative care.
Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia: Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age
Authors: Cecilie U. Rank, Benjamin O. Wolthers, Kathrine Grell, Birgitte K. Albertsen, Thomas L. Frandsen, Ulrik M. Overgaard, Nina Toft, Ove J. Nielsen, Peder S. Wehner, Arja Harila-Saari, Mats M. Heyman, Johan Malmros, Jonas Abrahamsson, Ulrika Norén-Nyström, Beata Tomaszewska-Toporska, Bendik Lund, Kirsten B. Jarvis, Petter Quist-Paulsen, Goda E. Vaitkevičienė, Laimonas Griškevičius, Mervi Taskinen, Ulla Wartiovaara-Kautto, Kristi Lepik, Mari Punab, Ólafur G. Jónsson, Kjeld Schmiegelow
Journal: Journal of Clinical Oncology (2019)

PURPOSE Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored. PATIENTS AND METHODS We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. RESULTS Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95% CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0% for children (1.0-9.9 years: 95% CI, 5.4 to 8.6), 10.1% for adolescents (10.0 to 17.9 years: 95% CI, 7.0 to 13.3), and 11.0% for adults (18.0-45.9 years: 95% CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95% CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95% CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95% CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse. CONCLUSION Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse.
Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): our past twenty years
Authors: Chunlin Zhuang, Christophe Pannecouque, Erik De Clercq, Fener Chen
Journal: Acta Pharmaceutica Sinica B (2019)

Human immunodeficiency virus (HIV) is the primary infectious agent of acquired immunodeficiency syndrome (AIDS), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are the cornerstone of HIV treatment. In the last 20 years, our medicinal chemistry group has made great strides in developing several distinct novel NNRTIs, including 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), thio-dihydro-alkoxy-benzyl-oxopyrimidine (S-DABO), diaryltriazine (DATA), diarylpyrimidine (DAPY) analogues, and their hybrid derivatives. Application of integrated modern medicinal strategies, including structure-based drug design, fragment-based optimization, scaffold/fragment hopping, molecular/fragment hybridization, and bioisosterism, led to the development of several highly potent analogues for further evaluations. In this paper, we review the development of NNRTIs in the last two decades using the above optimization strategies, including their structure–activity relationships, molecular modeling, and their binding modes with HIV-1 reverse transcriptase (RT). Future directions and perspectives on the design and associated challenges are also discussed.
Validation of BCL11A As Therapeutic Target in Sickle Cell Disease: Results from the Adult Cohort of a Pilot/Feasibility Gene Therapy Trial Inducing Sustained Expression of Fetal Hemoglobin Using Post-Transcriptional Gene Silencing
Authors: Erica B. Esrick, Maureen Achebe, Myriam Armant, Pablo Bartolucci, Marioara Felicia Ciuculescu, Heather Daley, Colleen Dansereau, Giuseppe Di Caprio, Bronner Goncalves, Nicolas Hebert, Matthew M Heeney, John M. Higgins, Leslie E. Lehmann, John P Manis, Olivier Negre, Sarah Nikiforow, Ethan Schonbrun, David K. Wood, David A. Williams
Journal: Blood (2019)
Acute hypoxia reduces exogenous glucose oxidation, glucose turnover, and metabolic clearance rate during steady-state aerobic exercise
Authors: Lee M. Margolis, Marques A. Wilson, Claire C. Whitney, Christopher T. Carrigan, Nancy E. Murphy, Patrick N. Radcliffe, Jess A. Gwin, David D. Church, Robert R. Wolfe, Arny A. Ferrando, Andrew J. Young, Stefan M. Pasiakos
Journal: Metabolism (2019)
Hypertension in Patients Treated With Ibrutinib for Chronic Lymphocytic Leukemia
Authors: Lindsey E. Roeker, Maryam Sarraf Yazdy, Joanna Rhodes, Julie Goodfriend, Mayur Narkhede, Joseph Carver, Anthony Mato
Journal: JAMA Network Open (2019)

This cohort study describes patterns of development, management strategies, and long-term vascular consequences of hypertension associated with ibrutinib in the non–clinical trial setting.
Eltrombopag Creates a Transient Chemical Phenocopy of TET2 Loss of Function That Contributes to Hematopoietic Precursor Expansion
Authors: Yihong Guan, Bhumika J. Patel, Metis Hasipek, Dale Grabowski, Hassan Awada, Cassandra M Kerr, Valeria Visconte, Aziz Nazha, Yogenthiran Saunthararajah, Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Babal K. Jha
Journal: Blood (2019)
A phase II single arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated Classical Kaposi Sarcoma (CKS)
Authors: A. Zer, O. Icht, O. Jacobi, E. Fenig, S. Shamai, O. Merimsky, R. Shapira, H. Bernstine, R. Weitzen, O. Vornikova, E. Ben-Ami, G. Bar-Sela, S.M. Stemmer, M. Lotem
Journal: Annals of Oncology (2019)
A Renewed Focus on Youth Substance Use Prevention Is Needed Among Health Care Professionals and Families
Authors: Robert L. DuPont, Caroline DuPont
Journal: JAMA Network Open (2019)

Bertha K. Madras, PhD; Beth Han, MD, PhD, MPH; Wilson M. Compton, MD, MPE; Christopher M. Jones, PharmD, DrPH, MPH; Elizabeth I. Lopez, PhD; Elinore F. McCance-Katz, MD, PhD
Cumulative Blood Pressure Exposure During Young Adulthood and Mobility and Cognitive Function in Midlife
Authors: Simin Mahinrad, Shawn Kurian, Chaney R. Garner, Sanaz Sedaghat, Alexander J. Nemeth, Nicola Moscufo, James P. Higgins, David R. Jacobs, Jeffrey M. Hausdorff, Donald M. Lloyd-Jones, Farzaneh A. Sorond
Journal: Circulation (2019)

High blood pressure (BP) is a known risk factor for mobility and cognitive impairment in older adults. This study tested the association of cumulative BP exposure from young adulthood to midlife with gait and cognitive function in midlife. Furthermore, we tested whether these associations were modified by cerebral white matter hyperintensity (WMH) burden.We included 191 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults), a community-based cohort of young individuals followed over 30 years. Cumulative BP was calculated as the area under the curve (mm Hg×years) from baseline up to year 30 examination. Gait and cognition were assessed at the year 30 examination. Cerebral WMH was available at year 30 in a subset of participants (n=144) who underwent magnetic resonance imaging. Multiple linear regression models were used to assess the association of cumulative BP exposure with gait and cognition. To test effect modification by WMH burden, participants were stratified at the median of WMH and tested for interaction.Higher cumulative systolic and diastolic BPs were associated with slower walking speed (both P=0.010), smaller step length (P=0.011 and 0.005, respectively), and higher gait variability (P=0.018 and 0.001, respectively). Higher cumulative systolic BP was associated with lower cognitive performance in the executive (P=0.021), memory (P=0.015), and global domains (P=0.010), and higher cumulative diastolic BP was associated with lower cognitive performance in the memory domain (P=0.012). All associations were independent of socio-demographics and vascular risk factors (body mass index, smoking, diabetes mellitus and total cholesterol). The association between cumulative BP and gait was moderated by WMH burden (interaction P<0.05). However, the relation between cumulative BP and cognitive function was not different based on the WMH burden (interaction P>0.05).Exposure to higher BP levels from young to midlife is associated with worse gait and cognitive performance in midlife. Furthermore, WMH moderates the association of cumulative BP exposure with gait, but not with cognitive function in midlife. The mechanisms underpinning the impact of BP exposure on brain structure and function must be investigated in longitudinal studies using a life course approach.
Severe hypovitaminosis D in metastatic gastric cancer patients from the Northern and Southern hemispheres: Data from the EXPAND phase III trial
Authors: R. Obermannova, D. Valik, D. Hasenclever, L. Zdrazilova-Dubska, U. Hacker, R. Demlova, I. Selingerova, F. Lordick
Journal: Annals of Oncology (2019)