tbuckley/cabot-search huggingface dataset:
Evaluation of febrile neutropenia and myelosuppression in patients receiving FOLFOX/FOLFIRI in gastrointestinal cancer treated with same-day (SD) pegfilgrastim/pegfilgrastim-CBQV (PFG).
Authors: Basel Shoua, Mahta Mahmoudieh, Aaron James Scott, Jerrelee Hollings, Rachna T. Shroff, Ali McBride
Journal: Journal of Clinical Oncology (2021)

311 Background: The National Comprehensive Cancer Network (NCCN) guidelines and the manufacturers of PFG recommend administration at least 24 hours after chemotherapy (CTX). Administering SD PFG carries the potential risk for exacerbation of neutropenia based on analyses in lymphoma and breast cancer regimens; however, little data exists on infusional fluorouracil and SD PFG administration. The availability of biosimilar PFG and increased utilization of growth factors during the COVID-19 pandemic has led to changes in practice for SD PFG administration. This study explored the incidence of febrile neutropenia (FN) and myelosuppression with FOLFOX and FOLFIRI regimens in Gastrointestinal malignancies (GI) to address the safety of SD utilization of PFG. Methods: Patient data was extracted through electronic health records search of ICD-9 and ICD-10 codes for GI malignancies and treated with FOLFOX or FOLFIRI-based regimens from November 2013 to May 2021. SD administration was defined as administration of PFG within 15 minutes after fluorouracil pump disconnect. The primary endpoint of our study was to evaluate the incidence of FN across all CTX cycles for up to four cycles, in SD PFG administration. Secondary outcomes included chemotherapy induced neutropenia (CIN), hospitalizations, and CTX dose reduction or delay. Results: Three hundred and thirty-nine patient charts were reviewed with 55 patients meeting the inclusion criteria. In our study cohort, 72.7% received FOLFOX and 27.2% received FOLFIRI-based regimens. Out of all 194 CTX cycles, 136 (70.1%) cycles received pegfilgrastim and 58 cycles received pegfilgrastim-cbqv (29.9%). Two patients had grade 3/4 CIN (1%), with both cases resulting in FN (1%). Both FN cases resulted in hospitalizations, and dose delays or reductions. Investigation of FN incidences revealed that both patients received CTX with active infections, one case with a urinary tract infection and the other with a chronic gangrene infection. Conclusions: Our study results suggest that SD administration of PFG can be as a safe and effective alternative to 24-hour post-chemotherapy administration in patients receiving FOLFOX or FOLFIRI-based regimens. The incidence of FN was noted to be minimal in our study. Furthermore, no noted increase in myelosuppression was seen in our analysis, as compared to previous studies in breast cancer and lymphoma-based regimens. SD administration not only minimizes travel burdens on long-distance patients but also has allowed for reduction in infusion appointments and therefore possible exposure to the SARS-COV2 virus during the 2020-2021 pandemic. Future prospective studies are warranted in order to elucidate the risk of FN and myelosuppression in patients undergoing chemotherapy for GI malignancies with SD PFG administration.
Impact of anti-CD20 monoclonal antibodies on serologic response to BNT162b2 vaccine in B-cell Non-Hodgkin’s lymphomas
Authors: Francesco Marchesi, Fulvia Pimpinelli, Diana Giannarelli, Livia Ronchetti, Elena Papa, Paolo Falcucci, Martina Pontone, Enea Gino Di Domenico, Simona di Martino, Valentina Laquintana, Chiara Mandoj, Laura Conti, Iole Cordone, Antonia La Malfa, Caterina Viggiani, Daniela Renzi, Francesca Palombi, Atelda Romano, Francesco Pisani, Svitlana Gumenyuk, Ornella Di Bella, Branka Vujovic, Aldo Morrone, Gennaro Ciliberto, Fabrizio Ensoli, Andrea Mengarelli
Journal: Leukemia (2021)
Stereotactic ablative radiotherapy for operable stage I non-small-cell lung cancer (revised STARS): long-term results of a single-arm, prospective trial with prespecified comparison to surgery
Authors: Joe Y Chang, Reza J Mehran, Lei Feng, Vivek Verma, Zhongxing Liao, James W Welsh, Steven H Lin, Michael S O'Reilly, Melenda D Jeter, Peter A Balter, Stephen E McRae, Donald Berry, John V Heymach, Jack A Roth, Mara Antonoff, Wayne Hofstetter, Ravi Rajaram, David Rice, Boris Sepesi, Stephen Swisher, Ara Vaporciyan, Garrett Walsh, Craig DeGraaf, Arlene Correa, Aileen Chen, Saumil Gandhi, Ritsuko Komaki, Percy Lee, Quynh-Nhu Nguyen, Matthew Ning, Song Gao, Julianne Pollard-Larkin, Paige Nitsch, Ramaswamy Sadagopan, Xiaochun Wang
Journal: The Lancet Oncology (2021)
Oncostatin M regulates hematopoietic stem cell (HSC) niches in the bone marrow to restrict HSC mobilization
Authors: Kavita Bisht, Crystal McGirr, Seo-Youn Lee, Hsu-Wen Tseng, Whitney Fleming, Kylie A. Alexander, Taichi Matsumoto, Valérie Barbier, Natalie A. Sims, Gerhard Müller-Newen, Ingrid G. Winkler, Halvard Bonig, Jean-Pierre Lévesque
Journal: Leukemia (2021)
OS05.2.A <i>MGMT</i> promoter status in <i>IDH1/2</i> mutant anaplastic astrocytoma patients assessed by DNA methylation profiling and qMS-PCR: a report from the EORTC Brain Tumor Group
Authors: C M S Tesileanu, P J French, M Sanson, A A Brandes, W Wick, P M Clement, J M Kros, T Gorlia, V Golfinopoulos, M J van den Bent
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Temozolomide (TMZ) efficacy in high-grade glioma is related to O 6-methylguanine DNA methyltransferase promoter (MGMTp) methylation. We compared the prognostic and predictive effect of MGMTp between DNA methylation profiling (the MGMT-STP27 model) and quantitative methylation specific polymerase chain reaction (qMS-PCR) in isocitrate dehydrogenase 1 and 2 (IDH1/2) mutant (mt) anaplastic astrocytoma patients. MATERIAL AND METHODS The 2x2 factorial design phase III CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4 Gy radiotherapy (RT), RT with concurrent TMZ, RT with 12 cycles of adjuvant TMZ, or RT with concurrent and adjuvant TMZ. MGMTp methylation status was assessed with the MGMT-STP27 model using 850k EPIC data, and qMS-PCR. IDH1/2 mutation status was determined with a next-generation sequencing panel. Overall survival (OS) was measured from date of randomization. RESULTS We identified 444 IDH1/2mt anaplastic astrocytoma patients of which MGMT-STP27 data was available for 440 patients (99.1%), qMS-PCR data for 361 patients (81.3%), and both for 357 patients (80.4%). MGMTp was methylated in 365 patients (83.0%) for the MGMT-STP27 model, and 168 patients (46.5%) for qMS-PCR. The agreement between the MGMT-STP27 model and qMS-PCR is 59.9% with a Cohen’s Kappa score of 0.229. At database lock, 289 patients with MGMT-STP27 data were still alive and 236 patients with qMS-PCR data. The median OS of MGMTp methylated glioma patients was 9.1 yrs [95 % confidence interval (CI) 7.5-not reached] for the MGMT-STP27 model, and not reached [95 % CI 9.1-not reached] for the qMS-PCR data. For MGMTp unmethylated glioma patients, the median OS was 6.9 yrs [95% CI 6.2-not reached] for the MGMT-STP27 model, and 6.8 yrs [95% CI 6.2–9.7] for the qMS-PCR data. The hazard ratio (HR) for OS based on MGMTp methylation was 0.88 [95% CI 0.58–1.31] for the MGMT-STP27 data, and 0.72 [95% CI 0.50–1.03]) for the qMS-PCR data. The HR for OS after RT with any TMZ vs RT alone for the MGMT-STP27 model was 0.53 [95% CI 0.37–0.78] for MGMTp methylated, and 0.54 [95% CI 0.25–1.18] for MGMTp unmethylated glioma patients; and for the MS-PCR data was 0.34 [95% CI 0.19–0.61] for MGMTp methylated, and 0.53 [95% CI 0.33–0.85] for MGMTp unmethylated glioma patients. CONCLUSION MGMTp methylation, regardless of assay, was neither prognostic nor predictive for outcome to temozolomide in IDH1/2mt anaplastic astrocytoma patients.
Opioid overdose deaths before, during, and after an 11-week COVID-19 stay-at-home order - Cook County, Illinois, January 1, 2018-October 6, 2020
Authors: M. Mason, S. B. Welch, Ponni, Arunkumar, Post, L. A., J. M. Feinglass
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

This article provides estimates of the opioid-related fatal overdoses in Cook County in Illinois before, during, and after a stay-at-home order was lifted. During the 99-week period from 1 January, 2018, to 6 October, 2020, a total of 3,843 people died in Cook County due to opioid overdoses. The spike in deaths during the last 16 weeks of 2019 followed an increase of almost 10% in the previous 16 weeks. It is possible that the increase in opioid overdose deaths during the stay-at-home period was a continuation of the increases that occurred in the 16 weeks before the order was lifted. Although the mean deaths declined during the period after the order, they still remained elevated above pre-2020 levels. It might indicate a persistent upward trend in the number of overdose deaths reported by the Centers for Disease Control and Prevention (CDC). Since the outbreak of COVID-19, various outreach, treatment, recovery, and education initiatives have been implemented to prevent drug-related deaths.
A comprehensive review on the lipid and pleiotropic effects of pitavastatin
Authors: Amirhossein Sahebkar, Nasim Kiaie, Armita Mahdavi Gorabi, Massimo R. Mannarino, Vanessa Bianconi, Tannaz Jamialahmadi, Matteo Pirro, Maciej Banach
Journal: Progress in Lipid Research (2021)
Methods to Address Confounding and Other Biases in Meta-Analyses: Review and Recommendations
Authors: Maya B. Mathur, Tyler J. VanderWeele
Journal: Annual Review of Public Health (2021)

Meta-analyses contribute critically to cumulative science, but they can produce misleading conclusions if their constituent primary studies are biased, for example by unmeasured confounding in nonrandomized studies. We provide practical guidance on how meta-analysts can address confounding and other biases that affect studies' internal validity, focusing primarily on sensitivity analyses that help quantify how biased the meta-analysis estimates might be. We review a number of sensitivity analysis methods to do so, especially recent developments that are straightforward to implement and interpret and that use somewhat less stringent statistical assumptions than do earlier methods. We give recommendations for how these newer methods could be applied in practice and illustrate using a previously published meta-analysis. Sensitivity analyses can provide informative quantitative summaries of evidence strength, and we suggest reporting them routinely in meta-analyses of potentially biased studies. This recommendation in no way diminishes the importance of defining study eligibility criteria that reduce bias and of characterizing studies' risks of bias qualitatively.
Nuclear speckle specific hnRNP D-like prevents age- and AD-related cognitive decline by modulating RNA splicing
Authors: Qingyang Zhang, Juan Zhang, Jin Ye, Xiaohui Li, Hongda Liu, Xiaolin Ma, Chao Wang, Keqiang He, Wei Zhang, Ji Yuan, Yingjun Zhao, Huaxi Xu, Qiang Liu
Journal: Molecular Neurodegeneration (2021)

Abstract Background Aberrant alternative splicing plays critical role in aging and age-related diseases. Heterogeneous nuclear ribonucleoproteins (hnRNPs) reportedly regulate RNA splicing process. Whether and how hnRNPs contribute to age-related neurodegenerative diseases, especially Alzheimer’s disease (AD), remain elusive. Methods Immunoblotting and immunostaining were performed to determine expression patterns and cellular/subcellular localization of the long isoform of hnRNP D-like (L-DL), which is a hnRNP family member, in mouse hippocampus. Downregulation of L-DL in WT mice was achieved by AAV-mediated shRNA delivery, followed by memory-related behavioural tests. L-DL interactome was analysed by affinity-precipitation and mass spectrometry. Alternative RNA splicing was measured by RNA-seq and analyzed by bioinformatics-based approaches. Downregulation and upregulation of L-DL in APP/PS1 mice were performed using AAV-mediated transduction. Results We show that L-DL is specifically localized to nuclear speckles. L-DL levels are decreased in the hippocampus of aged mouse brains and downregulation of L-DL impairs cognition in mice. L-DL serves as a structural component to recruit other speckle proteins, and regulates cytoskeleton- and synapse-related gene expression by altering RNA splicing. Mechanistically, these splicing changes are modulated via L-DL-mediated interaction of SF3B3, a core component of U2 snRNP, and U2AF65, a U2 spliceosome protein that guides U2 snRNP’s binding to RNA. In addition, L-DL levels are decreased in APP/PS1 mouse brains. While downregulation of L-DL deteriorates memory deficits and overexpression of L-DL improves cognitive function in AD mice, by regulating the alternative splicing and expression of synaptic gene CAMKV . Conclusions Our findings define a molecular mechanism by which hnRNP L-DL regulates alternative RNA splicing, and establish a direct role for L-DL in AD-related synaptic dysfunction and memory decline.
P12.03 A Delphi survey to inform core ‘red flag’ symptoms for an electronic patient reported outcome system in glioblastoma follow up
Authors: A Luis, F Boele, T Booth
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastoma is a common and aggressive primary malignant brain tumour in adults associated with a poor prognosis and considerable symptom burden. Clinical review and serial neuroimaging remain the primary monitoring tools to assess for disease status. However, the evidence base for the existing surveillance imaging schedule is yet to be established. New models of follow up care are needed to demonstrate better patient outcomes in this patient cohort. There are indications that patient-reported outcome measures (PROMs) can contribute to improved survival and maintaining an optimal quality of life in other oncology populations. MATERIALS AND METHODS There are no standardised PROMs for the priority symptoms in glioblastoma patients, which can be used for evaluation in clinical care as a surrogate marker for disease progression. A broad set of symptoms were therefore initially identified in a targeted literature search and were further refined via Delphi methodology, with the aim to obtain consensus amongst a small expert panel involved in the care of glioblastoma patients. A three round Delphi email survey was conducted. Consensus was defined as 70% agreement. RESULTS Symptom and function constructs were assessed for relevance, relationship to disease and treatment, sensitivity to change, psychometric properties and patient acceptability. Consensus was reached on the red flag symptoms and symptom clusters to monitor, as well as the minimum severity thresholds needed to trigger an alert on an electronic symptom reporting system, which has been developed to allow patient self-reporting of symptoms during treatment. CONCLUSION The red flag symptoms to monitor, along with the symptom severity thresholds, informed an app-based symptom reporting system, which is currently being piloted in a feasibility study exploring triggered imaging using ePROMs. This has the potential to inform future clinical practice through development of patient reported biomarkers.
2007년 대한간학회 학술연구기금 당선과제 발표 : 라미부딘 내성 만성B형간염환자에서 아데포비어/엔테카비어 연속 치료 시 라미부딘 내성 rtM204변이 형태, precore/core promoter변이 동반 여부에 따른 바이러스의 선택과 축적 양상
Authors: 송병철, 박능화, 신정우
Journal: Clinical and Molecular Hepatology (2007)
Evaluation of real-world cost savings and utilization of biosimilar drugs in a community-based oncology practice.
Authors: Amit Sanyal, Michelle Schmitt, Daniel Wellner
Journal: Journal of Clinical Oncology (2021)

73 Background: Biosimilar drugs, defined as biologic products with no clinically significant differences in quality, efficacy and safety compared to approved reference products have gained increasing adoption based on studies projecting significant cost savings[1]. Real world evaluation of biosimilar related cost savings and adoption is however still limited. We prospectively evaluate cost savings generated by transitioning to biosimilar monoclonal antibodies in a community based oncology practice. Methods: In July 2020, a process for transitioning patients to biosimilar equivalents of Rituximab, Trastuzumab and Bevacizumab was implemented in a community based oncology practice. Provider adoption was facilitated by monthly oncology pharmacy governance meetings that allowed provider participation and feedback followed by defaulting the preferred biosimilar product in oncology chemotherapy software (Epic Beacon, Epic Systems, Verona, WI). The treatment templates allowed for care personalization by listing reference products that could be chosen if desired. Cost savings achieved by switching to biosimilars was calculated by subtracting the actual spending on the biosimilar product from projected acquisition cost of the branded reference product (Table). Biosimilar adoption, defined as amount of biosimilar drug used over total amount of the drug ordered was also calculated. Results: Between July 2020 and April 2021, transitioning to biosimilar products for Rituximab, Bevacizumab and Trastuzumab resulted in net savings of $268,194.64, $285,251.89 and $274,359.51 respectively. Actual spending on Rituximab biosimilar product was $726,476.10 against a projected spending of $994,670.74 on the branded reference product. Actual spending on Bevacizumab biosimilar product was $1,254,977.30 against a projected spending of $1,540,229.19 on the branded reference product. Actual spending on Trastuzumab biosimilar product was $1,218,641.60 against a projected spending of $1,493,001.11 on the branded product. Average biosimilar utilization between October 2020 and April 2020 has been 92%, 100% and 98% for Rituximab, Bevacizumab and Trastuzumab respectively. Conclusions: Significant cost-savings can result from widespread utilization of biosimilar drugs in community oncology practices. References: Mulcahy, A.W., J.P. Hlavka, and S.R. Case, Biosimilar Cost Savings in the United States: Initial Experience and Future Potential. Rand Health Q, 2018. 7(4): p. 3.[Table: see text]
The Relation of Blood Platelets to Hemorrhagic Disease
Authors: W. W. Duke
Journal: JAMA (1983)

It is my purpose in this paper to report three cases and experiments which furnish additional evidence to show that the blood platelets play a part in stopping hemorrhage, and that one type of hemorrhagic disease may be attributed to an extreme reduction in the number of platelets. The cases possibly explain the relief which sometimes follows transfusion in hemorrhagic disease. It is my purpose also to describe a method for studying hemorrhage called the bleeding time, and to describe briefly a simple method for determining the coagulation time. In the cases there was marked hemorrhagic diathesis, a normal coagulation time, and almost an absence of platelets. Transfusion was performed in each case. After transfusion there was a marked increase in the number of platelets and remarkable relief of hemorrhage. When the platelet counts returned to their previous low level, hemorrhages returned. Later in the course of the disease in
Abstract 14967: Determinants of Early Diastolic Strain Rate and Its Relation to NT-proBNP in Heart Failure
Authors: Sven-Oliver Troebs, Sören Schwuchow, Mathias Grosch, Sebastian Göbel, Simon Diestelmeier, Andreas Schulz, Tina Herholz, Jaume Lerma Monteverde, Stefanie Steck, Giacomo Viti, Tommaso Gori, Karl J. Lackner, Thomas Münzel, Jürgen Prochaska, Philipp S. Wild
Journal: Circulation (2018)

Background: Early diastolic strain rate(E/DSrE’) is a novel echocardiographic measure of cardiac function. Data on its clinical determinants and its relation to NT-proBNP in heart failure is scarce...
Effects of active cancer treatment on safety and immunogenicity of COVID-19 mRNA-BNT162b2 vaccine: preliminary results from the prospective observational Vax-On study
Authors: F. Nelli, A. Fabbri, A. Onorato, D. Giannarelli, M.A. Silvestri, J.R. Giron Berrios, A. Virtuoso, E. Marrucci, C. Signorelli, M.G. Chilelli, F. Primi, M. Schirripa, M. Mazzotta, E.M. Ruggeri
Journal: Annals of Oncology (2021)
P14.89 Papillary tumor of the pineal region: three cases from a single institution
Authors: F Yorio, I J Ujhelly, B Calabrese, A Cervio, A Muggeri
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Papillary tumors of the pineal region are highly unusual lesions of unknown incidence. These are neuroepithelial tumors with papillary and solid areas. There is no standardized treatment because of the difficulty to make randomized prospective trials due to its rarity. We report three patients with papillary tumor of the pineal region. MATERIAL AND METHODS Retrospective review of the clinical records of patients with papillary tumor of the pineal region at a tertiary neurological center in Buenos Aires, Argentina was done between 2/2012-04/2021. Clinical characteristics, imaging, pathology, treatment and follow-up data were obtained. RESULTS Two patients were male and one female. All three patients were adults, two in the fourth decade of life and one in the seventh. Clinical presentation included headache along with either visual symptoms, gait disturbance, or both. Imaging workup included brain and spinal magnetic resonance imaging, finding expanding lesions in the pineal region, hyperintense in FLAIR/T2 sequences, with gadolinium enhancement in T1 with contrast sequence and variable degrees of hydrocephalus. Spinal lesions were not found in these patients. Cerebrospinal fluid cytology was negative in all cases. Tumor biopsy was the initial approach in all cases. Two patients underwent an initial third ventriculostomy procedure but all were submitted to a supracerebellar infratentorial approach for major resection. Posterior treatment included chemoradiotherapy with temozolomide. One patient had a distant recurrence after seven years with and remained with stable disease for two more years, and the other two patients are under control with no recurrence after 2 and 2.5 years respectively. CONCLUSION Papillary tumors in the pineal regions are aggressively treated as recurrence is very frequent regarding previous reports (&amp;gt; 70%). Total resection is the only predictive factor associated to better outcome, however, more information is needed in order to achieve treatment consensus.