tbuckley/cabot-search huggingface dataset:
Early mortality after resection of locally advanced rectal cancer in elderly United States patients.
Authors: Helmneh M. Sineshaw, K Robin Yabroff, Vassiliki Liana Tsikitis, Ahmedin Jemal, Timur Mitin
Journal: Journal of Clinical Oncology (2019)

11529 Background: Early mortality after resection of locally advanced rectal cancer in patients age 75 and older has not been studied in the United States. This information could inform clinical decision-making for patients who achieve complete clinical response after neoadjuvant therapy and consider watchful waiting versus surgical resection. Methods: Using the National Cancer Data Base, we identified patients age 75 years and older who underwent surgery for clinical stage II or III rectal cancer between 2004-2015. We performed multivariable logistic regression analyses to assess associations between patient and facility characteristics and 30-day, 90-day, and 6-month mortality. Results: Among 11,326 patients, 94% underwent resection and the remaining 6% underwent local excision. Overall early mortality rates after surgery were 4%, 7.6% and 11% for 30-day, 90-day and six-month, respectably. Six-month mortality varied by age subgroup (8% in 75-79 years old to 17.7% in 85 years and older), and comorbidity score (9.5% for comorbidity score = 0 to 18.5% for comorbidity score ≥ 2). Between 2004 and 2015, six-month mortality declined significantly from 11.9% in 2004-2007 to 9.8% in 2012-2015 ( P trend = 0.0029), with the decline larger among patients age 85 years and older (from 19.4% in 2004-2007 to 15.3% in 2012-2015, P trend = 0.0377). In the multivariable analysis, older age, higher comorbidity score, and lower facility case volume were significantly associated with higher odds of six-month mortality. Patients treated at National Cancer Institute (NCI) designated centers had 32% lower odds of six-month mortality compared with those treated at non-NCI designated teaching/research centers. Conclusions: Post-operative six-month mortality among patients age 75 years and older with locally advanced rectal cancer in the US declined steadily over the past decade. Older age, high comorbidity score, and low facility case volume were associated with higher six-month mortality after surgery. Additional efforts are needed to guide elderly patients and their physicians in discussing treatment options for locally advanced rectal cancer.
HIV Rebound Is Predominantly Fueled by Genetically Identical Viral Expansions from Diverse Reservoirs
Authors: Marie-Angélique De Scheerder, Bram Vrancken, Simon Dellicour, Timothy Schlub, Eunok Lee, Wei Shao, Sofie Rutsaert, Chris Verhofstede, Tessa Kerre, Thomas Malfait, Dimitri Hemelsoet, Marc Coppens, Annemieke Dhondt, Danny De Looze, Frank Vermassen, Philippe Lemey, Sarah Palmer, Linos Vandekerckhove
Journal: Cell Host & Microbe (2019)
Enterovirus D68 serosurvey: evidence for endemic circulation in the Netherlands, 2006 to 2016
Authors: Eveliina Karelehto, Gerrit Koen, Kimberley Benschop, Fiona van der Klis, Dasja Pajkrt, Katja Wolthers
Journal: Eurosurveillance (2019)

BackgroundEnterovirus D68 (EV-D68) has caused major outbreaks of severe respiratory illness worldwide since 2010.AimOur aim was to evaluate EV-D68 circulation in the Netherlands by conducting a serosurvey of EV-D68 neutralising antibodies (nAb) among the Dutch general population.MethodsWe screened 280 sera from children and adults in the Netherlands and used two independent sets of samples collected in the years 2006 and 2007 and in the years 2015 and 2016, time points before and after the first EV-D68 upsurge in 2010. Neutralisation capacity of the sera was tested against the prototype Fermon EV-D68 strain isolated in 1962 and against a recent EV-D68 strain (genotype B3) isolated in France in 2016.ResultsRegardless of the time of serum collection, we found remarkably high overall seropositivity (94.3-98.3%) for nAb against both EV-D68 strains. Geometric mean titres increased in an age-dependent manner.ConclusionsOur data suggest that EV-D68 has been circulating in the Netherlands for decades and that the enterovirus surveillance does not accurately capture the prevalence of this clinically relevant pathogen.
Early initiation of breastfeeding and severe illness in the early newborn period: An observational study in rural Bangladesh
Authors: Shahreen Raihana, Michael J. Dibley, Mohammad Masudur Rahman, Tazeen Tahsina, Md. Abu Bakkar Siddique, Qazi Sadequr Rahman, Sajia Islam, Ashraful Alam, Patrick J. Kelly, Shams El Arifeen, Tanvir M Huda
Journal: PLoS Medicine (2019)

In Bangladesh, neonatal sepsis is the cause of 24% of neonatal deaths, over 65% of which occur in the early-newborn stage (0-6 days). Only 50% of newborns in Bangladesh initiated breastfeeding within 1 hour of birth. The mechanism by which early initiation of breastfeeding reduces neonatal deaths is unclear, although the most likely pathway is by decreasing severe illnesses leading to sepsis. This study explores the effect of breastfeeding initiation time on early newborn danger signs and severe illness.We used data from a community-based trial in Bangladesh in which we enrolled pregnant women from 2013 through 2015 covering 30,646 newborns. Severe illness was defined using newborn danger signs reported by The Young Infants Clinical Science Study Group. We categorized the timing of initiation as within 1 hour, 1 to 24 hours, 24 to 48 hours, ≥48 hours of birth, and never breastfed. The analysis includes descriptive statistics, risk attribution, and multivariable mixed-effects logistic regression while adjusting for the clustering effects of the trial design, and maternal/infant characteristics. In total, 29,873 live births had information on breastfeeding among whom 19,914 (66.7%) initiated within 1 hour of birth, and 4,437 (14.8%) neonates had a severe illness by the seventh day after birth. The mean time to initiation was 3.8 hours (SD 16.6 hours). The proportion of children with severe illness increased as the delay in initiation increased from 1 hour (12.0%), 24 hours (15.7%), 48 hours (27.7%), and more than 48 hours (36.7%) after birth. These observations would correspond to a possible reduction by 15.9% (95% CI 13.2-25.9, p < 0.001) of severe illness in a real world population in which all newborns had breastfeeding initiated within 1 hour of birth. Children who initiated after 48 hours (odds ratio [OR] 4.13, 95% CI 3.48-4.89, p < 0.001) and children who never initiated (OR 4.77, 95% CI 3.52-6.47, p < 0.001) had the highest odds of having severe illness. The main limitation of this study is the potential for misclassification because of using mothers' report of newborn danger signs. There could be a potential for recall bias for mothers of newborns who died after being born alive.Breastfeeding initiation within the first hour of birth is significantly associated with severe illness in the early newborn period. Interventions to promote early breastfeeding initiation should be tailored for populations in which newborns are delivered at home by unskilled attendants, the rate of low birth weight (LBW) is high, and postnatal care is limited.Trial Registration number: anzctr.org.au ID ACTRN12612000588897.
Single-Cell Transcriptomic Map of the Human and Mouse Bladders
Authors: Zhenyuan Yu, Jinling Liao, Yang Chen, Chunlin Zou, Haiying Zhang, Jiwen Cheng, Deyun Liu, Tianyu Li, Qingyun Zhang, Jiaping Li, Xiaobo Yang, Yu Ye, Zhiguang Huang, Xinyang Long, Rirong Yang, Zengnan Mo
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Previous studies of bladder cell classification mostly relied on the cell’s morphology, location, electrophysiology, and function. However, it is difficult to classify bladder cells accurately and comprehensively using these methods. The authors created a single-cell transcriptomic map of human bladder cells using single-cell RNA sequencing. They also created a more detailed single-cell sequencing RNA map of the mouse bladder than what was previously available. Using these tools, the authors compare the similarities and differences between human and mouse bladder cells and found many cell types that are highly similar across the two. Additionally, the authors discovered two new types of human bladder cells. One may play a role in allergic reactions and nerve conduction, whereas the other may play a role in bladder emptying. The results may assist scientists studying the relationship between bladder cell types and diseases. Background Having a comprehensive map of the cellular anatomy of the normal human bladder is vital to understanding the cellular origins of benign bladder disease and bladder cancer. Methods We used single-cell RNA sequencing (scRNA-seq) of 12,423 cells from healthy human bladder tissue samples taken from patients with bladder cancer and 12,884 cells from mouse bladders to classify bladder cell types and their underlying functions. Results We created a single-cell transcriptomic map of human and mouse bladders, including 16 clusters of human bladder cells and 15 clusters of mouse bladder cells. The homology and heterogeneity of human and mouse bladder cell types were compared and both conservative and heterogeneous aspects of human and mouse bladder evolution were identified. We also discovered two novel types of human bladder cells. One type is ADRA2A + and HRH2 + interstitial cells which may be associated with nerve conduction and allergic reactions. The other type is TNNT1 + epithelial cells that may be involved with bladder emptying. We verify these TNNT1 + epithelial cells also occur in rat and mouse bladders. Conclusions This transcriptomic map provides a resource for studying bladder cell types, specific cell markers, signaling receptors, and genes that will help us to learn more about the relationship between bladder cell types and diseases.
Clinical characterization of patients with SDHC epimutation in gastrointestinal stromal tumors.
Authors: Maran Ilanchezhian, Sarah N. Fuller, Margarita Raygada, Constantine A. Stratakis, Paul S. Meltzer, Markku Miettinen, John Glod, Keith Killian, Fernanda Irene Arnaldez
Journal: Journal of Clinical Oncology (2019)

11033 Background: Gastrointestinal Stromal Tumors are the most common malignancy in the GI tract. While the vast majority exhibit somatic mutations in KIT and PDGFRA, approximately 15% of GIST patients do not have this feature. This group of KIT and PDGFRA “wildtype” GISTs have in common a negative expression of SDHB when interrogated by immunohistochemistry. Succinate dehydrogenase (SDH) is a conserved enzyme that plays a critical role in cellular metabolism and energy production. A loss in SDH function is a mechanism observed in several types of cancers, and germline SDH mutations are considered a tumor predisposition syndrome. This group has reported that SDH-deficient gastrointestinal stromal tumors often harbor germline mutations in the SDH subunit genes (SDHA, SDHB, SDHC, and SDHD, termed SDHx). There is, however, a defined group that shows lack of SDH expression in the absence of mutation. Methods: We performed targeted exome sequencing on GIST patients’ tumor samples from the NIH GIST clinic and identified 25 SDHx-WT cases. Genome-wide DNA methylation and expression profiling showed SDHC promoter-specific CpG island hypermethylation and gene silencing in these 25 SDHx-WT, SDH deficient GISTs. Results: Clinical characterization of this cohort revealed that 24 of 25 SDHC-epimutant GISTs occurred in female patients, with a median age of 12 upon diagnosis. The median tumor size of this cohort of patients was 4.0 cm. Of the 16 patients from whom we were able to obtain complete pathology data, 15 showed epithelioid or mixed-epithelioid tumor morphology. All of them showed negative immunohistochemical staining for SDHB. 15 of 16 patients had multifocal tumors, which is a common finding in this population. Conclusions: The profiling of this cohort provides further insights into the natural history and pathogenesis of SDHC-epimutant GIST tumors.
From presentation to paper: Gender disparities in oncological research.
Authors: Willemieke P.M. Dijksterhuis, Charlotte I. Stroes, Wan Ling Tan, Suthinee Ithimakin, Antonio Calles, Jorge Barriuso, Sjoukje Oosting, Daniela Kolarevic, Andrew J.S. Furness, Ivana Bozovic, Carlos Alberto Gomez-Roca, Hanneke W.M. Van Laarhoven
Journal: Journal of Clinical Oncology (2019)

10523 Background: Gender discrepancies have been identified in authorships of scientific publications, grant applications, and peer review in many disciplines, including oncology. The exact share of women presenting results of oncological studies at large conferences is unknown, while the oral presentation of a study at such a podium enhances the international visibility and recognition of the presenting person. Therefore, we aim to identify gender-based differences in contributions to presentations at two major oncological conferences. Methods: We collected consecutive abstracts presented at the plenary sessions of the American Society of Clinical Oncology (ASCO) Annual Meetings and presidential sessions of the European Society for Medical Oncology (ESMO) Congresses. Sex of the presenters and abstract authors, study results (positive vs. negative), and subsequently published papers were identified. Chi square tests were used to compare the distribution of sex over time. The association between presenter’s or last author’s sex and study outcome and impact factors were analyzed using Chi square tests and Mann-Whitney U tests, respectively. Results: Of available abstracts presented at ASCO between 2011 and 2018 (N = 34), and ESMO between 2008 and 2018 (N = 132), presenters were female in 24% and 21%, respectively. Female last authors were seen in 21% and 20% of these ASCO and ESMO abstracts. Of all contributing authors to these ASCO (N = 569) and ESMO (N = 1851) abstracts, 31% and 27% were female, respectively. The distribution of male and female ASCO and ESMO presenters (P = 0.580, P = 0.707, respectively) and abstract authors (P = 0.429, P = 0.062) was similar over the years. Of all abstracts, sex of the presenter or last abstract author were not associated with study outcomes (P = 0.718, P = 0.4331), nor with impact factor of subsequently published papers (P = 0.209, P = 0.661). Conclusions: There is a clear gender disparity in the presentation of oncological research at two main conferences, with less than a third of abstract authors female and less than a quarter of these studies presented by a woman. The lack of visibility of female researchers at presentations on these conferences could impair the acknowledgement for their research, opportunities in their academic career, and even hamper heterogeneity and outcomes in research.
Clinical and molecular characterization of patients with acute myeloid leukemia and sole trisomies of chromosomes 4, 8, 11, 13 or 21
Authors: Bhavana Bhatnagar, Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Krzysztof Mrózek, Deedra Nicolet, Dimitrios Papaioannou, Christopher J. Walker, Shelley Orwick, James S. Blachly, Jonathan E. Kolitz, Bayard L. Powell, Andrew J. Carroll, Richard M. Stone, John C. Byrd, Clara D. Bloomfield
Journal: Leukemia (2019)
A novel anticancer agent, benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride, activates multiple immunologic mechanisms of an antitumor response.
Authors: Alexei Kirkin, Karina Dzhandzhugazyan, Jens Fang, Steen Lindkair-Jensen, Per Guldberg
Journal: Journal of Clinical Oncology (2013)

e12024 Background: BP-C1 (a combination of a benzene polycarboxylic acids complex (BP-Cx-1) with cis-diamineplatinum in a very low concentration) was demonstrated to be safe and effective in the treatment of stage IV breast cancer. Methods: In order to investigate whether the immune system mediates some of the clinical activity of BP-C1, we conducted an in vitro study of the immune modulating properties of this compound. The study was done using peripheral blood mononuclear cells from healthy donors. Results: It was demonstrated that the production of a number of cytokines was significantly increased by BP-C1, first of all IL-1beta, TNF-alpha, GM-CSF, IFN-gamma, and IL-25. The carrier molecule, BP-Cx-1, alone also stimulated IL-6 production. Experiments with isolated cultures of monocytes and lymphocytes indicated that the primary targets for these reagents are monocytes. Activation of monocytes leads to two major effects: a) the production of cytokines that are able to increase the anti-tumor activity of lymphocytes, and b) the acquired ability of monocytes to inhibit tumor cell growth. In addition, direct effects on lymphocytes were also demonstrated, exemplified by the induction of IL-25 production. Conclusions: In conclusion, it was demonstrated that BP-C1 and the related compounds are able to activate multiple immunological mechanisms of anti-tumor response.
Benefit of intensified perioperative chemotherapy within high-risk CINSARC patients with resectable soft tissue sarcomas (CIRSARC).
Authors: Antoine Italiano, Jean-Yves Blay, Axel Le Cesne, Emmanuelle Bompas, Sophie Piperno-Neumann, Florence Duffaud, Francois Bertucci, Carine A. Bellera, Charles Honoré, Eberhard Stoeckle, Sylvie Bonvalot, Christine Chevreau
Journal: Journal of Clinical Oncology (2019)

TPS11078 Background: We have recently identified a gene expression signature so called “CINSARC” which is related with chromosomal instability and highly predictive of metastasis-free and overall survival in soft-tissue sarcoma (STS) patients. The prognostic relevance of this signature has been validated recently in an independent set of sarcomas from the Cancer Genome Atlas (TCGA) consortium. Despite optimal locoregional treatment, patients with high-risk CINSARC have a very poor outcome.However, the main issues with peri-operative chemotherapy in STS patients are the identification of patients who are more likely to benefit from this approach and the characterization of the best chemotherapy regimen. Indeed, in all clinical trials investigating peri-operative chemotherapy in STS, patients were included on the basis of classical histological criteria (grade, tumor size, deep location). The CINSARC is more discriminant than grade to evaluate the prognosis of STS patients (35% of grade 3 are low-risk CINSARC and 40% of grade are high-risk CINSARC). We hypothesize than: (1) 6 cycles of anthracyclines-ifosfamide is associated with improved outcome in comparison to 3 cycles of chemotherapy (ISG-STS 10-01) in patients with high-risk CINSARC STS; (2) Chemotherapy-free strategy is not associated with detrimental outcome in low-risk CINSARC STS. Methods: This is a multicenter phase III trial (sponsor: Institut Bergonié) which aims to evaluate the efficacy (intent-to-treat analysis) of 6 cycles of neoadjuvant doxorubicin + ifosfamide based chemotherapy+ surgery +/-radiotherapy (Arm B) in comparison with 3 cycles of neoadjuvant doxorubicin + ifosfamide based chemotherapy + surgery +/- radiotherapy (Arm A) in terms of 3-year progression-free survival (PFS) in high-risk CINSARC patients with resectable STS. Patients with low-risk CINSARC signature will be treated at investigator discretion. 334 patients will have to be recruited over 36 months in 10 centers of the French Sarcoma Group. This is the first study assessing the impact of peri-operative chemotherapy in STS based on a prognostic molecular signature. The study is open for accrual at time of submission. Clinical trial information: NCT03805022.
I Believe in God and in Evolution.
Journal: JAMA (1923)

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Influenza Vaccine Effectiveness Among Patients With Cancer: A Population-Based Study Using Health Administrative and Laboratory Testing Data From Ontario, Canada
Authors: Phillip S. Blanchette, Hannah Chung, Kathleen I. Pritchard, Craig C. Earle, Michael A. Campitelli, Sarah A. Buchan, Kevin L. Schwartz, Natasha S. Crowcroft, Jonathan B. Gubbay, Timothy Karnauchow, Kevin Katz, Allison J. McGeer, James D. McNally, David C. Richardson, Susan E. Richardson, Laura C. Rosella, Andrew Simor, Marek Smieja, George Zahariadis, Aaron Campigotto, Jeffrey C. Kwong
Journal: Journal of Clinical Oncology (2019)

PURPOSE Seasonal influenza vaccination is recommended for patients with cancer despite concerns of disease or treatment-associated immunosuppression. The objective of this study was to evaluate vaccine effectiveness (VE) against laboratory-confirmed influenza for patients with cancer. PATIENTS AND METHODS We conducted an observational test-negative design study of previously diagnosed patients with cancer 18 years of age and older who underwent influenza testing during the 2010-2011 to 2015-2016 influenza seasons in Ontario, Canada. We linked individual-level cancer registry, respiratory virus testing, and health administrative data to identify the study population and outcomes. Vaccination status was determined from physician and pharmacist billing claims. We used multivariable logistic regression to estimate VE, adjusting for age, sex, rurality, income quintile, cancer characteristics, chemotherapy exposure, comorbidities, previous health care use, influenza season, and calendar time. RESULTS We identified 26,463 patients with cancer who underwent influenza testing, with 4,320 test-positive cases (16%) and 11,783 (45%) vaccinated. Mean age was 70 years, 52% were male, mean time since diagnosis was 6 years, 69% had solid tumor malignancies, and 23% received active chemotherapy. VE against laboratory-confirmed influenza was 21% (95% CI, 15% to 26%), and VE against laboratory-confirmed influenza hospitalization was 20% (95% CI, 13% to 26%). For patients with solid tumor malignancies, VE was 25% (95% CI, 18% to 31%), compared with 8% (95% CI, –5% to 19%) for patients with hematologic malignancies ( P = .015). Active chemotherapy usage did not significantly affect VE, especially among patients with solid tumor cancer. CONCLUSION Our results support recommendations for influenza vaccination for patients with cancer. VE was decreased for patients with hematologic malignancies, and there was no significant difference in VE among patients with solid tumor cancer receiving active chemotherapy. Strategies to optimize influenza prevention among patients with cancer are warranted.
Recommendations for ototoxicity surveillance for childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCare Consortium
Authors: Eva Clemens, Marry M van den Heuvel-Eibrink, Renée L Mulder, Leontien C M Kremer, Melissa M Hudson, Roderick Skinner, Louis S Constine, Johnnie K Bass, Claudia E Kuehni, Thorsten Langer, Elvira C van Dalen, Edith Bardi, Nicolas-Xavier Bonne, Penelope R Brock, Beth Brooks, Bruce Carleton, Eric Caron, Kay W Chang, Karen Johnston, Kristin Knight, Paul C Nathan, Etan Orgel, Pinki K Prasad, Jan Rottenberg, Katrin Scheinemann, Andrica C H de Vries, Thomas Walwyn, Annette Weiss, Antoinette am Zehnhoff-Dinnesen, Richard J Cohn, Wendy Landier
Journal: The Lancet Oncology (2019)