tbuckley/cabot-search huggingface dataset:
Acute lower gastrointestinal bleeding during the COVID-19 pandemic – less is more!
Authors: Erik A. Holzwanger, Mohammad Bilal, Christopher G. Stallwood, Mark J. Sterling, Robert F. Yacavone
Journal: Endoscopy (2020)

The COVID-19 pandemic has presented physicians with unique challenges worldwide. In the USA, in an attempt to reduce the spread of infection, elective procedures were deferred nationwide during the pandemic [1], yet urgent and emergent procedures continued to be performed. The American Gastroenterological Association recommends that colonoscopy for lower gastrointestinal bleeding (LGIB) is considered urgent [2]. However, many factors affect this decision, including the availability of staff and personal protective equipment (PPE), and the surge of COVID-19 cases in the region. Further, active respiratory infection (such as COVID-19) increases the risk of procedures requiring sedation. A recent report demonstrated successful conservative management in six patients with upper GI bleeding (UGIB) [3]; however, to our knowledge there are no reports on COVID-19 patients with LGIB.
Onconephrology: The intersections between the kidney and cancer
Authors: Mitchell H. Rosner, Kenar D. Jhaveri, Blaithin A. McMahon, Mark A. Perazella
Journal: CA A Cancer Journal for Clinicians (2020)

Abstract Onconephrology is a new subspecialty of nephrology that recognizes the important intersections of kidney disease with cancer. This intersection takes many forms and includes drug‐induced nephrotoxicity, electrolyte disorders, paraneoplastic glomerulonephritis, and the interactions of chronic kidney disease with cancer. Data clearly demonstrate that, when patients with cancer develop acute or chronic kidney disease, outcomes are inferior, and the promise of curative therapeutic regimens is lessened. This highlights the imperative for collaborative care between oncologists and nephrologists in recognizing and treating kidney disease in patients with cancer. In response to this need, specific training programs in onconephrology as well as dedicated onconephrology clinics have appeared. This comprehensive review covers many of the critical topics in onconephrology, with a focus on acute kidney injury, chronic kidney disease, drug‐induced nephrotoxicity, kidney disease in stem cell transplantation, and electrolyte disorders in patients with cancer.
Angiotensin‐converting enzyme II expression and its implication in the association between COVID‐19 and allergic rhinitis
Authors: Hai Wang, Jia Song, Yin Yao, Yi‐Ke Deng, Zhi‐Chao Wang, Bo Liao, Jin Ma, Chao He, Li Pan, Yang Liu, Jun‐Gang Xie, Ming Zeng, Zheng Liu
Journal: Allergy (2020)

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FRI0014 Factors predicting methotrexate toxicity
Authors: M Hoekstra, A Van Ede, C Haagsma, M Van de Laar, R Laan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Methotrexate is the most effective treatment in rheumatoid arthritis. The treatment is limited by adverse events. Gastro-intestinal toxicity and hepatotoxicity occur the most. Various different factors have been reported to contribute to methotrexate toxicity. <h3>Objectives</h3> To determine predictive factors for developing methotrexate toxicity, and methotrexate withdrawal because of toxicity. <h3>Methods</h3> Data from a double-blind placebo controlled multicenter study on patients with active rheumatoid arthritis were used. In this trial the effect of folic acid (1‑2 mg/day), folinic acid (2.5 mg/week) and placebo along methotrexate therapy (7.5-maximum 25 mg/week) was compared. The patients never had methotrexate before, had active disease and a creatinine clearance &gt;50 ml/min. The three groups contained 133, 141 and 137 patients respectively. The follow-up was 48 weeks. By means of multiple stepwise regression analysis we studied the relation between baseline variables and the following: hepatotoxicity (ALAT &gt;3×ULN), the ten most frequent subjective adverse events, and methotrexate withdrawal because of toxicity. With the different toxicities we studied specific independent factors, for example NSAID's and alcohol use in hepatotoxicity. <h3>Results</h3> Hepatotoxicity: We found a significant association between folate suppletion and lack of hepatotoxicity (p &lt; 0.0001). Smoking was negatively associated with hepatotoxicity, with less hepatotoxicity when the patient smoked (p = 0.003). (P = 0.06 + 0.237 no folate – 0.023 smoking) The ten most subjective adverse events: Upper abdominal pain was significantly related to corticosteroid use (p = 0.047) (P = 0.183 + 0.109 corticosteroid) Fatigue/malaise was significantly associated with smoking (p = 0.049) (P = 0.231–0.021 smoking) Diarrhoea is significantly associated with age and a positive gasro-intestinal history, e.g. peptic ulcers and abdominal surgery (p = 0.003 and p = 0.012) (P = 0.291–0.0037age + 0.087GI-history) There were no significant associations between the other subjective adverse events (nausea, dizziness, headache, rash, stomatitis, cough and alopecia) and baseline characteristics. Methotrexate withdrawal: Significant factors predicting methotrexate withdrawal are folate suppletion, smoking and gastro-intestinal history. (p = 0.000, 0.009 and 0.019 respectively. (P = 0.124 + 0.236 no folate – 0.027 smoking + 0.103GI-history) <h3>Conclusion</h3> Folates strongly protect against hepatotoxicity and methotrexate withdrawal, but not against subjective adverse events. An interesting finding is the relation between smoking and hepatotoxicty and fatigue/malaise. In smokers the methotrexate withdrawal was significantly less. A positive gastro-intestinal history and age were predictive factors for the occurrence of diarrhoea. In this study a declining creatinine clearance was no risk factor.
Spatial and Temporal Heterogeneity of PD-L1 Expression and Tumor Mutational Burden in Gastroesophageal Adenocarcinoma at Baseline Diagnosis and after Chemotherapy
Authors: Katherine I. Zhou, Bryan Peterson, Anthony Serritella, Joseph Thomas, Natalie Reizine, Stephanie Moya, Carol Tan, Yan Wang, Daniel V.T. Catenacci
Journal: Clinical Cancer Research (2020)

Intrapatient heterogeneity of programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) in gastroesophageal adenocarcinoma (GEA) could influence their roles as predictive biomarkers for response to immune checkpoint inhibitors (ICI). In this retrospective analysis, we evaluated the spatiotemporal heterogeneity and prognostic relevance of PD-L1 expression and TMB in GEA.A cohort of 211 patients with stage II-IV GEA was retrospectively reviewed for a total of 407 tumor samples with PD-L1 expression data and 319 tumor samples with TMB data. PD-L1 status was defined as positive if combined positive score (CPS) ≥1 using the 22C3 pharmDx assay. TMB levels were categorized as low, intermediate, or high (≤5, 5-15, or >15 mutations/Mb), or using a single threshold (<10 or ≥10 mutation/Mb), determined by next-generation sequencing using a targeted gene panel.Of 407 tumors, 56% were PD-L1 negative and 44% PD-L1 positive. Of 319 tumors, 50% were TMB-low, 45% TMB-intermediate, and 5% TMB-high; 86% had <10 and 14% ≥10 mutations/Mb. TMB level was significantly associated with MSI-status. PD-L1 expression and TMB exhibited marked spatial heterogeneity between baseline primary and metastatic tumors (61% and 69% concordance), and temporal heterogeneity between tumors before and after chemotherapy (57%-63% and 73%-75% concordance). PD-L1 expression and TMB were not significantly associated with overall survival.PD-L1 expression and TMB exhibit marked spatial and temporal heterogeneity in GEA. This heterogeneity should be considered when obtaining tumor samples for molecular testing and when deciding whether ICI therapy is appropriate.See related commentary by Klempner et al., p. 6401.
C/EBPbeta contributes to patient prognosis and survival of Wilms tumor cells
Authors: Wenliang Li, Bryan Williams
Journal: Cancer Research (2004)

1162  We have previously identified a gene expression signature that predicts relapse of Wilms tumor with high accuracy. C/EBPbeta, one of the few prognostic genes in the signature, is expressed at higher levels in primary relapsing tumors and metastatic tumors than in primary non-relapsing tumors as shown by transcript profiling and immunohistochemical staining. Our observations, together with its up-regulation/hyper-activation in a number of other human cancers and its role as a critical component in a Ras-dependent transformation pathway, suggest that C/EBPbeta may play an important role in Wilms tumor progression. Using siRNA approach, we knockdowned C/EBPbeta expression in Wit49 cells, a cell line derived from a metastatic Wilms tumor, and observed a concomitant increase in spontaneous apoptosis. Caspase assay was performed to distinguish between intrinsic and extrinsic pathways of apoptosis and to assess the caspase inhibitory effect of C/EBPbeta in Wit49 cells. In addition, to determine whether the transcription regulatory function of C/EBPbeta is important for Wilms tumor cell survival, we searched for its downstream target genes. cDNA microarrays were used to examine the gene expression differences between Wit49 cells treated with C/EBPbeta and control siRNAs. Our results indicate that C/EBPbeta is not only a prognostic marker for Wilms tumor, but also a critical survival factor for Wilms tumor cells. Thus it may be a target for anti-tumor therapeutics.
Factors associated with implant survival following total hip replacement surgery: A registry study of data from the National Joint Registry of England, Wales, Northern Ireland and the Isle of Man
Authors: Jonathan Thomas Evans, Ashley William Blom, Andrew John Timperley, Paul Dieppe, Matthew James Wilson, Adrian Sayers, Michael Richard Whitehouse
Journal: PLoS Medicine (2020)

Nearly 100,000 people underwent total hip replacement (THR) in the United Kingdom in 2018, and most can expect it to last at least 25 years. However, some THRs fail and require revision surgery, which results in worse outcomes for the patient and is costly to the health service. Variation in the survival of THR implants has been observed between units and reducing this unwarranted variation is one focus of the "Getting it Right First Time" (GIRFT) program in the UK. We aimed to investigate whether the statistically improved implant survival of THRs in a high-performing unit is associated with the implants used or other factors at that unit, such as surgical skill.We analyzed a national, mandatory, prospective, cohort study (National Joint Registry for England, Wales, Northern Ireland and the Isle of Man [NJR]) of all THRs performed in England and Wales. We included the 664,761 patients with records in the NJR who have received a stemmed primary THR between 1 April 2003 and 31 December 2017 in one of 461 hospitals, with osteoarthritis as the only indication. The exposure was the unit (hospital) in which the THR was implanted. We compared survival of THRs implanted in the "exemplar" unit with THRs implanted anywhere else in the registry. The outcome was revision surgery of any part of the THR construct for any reason. Net failure was calculated using Kaplan-Meier estimates, and adjusted analyses employed flexible parametric survival analysis. The mean age of patients contributing to our analyses was 69.9 years (SD 10.1), and 61.1% were female. Crude analyses including all THRs demonstrated better implant survival at the exemplar unit with an all-cause construct failure of 1.7% (95% CI 1.3-2.3) compared with 2.9% (95% CI 2.8-3.0) in the rest of the country after 13.9 years (log-rank test P < 0.001). The same was seen in analyses adjusted for age, sex, and American Society of Anesthesiology (ASA) score (difference in restricted mean survival time 0.12 years [95% CI 0.07-0.16; P < 0.001]). Adjusted analyses restricted to the same implants as the exemplar unit show no demonstrable difference in restricted mean survival time between groups after 13.9 years (P = 0.34). A limitation is that this study is observational and conclusions regarding causality cannot be inferred. Our outcome is revision surgery, and although important, we recognize it is not the only marker of success of a THR.Our results suggest that the "better than expected" implant survival results of this exemplar center are associated with implant choice. The survival results may be replicated by adopting key treatment decisions, such as implant selection. These decisions are easier to replicate than technical skills or system factors.
Genetically raised serum bilirubin levels and lung cancer: a cohort study and Mendelian randomisation using UK Biobank
Authors: Laura Jane Horsfall, Stephen Burgess, Ian Hall, Irwin Nazareth
Journal: Thorax (2020)

Background Moderately raised serum bilirubin levels are associated with lower rates of lung cancer, particularly among smokers. It is not known whether these relationships reflect antioxidant properties or residual confounding. Objective This study aimed to investigate potential causal relationships between serum total bilirubin and lung cancer incidence using one-sample Mendelian randomisation (MR) and UK Biobank. Methods We instrumented serum total bilirubin level using two variants (rs887829 and rs4149056) that together explain ~40% of population-level variability and are linked to mild hereditary hyperbilirubinaemia. Lung cancer events occurring after recruitment were identified from national cancer registries. Observational and genetically instrumented incidence rate ratios (IRRs) and rate differences per 10 000 person-years (PYs) by smoking status were estimated. Results We included 377 294 participants (median bilirubin 8.1 μmol/L (IQR 6.4–10.4)) and 2002 lung cancer events in the MR analysis. Each 5 μmol/L increase in observed bilirubin levels was associated with 1.2/10 000 PY decrease (95% CI 0.7 to 1.8) in lung cancer incidence. The corresponding MR estimate was a decrease of 0.8/10 000 PY (95% CI 0.1 to 1.4). The strongest associations were in current smokers where a 5 μmol/L increase in observed bilirubin levels was associated with a decrease in lung cancer incidence of 10.2/10 000 PY (95% CI 5.5 to 15.0) and an MR estimate of 6.4/10 000 PY (95% CI 1.4 to 11.5). For heavy smokers (≥20/day), the MR estimate was an incidence decrease of 23.1/10 000 PY (95% CI 7.3 to 38.9). There was no association in never smokers and no mediation by respiratory function. Conclusion Genetically raised serum bilirubin, common across human populations, may protect people exposed to high levels of smoke oxidants against lung cancers.
Anti-inflammatory action of colchicine in hospitalised patients with COVID-19. Response to: ‘Colchicine treatment in community healthcare setting to prevent severe COVID-19’ by Della-Torre<i>et al</i>
Authors: Silvia Piantoni, Enrico Colombo, Roberto Furloni, Laura Andreoli, Antonio Brucato, Massimo Imazio, Paolo Airó, Mirko Scarsi
Journal: Annals of the Rheumatic Diseases (2020)

Table 1 Comparison of clinical and laboratory features at baseline and after 6 days of therapy in patients treated with standard-of-care (SoC) or colchicine plus (+) SoC Features SoC Colchicine + SoC Day 0 Day 6 P value* Day 0 Day 6 P value* C-reactive protein (mg/L) 112 (83) 114 (100) 0.
A randomized phase II study of a combination of docetaxel and S-1 versus docetaxel monotherapy in pts with NSCLC previously treated with platinum-based chemotherapy: Results of Okayama Lung Cancer Study Group (OLCSG) trial 0503
Authors: Y. Segawa, K. Hotta, N. Takigawa, K. Matsuo, H. Yoshioka, H. Hayashi, N. Nogami, M. Tabata, K. Kiura, M. Tanimoto
Journal: Journal of Clinical Oncology (2009)

8058 Background: Recent studies have demonstrated that docetaxel (DOC) monotherapy provides a significant survival prolongation in relapsed pts with NSCLC. However, its benefit remains modest and further improvement is needed. S-1 is a newly developed oral 5-fluorouracil derivative, possessing a promising anti-tumor activity in NSCLC. Based on a superior effect of combination of DOC and 5-fluorouracil derivative (capecitabine) to DOC alone in anthracycline-pretreated breast cancer pts, we conducted a randomized phase II study to evaluate the clinical significance of adding S-1 to DOC in the second-line setting. Methods: Pts with relapsed NSCLC to the first-line platinum-based chemotherapy were randomly allocated to DOC monotherapy (A arm; 60 mg/m 2 , day 1, q 3 wks) or a combination chemotherapy (B arm) of DOC (40 mg/m 2 , day 1, q 3 wks) and S-1 (80 mg/m 2 , days 1 to 15). The doses of arm B were determined based on the results of a phase I study conducted for Japanese pts with gastric cancer (Anticancer Res 24: 1843, 2004). The primary endpoint was response rate and secondary endpoints included OS, PFS and toxicity. Results: Between 2005 and 2008, 60 pts were enrolled (A/B: 29/31 pts). Demographics of the pts were as follows: M/F: 49/11, Ad/others: 40/20, ECOG-PS 0/1: 38/22. A median number of courses administered was 4 (range: 1 to 6). Objective response was obtained in 6 (20.7%) and 5 pts (16.1%) in arms A and B, respectively. With a median follow-up time of 16.9 months, MST and median PFST in arm A were longer than arm B (22.9 vs. 8.7 months and 3.7 vs. 3.4 months, respectively). The major toxicity was myelosuppression, with grade 4 neutropenia of 62% vs. 29%, whereas thrombocytopenia was generally mild. Grade 3 febrile neutropenia was observed in 4 and 1 pts, none of whom further developed grade 5 toxicity. Other grade 3 or greater non-hematological adverse events included fever (B: 1 pt), pneumonitis (B: 1 pt), liver dysfunction (B: 2 pts), skin rash (B: 1 pt), and all of them were improved with an appropriate supportive care. Conclusions: The trial suggests that docetaxel monotherapy remains a standard therapy for NSCLC pts who relapsed to platinum-based chemotherapy. No significant financial relationships to disclose.
Phase II study of combination therapy with docetaxel, cisplatin, and S-1 (DCS) for advanced gastric cancer: (KDOG 0601)
Authors: N. Nakayama, W. Koizumi, T. Sasaki, S. Tanabe, K. Nishimura, K. Higuchi, S. Takagi, C. Katada, M. Azuma, K. Saigenji
Journal: Journal of Clinical Oncology (2009)

4555 Background: Our previous phase I study (Oncology 2008, 75:1–7) provided evidence that combination chemotherapy with docetaxel, cisplatin, and S-1 (DCS) is effective and well tolerated in patients with advanced gastric cancer. The present multicenter phase II study was conducted to confirm the efficacy and toxicity of DCS in advanced gastric cancer. Methods: Eligibility criteria included a histologically proved diagnosis of gastric adenocarcinoma with at least one measurable metastatic lesion, no previous treatment for gastric cancer except for surgery, an ECOG performance status of 0 to 2, and adequate organ function. Docetaxel (40 mg/m 2 ) and cisplatin (70–60 mg/m 2 ) were given intravenously on day 1, and S-1 was given orally at a dose of 40 mg/m 2 twice daily from days 1 to day 14 of a 28-day cycle. Patients received a maximum of 6 cycles. Subsequently, patients were given repeated cycles of S-1 plus docetaxel (DS). The primary endpoint was the objective response rate. Results: 59 patients (47 men, 12 women) were enrolled. The median age was 62 (range: 35–75) years. PS 0/1/2 was 40/18/1. The median number of treatment cycles was 7 (DCS 6+DS 1: range, 1–20). Because myeloid suppression and renal dysfunction developed during the study, we lowered the recommended dose of cisplatin from 70 mg/m 2 to 60 mg/m 2 . The dose of cisplatin was 70 mg/m 2 in 19 patients and 60 mg/m 2 in 40. The overall response rate was 81.3% (48/59; 95% CI, 80.7–91.2). The response rates with cisplatin 70 mg/m 2 and 60 mg/m 2 were 78.9% (95% CI, 60.5–97.2) and 82.5% (95% CI, 70.7–94.2), respectively. Tumor down-staging was achieved in 9 (18.7%) of the 48 patients who responded to treatment. The median survival time and median progression-free survival were not reached. Grade 3 or 4 major toxicity comprised leukopenia (44.0%), neutropenia (72.8%), anemia (15.2%), febrile neutropenia (13.5%), anorexia (6.7%), nausea (5.1%), vomiting (5.1%), fatigue (1.6%), and diarrhea (5.1%). There was one treatment-related death caused by the perforation of the primary tumor. This patient refused surgery. Conclusions: DCS was a well-tolerated regimen with a high response rate in patients with advanced gastric cancer. Cisplatin at a dose of 60 mg/m 2 was considered adequately effective. No significant financial relationships to disclose.
Comment on ‘Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19’ by Konig<i>et al</i>. Long-term exposure to hydroxychloroquine or chloroquine and the risk of hospitalisation with COVID-19: a nationwide, observational cohort study in 54 873 exposed individuals and 155 689 matched unexposed individuals in France
Authors: Emilie Sbidian, Laetitia Penso, Philippe Herlemont, Jérémie Botton, Bérangère Baricault, Laura Semenzato, Jérome Drouin, Alain Weill, Rosemay Dray-Spira, Mahmoud Zureik
Journal: Annals of the Rheumatic Diseases (2020)

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Targeting the Otub1/c-Maf axis for the treatment of multiple myeloma
Authors: Yujia Xu, Min Xu, Jiefei Tong, Xiaowen Tang, Jinhao Chen, Xuehan Chen, Zubin Zhang, Biyin Cao, A. Keith Stewart, Michael F. Moran, Depei Wu, Xinliang Mao
Journal: Blood (2020)
Willingness of breast cancer survivors to participate in a randomized controlled trial (RCT) of digital mammography with or without magnetic resonance imaging (MRI) as breast cancer (BC) surveillance: A feasiblity study
Authors: E. Warner, D. Tsoi, L. Bordeleau, C. Brezden, C. Holloway
Journal: Journal of Clinical Oncology (2009)

1534 Background: Although no RCT of MRI screening has ever been performed, and thus its impact on survival is unknown, MRI (plus mammography) has become the standard of care for screening women at very high risk for BC due to its superior sensitivity. The current ASCO guideline for surveillance of women with a past history of BC patients for ipsilateral recurrence or contralateral BC is annual mammography; however, MRI is often being ordered as well. A RCT for this population is still theoretically feasible assuming one could recruit a sufficient number of patients. We conducted a study to evaluate the willingness of BC survivors to participate in a RCT of digital mammography with or without MRI. Methods: In this multi-center, cross-sectional cohort survey, consecutive women ages 20 to 59 with invasive BC who had completed all primary therapy (except hormonal therapy), had at least one remaining breast and no evidence of metastatic disease, were consented in clinic to complete a self-administered questionnaire. Results: 348 women at four study sites across Toronto, Canada, were enrolled over 10 months. Median age 51 years, 76% Caucasian, 69% had BC within the last 5 years, 37% had previous mastectomy. At diagnosis, 71% BC had been visible on mammogram; 45% had undergone diagnostic MRI. 22% continued to have MRI as part of surveillance imaging, especially women younger than 40 years. 58% agreed to consider participating in the proposed RCT, and 16% remained neutral. Women who had undergone mastectomy were more likely to consider the trial (71% vs. 52%). The most common reason for not considering the trial was that they were already getting surveillance MRI. Other reasons were additional false positive tests and biopsies (34%), discomfort associated with MRI (28%), and fear that their anxiety about cancer recurrence would increase (16%). Conclusions: A RCT of MRI surveillance for BC survivors younger than age 60 is still feasible at centers where annual MRI is not yet routinely recommended for this population. No significant financial relationships to disclose.