tbuckley/cabot-search huggingface dataset:
Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study
Authors: Thaís Armangue, Gemma Olivé-Cirera, Eugenia Martínez-Hernandez, Maria Sepulveda, Raquel Ruiz-Garcia, Marta Muñoz-Batista, Helena Ariño, Veronica González-Álvarez, Ana Felipe-Rucián, Maria Jesús Martínez-González, Veronica Cantarín-Extremera, Maria Concepción Miranda-Herrero, Lorena Monge-Galindo, Miguel Tomás-Vila, Elena Miravet, Ignacio Málaga, Georgina Arrambide, Cristina Auger, Mar Tintoré, Xavier Montalban, Adeline Vanderver, Francesc Graus, Albert Saiz, Josep Dalmau, Alberto Alcantud, Sergio Aguilera-Albesa, Diana Alvarez Demanuel, Mireia Alvarez Molinero, Lourdes Aquino Fariña, Luisa Arrabal, Gema Arriola-Pereda, Gemma Aznar-Laín, Maite Benavides-Medina, Teresa Bermejo, Raquel Blanco-Lago, Eva Caballero, Rocío Calvo, Ana Camacho Salas, David Conejo-Moreno, Verónica Delgadillo-Chilavert, Amagoia Elosegi-Castellanos, Vanesa Esteban Canto, Joaquín Fernández-Ramos, Montserrat Garcia-Puig, Ainhoa García-Ribes, Hilario Gómez-Martín, Desire Gonzalez-Barrios, Luis González-Gutiérrez-Solana, Sara Jimena-Garcia, María Jiménez-Legido, Natalia Juliá-Palacios, Eduardo López-Laso, Itxaso Martí-Carrera, Marta Martínez González, Lucía Martín-Viota, Simone Mattozi, Elena Maqueda-Castellote, Maria D M Mendibe, Maria D Mora-Ramírez, Beatriz Muñoz-Cabello, Juan Navarro-Morón, Tania Nunes-Cabrera, Gabriela Orellana, Berta Pujol-Soler, Luis Querol, Alfredo Ramírez, Maria I Rodriguez-Lucenilla, Cesar Ruiz, Víctor Soto-Insuga, Laura Toledo Bravo de Laguna, Eulàlia Turon-Viñas, Maria Vázquez-López, Cristina Villar-Vera
Journal: The Lancet Neurology (2020)
Gene mutations distinguishing gastric from colorectal and esophageal adenocarcinomas.
Authors: Tuyen Hoang, Darryl Hiyama, Farshid Dayyani
Journal: Journal of Clinical Oncology (2020)

424 Background: Genetic analysis of gastrointestinal malignancies shows a great number of mutations. Most mutations found in gastric tumors are found in colorectal and esophageal tumors, and vice versa. The challenge remains to identify mutations that distinguish gastric from colorectal and esophageal cancers. Using open-access cancer genomics data, we sought to identify mutations that accounted for the unique phenotypic features of gastric tumors. Methods: Thirteen cancer genomics datasets with demographic, clinical, and genetic variables were analyzed. Each subject was flagged with or without a mutated gene. For each anatomical location, pathologic stage and histology were compared between subjects with and without a specific mutated gene, using two-sample t tests, adjusted for multiple gene testing. Results: Analysis included 1,915 subjects with valid pathologic stage and histology. Mean age was 68 years (SD=10). About 54% were female. The most common race was Caucasian (37%) while minorities were rare with high rate of missing data (44%). Pathologic stage: 20% stage I, 35% stage II, 31% stage III, and 14% stage IV. Anatomical location: 29.5% gastric, 59.5% colorectal, and 11.0% esophageal. Histology of gastric cancer: 61.4% intestinal, 23.2% diffuse, 14.9% others, and 0.5% missing. One gene–HEATR7B2–though rarely mutated, occurred only in stage IV of gastric tumors. Two mutated genes–CDH1, RHOA–distinguished diffuse from intestinal gastric histology. One mutated gene–CDH1–distinguished gastric from colorectal and esophageal tumors. Conclusions: This study confirmed the genes involved in the pathogenesis of gastric malignancies (CDH1, RHOA) and linked one novel gene to stage IV of gastric tumors (HEATR7B2). Future animal and human epidemiologic studies are needed to elucidate how this novel gene contributes to gastric malignancies.
上腕内皮血管運動機能および頸動脈プラークecholucencyの合同の超音波評価による、メタボリックシンドロームにおける心血管イベント予測に対する相加値 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Nakamura T, Kitta Y, Iwaoka M, Takano H, Kodama Y, Kawabata K, Obata Je, Mende A, Abe M, Kugiyama K
Journal: Circulation (2006)
The antidiarrheal efficacy of a proprietary amino acid mixture (enterade) in neuroendocrine tumor (NET) patients: Updated data.
Authors: Aman Chauhan, Rachel C. Miller, Laura Luque, Heidi Weiss, Lowell Brian Anthony
Journal: Journal of Clinical Oncology (2020)

614 Background: Diarrhea is a common quality of life limiting symptom seen in neuroendocrine tumor patient. Diarrhea in these patients could be due to excessive serotonin production, secondary to post-operative short gut syndrome, steatorrhea from somatostatin analogs, bile acid colitis or intestinal bacterial overgrowth. In this study we summarize our single center experience with enterade. Methods: Medical records of all the NET patients treated with enterade for symptomatic diarrhea were retrospectively reviewed after appropriate IRB approval. Patients were treated at Markey cancer center between May 2017-June 2019. Results: Total 98 patients were offered enterade. enterade was instructed to be taken as one 8 Oz bottle BID for 1 week. Antidiarrheal efficacy data was available on 49 patients at the time of abstract submission. 37 (75%) patients had GEPNETs, 8 had bronchial NETs, 1 gynecological NET and 3 patients had unknown primary. 28 (57%) patients had history of prior bowel resection either for primary neuroendocrine tumor resection or debulking. 28 (57%) patients were on somatostatin analog at the time of initiation of enterade. 42 (85%) out of 49 patients reported subjective improvement in diarrheal symptoms. 27 (64%) out of these 42 responders reported at least 50 percent reduction in diarrhea frequency. Conclusions: 85% (42/49) neuroendocrine tumor patients reported improvement in diarrhea with enterade. 64% (27/42) reported more than 50% reduction in diarrhea frequency. A prospective Phase II study of enterade in neuroendocrine tumor patients with quality of life limiting diarrhea is currently being conducted (NCT03722511).
Random vs Targeted Urine Drug Testing Among Patients Undergoing Long-term Opioid Treatment for Cancer Pain
Authors: Joseph Arthur, Zhanni Lu, Kristy Nguyen, David Hui, Bernard Prado, Tonya Edwards, Eduardo Bruera
Journal: JAMA Oncology (2020)

Random vs Targeted Urine Drug Testing Among Patients Undergoing Long-term Opioid Treatment for Cancer PainThere is limited information on best practices regarding urine drug testing (UDT) during long-term opioid therapy for cancer pain. 1 Practices involve random UDT 1 or UDT based on risk for nonmedical opioid use. 2 The main objective of this study was to report the frequency of abnormal UDT findings among patients who underwent random vs targeted testing.Methods | Between April 1, 2017, and January 31, 2018, electronic medical records of consecutive patients attending an outpatient supportive care clinic who underwent random UDT were reviewed.Eligible patients were 18 years or older, had a diagnosis of cancer, and were receiving opioid therapy.The results were compared with a cohort of consecutive patients who underwent targeted UDT wherein the test was ordered based on clinical suspicion of nonmedical opioid use.The institutional
Interstitial Lung Disease in Relatives of Patients with Pulmonary Fibrosis
Authors: Gary M. Hunninghake, Luisa D. Quesada-Arias, Nikkola E. Carmichael, Jose M. Martinez Manzano, Sergio Poli De Frías, Maura Alvarez Baumgartner, Lisa DiGianni, Shannon N. Gampala-Sagar, Dominick A. Leone, Swati Gulati, Souheil El-Chemaly, Hilary J. Goldberg, Rachel K. Putman, Hiroto Hatabu, Benjamin A. Raby, Ivan O. Rosas
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Although relatives of patients with familial pulmonary fibrosis (FPF) are at an increased risk for interstitial lung disease (ILD), the risk among relatives of sporadic idiopathic pulmonary fibrosis (IPF) is not known.Objectives: To identify the prevalence of interstitial lung abnormalities (ILA) and ILD among relatives of patients with FPF and sporadic IPF.Methods: Undiagnosed first-degree relatives of patients with pulmonary fibrosis (PF) consented to participate in a screening study that included the completion of questionnaires, pulmonary function testing, chest computed tomography, a blood sample collection for immunophenotyping, telomere length assessments, and genetic testing.Measurements and Main Results: Of the 105 relatives in the study, 33 (31%) had ILA, whereas 72 (69%) were either indeterminate or had no ILA. Of the 33 relatives with ILA, 19 (58%) had further evidence for ILD (defined by the combination of imaging findings and pulmonary function testing decrements). There was no evidence in multivariable analyses that the prevalence of either ILA or ILD differed between the 46 relatives with FPF and the 59 relatives with sporadic IPF. Relatives with decrements in either total lung or diffusion capacity had a greater than 9-fold increase in their odds of having ILA (odds ratio, 9.6; 95% confidence interval, 3.1-29.8; P < 0.001).Conclusions: An undiagnosed form of ILD may be present in greater than 1 in 6 older first-degree relatives of patients with PF. First-degree relatives of patients with both familial and sporadic IPF appear to be at similar risk. Our findings suggest that screening for PF in relatives might be warranted.
Association of a Type 2–Polarized T Cell Phenotype With Methotrexate Nonresponse in Patients With Rheumatoid Arthritis
Authors: Drew Slauenwhite, Sarah M. McAlpine, John G. Hanly, Anikó Malik, Ian D. Haidl, Jean S. Marshall, Thomas B. Issekutz
Journal: Arthritis & Rheumatology (2020)

Rheumatoid arthritis (RA) is a chronic inflammatory disease mediated through complex immunologic pathways. Among RA patients receiving low-dose methotrexate (MTX) monotherapy, approximately one-half exhibit a meaningful clinical response within the first 6 months of starting treatment. Whether baseline immune phenotypes differ between subsequent MTX responders and nonresponders is unknown. This study utilized comprehensive T cell immunophenotyping to identify specific immunologic pathways associated with MTX-nonresponsive joint inflammation in patients with RA.In total, 32 patients with recent-onset RA were treated with MTX therapy. After 6 months, 15 patients were categorized as responders and 17 as nonresponders. Comprehensive blood T cell immunophenotyping, using multiparameter immunofluorescence flow cytometry analyses, was performed at baseline and following 6 months of treatment.Baseline measures of disease activity (Disease Activity Score in 28 joints [DAS28], C-reactive protein level, and erythrocyte sedimentation rate) did not differ between MTX responders and nonresponders following MTX treatment. Frequencies of CD4+ and CD8+ T cells were skewed to favor higher CD4:CD8 T cell ratios in MTX responders compared to nonresponders (P < 0.05). The proportion of inducible costimulator-expressing Treg cells was significantly greater among MTX nonresponders. Interleukin-13 (IL-13)-producing, but not interferon-γ- or IL-17-producing, CD4+ effector memory T (Tem) cells were significantly more frequent in MTX nonresponders (P < 0.05). The ratio of IL-13+:IL-17+ Tem cells among CD4+ Tem cells was 1.9-fold higher in MTX nonresponders compared to responders (P < 0.05). Both the CD4:CD8 T cell ratio and the frequency of IL-13+CD4+ Tem cells correlated with changes in the DAS28 score following MTX treatment, whereas T cell expression of immune checkpoint inhibitor markers (CTLA-4, programmed death 1, and T cell immunoglobulin and mucin domain-containing protein 3) did not differ between MTX responders and nonresponders.We observed a bias toward type 2-polarized T cell inflammatory responses in the peripheral blood of MTX-nonresponsive RA patients. Targeting the IL-13+CD4+ T cell pathway could be a new therapeutic strategy in RA patients whose disease remains resistant to MTX.
Survival and quality of life after isolated upper abdominal perfusion with chemofiltration (UAP-F) for stage III and IV pancreatic cancer.
Authors: Karl R Aigner, Sabine Gailhofer, Emir Selak, Kornelia Aigner
Journal: Journal of Clinical Oncology (2020)

681 Background: In order to increase response and survival rates of advanced pancreatic cancer at good quality of life, UAP-F was clinically tested. We report on feasibility, safety, overall survival and quality of life of 79 patients in stage III and 142 patients in stage IV submitted to UAP with subsequent chemofiltration for lowering of systemic drug exposure. Methods: This technique is achieved with stop-flow balloon catheters introduced via the femoral artery and vein. The arterial balloon is placed below the celiac axis and proceeded beneath the diaphragm after injection of a three-drug combination consisting of cisplatin (CDDP), adriamycin (ADM) and mitomycin (MMC). Because of tenfold increased cytotoxicity of ADM and MMC, the perfusion is performed under hypoxic condition. Perfusion time is 15 minutes followed by 30 – 45 minutes of chemofiltration. Results: Median survival was 12.1 months and 8.7 months in stage III and IV respectively. One-year survival was 49.4 % and 37 % for stage III and IV, and 3-years survival 21.7 % and 7.7 % for stage III and IV respectively. Cisplatin levels in the arterial circuit amounted to 60.000 ng/ml and 6.000 ng/ml in the venous line. Resolution of ascites was achieved within two therapies in 33/36 cases with UAP-F. Toxicity was generally mild, not exceeding WHO grade II and amounted to grade III or IV only in patients after prior severe systemic chemotherapy. Conclusions: Upper abdominal perfusion with chemofiltration is a safe technique for advanced cancers of the pancreas, increasing survival time and maintaining quality of life.
Quality of timely adjuvant chemotherapy for veterans with colorectal cancer.
Authors: Richard Lewis Martin, Gretchen C. Edwards, Lauren R. Samuels, Christianne L. Roumie
Journal: Journal of Clinical Oncology (2020)

78 Background: National Comprehensive Cancer Network (NCCN) recommends adjuvant chemotherapy for patients with high risk stage II or stage III colorectal cancer (CRC). Treatment within 8 weeks of surgery improves disease free survival and decreases recurrence. National Veterans Health Administration (VHA) CRC data demonstrated adherence to this standard; however, there was regional variation. We sought to describe time to treatment at a Southeast Regional VHA facility to determine local targets for quality improvement initiatives. Methods: We retrospectively reviewed 705 electronic medical records of patients who underwent colorectal surgery from January 1, 2000 to December 31, 2015 at VHA Tennessee Valley Healthcare System. Two trained clinician abstractors reviewed standard elements (k = 0.79 – 0.92). The population included patients with pathological stage high risk II or III CRC and excluded those with metastatic disease or documented NCCN defined exclusion from chemotherapy. We analyzed 2 populations; chemotherapy received and a sensitivity analysis population of patients who were eligible for, but did not receive, chemotherapy (no documentation of NCCN ineligibility or declined). The primary outcome was chemotherapy within 8 weeks of surgery, evaluated during three time periods due to changes in NCCN guidelines. Results: Of 705 colorectal surgeries, we excluded 262 for non-cancers, 220 for stage I or low-risk stage II cancers, and 46 for NCCN defined exclusion, yielding 177 cases: 120 colon and 57 rectal cancers. Patients were 98% male, 85% white, and median age 64 years [Interquartile Range 60, 70]. Among those receiving chemotherapy (123/177 [69.5%]), median time to treatment was 50.5 days [40,64]; with 63% receiving chemotherapy within 8 weeks. Results varied over time. Between 2000-2004 75% received within 8 weeks; 2005-2009, 62%; 2010-2015, 41%. Including all eligible patients, the proportion receiving timely treatment declined; overall 44%; 2000-2004, 57%; 2005-2009, 45%; 2010-2015, 25%. Conclusions: Improving care processes for patients with CRC can improve timely treatment. Exploring barriers such as prolonged hospitalization, wound healing, and port placement may reveal areas for quality improvement.
Potency of CD8+ T-cell mediated antitumor immunity from intratumoral immunotherapy with STING agonist, ADU-S100, in an esophageal adenocarcinoma model.
Authors: Laila Babar, Ali Hussainy Zaidi, Ronan Joseph Kelly, Ashten N. Omstead, Ping Zheng, Juliann E. Kosovec, Shahin Ayazi, Gene Grant Finley, Blair Anderson Jobe, Ajay Goel, Anastasia Gorbunova, Madison Salvitti
Journal: Journal of Clinical Oncology (2020)

408 Background: Esophageal adenocarcinoma (EAC) is a deadly disease with poor prognosis due to limited treatment options. STING is a transmembrane protein that activates the transcription of type I IFN genes, resulting in the stimulation of APCs and enhanced CD8+ T-cell infiltration. Recently, STING agonists have demonstrated durable anticancer activity in solid tumors when used alone and in combination with either chemotherapy, radiation or immunotherapy. In this study we evaluated the efficacy and immunomodulatory effects of STING agonist +/- radiation in an established EAC model. Methods: Esophagojejunostomy was performed on rats to induce reflux leading to the development EAC. At 32 weeks post operatively, rats received either STING (ADU-S100) or placebo (PBS), +/- 16Gy radiation. Drug efficacy was evaluated by pre- and post- treatment MRI, serial biopsies, histology and RT-PCR. Additionally, immunofluorescence was performed using CD8 and PD-L1 antibodies. Results: A comparison of MRIs in the study groups between 32 and 40 weeks demonstrated a mean increase in percentage tumor volume of 76.7 % and 152.4% in the P and P+R arms and a decrease of 30.1 % and 50.8% in the S and S+R arms, respectively (ANOVA test p &lt; 0.0001) Overall, the S+R group demonstrated the best results with maximum mean volume reduction with all cases responding. Downstream gene expression, pre, on, and post- treatment demonstrated significant upregulation of IFNβ, TNFα, IL-6 and CCL-2 in the treatment groups compared with placebo. On and post treatment, radiation alone, ADU-S100 alone and ADU-S100 + radiation groups demonstrated enhanced PD-LI expression, induced by higher densities of IFNγ producing CD8+ T-cells (p &lt; 0.01). Conclusions: ADU-S100 +/- radiation exhibits potent anti-tumor efficacy and a promising immunomodulatory profile in a de novo EAC model providing the rationale for clinical testing, likely concurrently in combination with immune checkpoint inhibitors.
Systemic inflammation, adjuvant chemotherapy, and survival in stage III colorectal cancer: Results from the ScotScan Colorectal Cancer Collaborative.
Authors: James Hugh Park, Anniken Jorlo Fuglestad, Anne Helene Kostner, Agata Oliwa, Campbell SD Roxburgh, Paul G. Horgan, Janet Shirley Graham, Christian Kersten, Donald C. McMillan
Journal: Journal of Clinical Oncology (2020)

228 Background: The systemic inflammatory response (SIR) is a poor prognostic marker in patients with colorectal cancer (CRC), and predicts poor outcome following adjuvant chemotherapy. Whether this may be influenced by chemotherapy regime is not known. The present study examined the relationship between the pre-operative SIR, adjuvant therapy regime, and survival of patients with stage III CRC in the ScotScan cohort. Methods: Patients with stage III CRC in Scotland (1997-2015, n= 317) and Norway (2000-17, n= 312) were included. The pre-operative SIR was measured using C-reactive protein (CRP≤10mg/L or &gt; 10mg/L). Adjuvant status was categorised as none, 5-fluorouracil-only (5FU or capecitabine), or oxaliplatin-combination (Ox). Relationship with 3 year overall (OS) and cancer-specific survival (CSS) was examined. Results: Rates of Ox were comparable between cohorts (Scotland – 26% vs. Norway 28%), although more patients from Norway received single 5FU (4% vs. 19%, P= 0.005). 36% of each cohort were systemically inflamed. Ox was associated with superior OS (90%) and CSS (92%) when compared to 5FU (77% and 84%) and no therapy (61% and 72%, both P&lt; 0.001). Stratified by SIR, patients with CRP≤10mg/L receiving Ox or 5FU had comparable 3yr OS greater than those receiving none (90% vs. 88% vs. 67%), whereas those with CRP &gt; 10mg/L receiving Ox had superior survival than those receiving 5FU or no therapy (89% vs. 64% vs. 53%, P-for interaction = 0.101). Results were similar for CSS (CRP≤10mg/L: 91% vs. 94% vs. 79%; CRP &gt; 10mg/L: 94% vs. 72% vs. 62%, P-for interaction= 0.01). Although patients receiving Ox were younger and less comorbid, both use of Ox and SIR remained independently associated with OS and CSS. Conclusions: Although selection bias in the choice of adjuvant therapy may confound analysis, this study suggests the SIR may aid in determining response to adjuvant therapy. Whereas non-inflamed patients with stage III CRC may benefit from single 5FU, those with an elevated SIR may benefit greater from more intensive, Ox-based regimes. These results remain to be validated, however support the use of the SIR as a prognostic and predictive biomarker in patients with stage III CRC.
Local and Systemic Immune Dysregulation Alters Glioma Growth in Hyperglycemic Mice
Authors: Ian Y. Zhang, Hui Zhou, Huili Liu, Leying Zhang, Hang Gao, Shunan Liu, Yanyan Song, Darya Alizadeh, Hongwei Holly Yin, Raju Pillai, Behnam Badie
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Unlike most cancers, no clear epidemiological correlation between diabetes (Db) and malignant glioma progression exists. Because hyperglycemia activates proinflammatory pathways through the receptor for advanced glycation endproducts (RAGE), we hypothesized that Db can also promote malignant glioma progression. Experimental Design: We compared the growth of two phenotypically diverse syngeneic glioma models in control and diabetic mice. Tumor growth and antitumor immune responses were evaluated in orthotopic and heterotopic models and correlated to RAGE and RAGE ligand expression. Results: Irrespective of tumor implantation site, growth of a “classical” glioma model, GL261, increased in hyperglycemic mice and was mediated by upregulation of RAGE and its ligand, HMGB1. However, growth of a “mesenchymal” glioma subtype, K-Luc, depended on tumor implantation site. Whereas heterotopic K-Luc tumors progressed rapidly in Db mice, intracranial K-Luc tumors grew slower. We further showed that hyperglycemia inhibited the innate antitumor inflammatory responses in both models. Although this contributed to the accelerated growth of heterotopic tumors, suppression of tumor inflammatory responses dampened the growth of orthotopic K-Luc gliomas. Conclusions: Hyperglycemia may enhance glioma growth through promotion of RAGE expression and suppression of antitumor immune responses. However, abrogation of the proinflammatory milieu in tumors may also dampen the growth of inflammatory glioma subtypes in the brains of diabetic mice. This dichotomy in glioma growth response to hyperglycemia may partly explain why conflicting epidemiological studies show both an increased risk and a protective effect of Db in patients with malignant gliomas.