tbuckley/cabot-search huggingface dataset:
Continued improvement in survival in multiple myeloma (MM) including high-risk patients.
Authors: Bharat Nandakumar, Moritz Binder, Angela Dispenzieri, Prashant Kapoor, Francis Buadi, Morie A. Gertz, Martha Lacy, David Dingli, Lisa Hwa, Nelson Leung, Suzanne R. Hayman, Wilson I. Gonsalves, Taxiarchis Kourelis, Eli Muchtar, Rahma M. Warsame, Ronald S. Go, Miriam A. Hobbs, Robert A. Kyle, S. Vincent Rajkumar, Shaji Kumar
Journal: Journal of Clinical Oncology (2019)

8039 Background: Treatment of MM has evolved significantly over the past decade, with increasing use of multi-drug combinations for initial therapy. In addition, supportive care approaches have also improved. We examined how these improvements have translated to survival outcomes in patients with newly diagnosed MM. Methods: Patients (n=3449) with a diagnosis of MM made between 2004 and 2017 and seen at Mayo Clinic within six months of the diagnosis, were included in this analysis. Patients were divided into three groups based on the year of diagnosis; group 1- 2004-07 (n=831), group 2-2008-12 (n=1161), and group 3-2013-17 (n=1457). Survival of the groups were estimated using Kaplan-Meier method, and compared using log rank test. Results: The median age was 64 years (22 to 96); 60% were male and 40% were female. 14% were &gt;75 years, 33% were aged 65-75 and 53% were &lt;65 years. The median overall survival for the whole cohort was 5.7 years (95%CI; 5.4, 6.3). The median OS for the groups 1, 2 and 3 were 3.9, 6.3 and NR, respectively; p&lt;0.001. The 4-year survival estimates were 50%, 62%, and 75%, respectively. We then explored the improvements in patient subgroups. While all patients experienced improvements in OS over time, improvement in group 3 was most prominent for those &gt;75 years. In patients &lt;65 years, the 4-yr OS for groups 1, 2 and 3 were 57, 71, and 79% respectively. In patients 65-75 years of age, the 4-yr OS for groups 1, 2 and 3 were 48, 60, and 75% respectively. In patients &gt;75 years, the 4-yr OS for groups 1, 2 and 3 were 24, 35, and 56% respectively. While patients with high-risk disease did not see as much benefit in the earlier period, substantial progress was seen in the last group. The 3-yr OS for patients with high-risk cytogenetics were 52, 55, and 73% for groups 1, 2 and 3 compared to 67, 75, and 85% for standard-risk cytogenetics respectively. 2067 patients were staged according to the International Staging System and the median OS for stages 1, 2 and 3 were 6.5, 4.6 and 2.4 in group 1; 9.2, 6.6 and 3.5 in group 2 and NR for any of the stages in group 3. Conclusions: The results confirm continued improvement in survival of newly diagnosed multiple myeloma patients, including elderly and high-risk MM.
Isolation and characterization of exosomes from IDH mutant gliomas.
Authors: Nils Ludwig, Aparna Rao, Saigopalakrishna Saileelaprasad Yerneni, Nduka Amankulor, Theresa Whiteside
Journal: Journal of Clinical Oncology (2019)

152 Background: Mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) are found in &gt; 70% of intermediate grade gliomas. Gain-of-function mutations in IDH1 promote diffuse glioma formation through epigenetic reprogramming of a number of genes, including immune-related genes. Tumor-derived exosomes (TEX) accumulate in the tumor microenvironment (TME) and in body fluids of patients. TEX serve as a communication system between tumor and normal cells. Circulating TEX carry a complex molecular and genetic cargo and interfere with functions of immune cells. This study characterizes TEX produced by IDH mutant glioma spheres and TEX from plasma of patients with IDH mutant gliomas. Methods: TEX produced by patient-derived IDH1(mut) or IDH1(wt) glioma spheres or TEX in patient’s plasma were isolated by mini size exclusion chromatography (mini-SEC). TEX morphology, size, numbers and molecular profile were characterized and the crossing of the blood-brain barrier (BBB) and biodistribution was investigated by in vivo imaging of TEX. Interactions of TEX with endothelial cells, astrocytes and immune cells were demonstrated by confocal microscopy. Results: TEX isolated from supernatants of IDH1(mut) or IDH1(wt) glioma spheres by mini-SEC carried TSG101 and showed the typical size and vesicular morphology of exosomes. BCA protein assays and qNano analysis revealed an elevated exosome production by IDH mutant cells ( p&lt; 0.01). TEX carried immunosuppressive proteins (FasL, CTLA-4 and TRAIL) and IDH mutant exosomes carried higher levels of these proteins and of adenosine pathway components CD39 and CD73. Labeled TEX injected in the white matter of mice crossed the BBB and were detectable in distant organs 24h after injection. TEX were rapidly internalized by endothelial cells and astrocytes, but not by T cells, which interacted with TEX by surface signaling. These results were confirmed by investigating TEX isolated from glioma patient’s plasma. Conclusions: The data suggest that TEX play an important role in IDH mutant gliomas and drive tumor progression in part by inducing suppression of immune cells. Future efforts will focus on characterizing immunosuppressive effects of TEX derived from IDH mutant cells vs gliomas without IDH mutations.
Abstract MP012: Plasma Galectin-3 Levels and Subsequent Risk of Incident Chronic Kidney Disease
Authors: Casey M Rebholz, Elizabeth Selvin, Menglu Liang, Christie M Ballantyne, Ron C Hoogeveen, Morgan E Grams, Josef Coresh
Journal: Circulation (2017)

Introduction: Galectin-3 is a 35 kDa β-galactoside-binding lectin which has been proposed as a novel biomarker of heart failure primarily due to its involvement in myocardial fibrosis. Elevated levels of galectin-3 may be associated with fibrosis of other organs, such as the kidney, and increase the risk of developing kidney disease. Methods: Using Cox proportional hazards regression, we prospectively analyzed Atherosclerosis Risk in Communities (ARIC) study participants with measurements of plasma galectin-3 levels at baseline (visit 4, 1996-98) and without prevalent kidney disease or heart failure (N=9,647). Incident chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) &lt;60 mL/min/1.73 m 2 accompanied by 25% eGFR decline, chronic kidney disease-related hospitalization or death, or end-stage renal disease between baseline and December 31, 2013. Results: 2,105 participants (22%) developed incident chronic kidney disease over a median follow-up of 16 years. The mean (standard deviation) plasma level of galectin-3 was 14.7 (4.4) ng/mL. At baseline, galectin-3 was cross-sectionally associated with eGFR (r = -0.31) and urine albumin-to-creatinine ratio (UACR) (r = 0.19). After adjusting for demographics and kidney disease risk factors, there was a significant, graded, and positive association between galectin-3 and incident chronic kidney disease (quartile 4 vs. 1 HR: 1.84, 95% CI: 1.62, 2.09, p for trend &lt;0.001). The association between galectin-3 and incident chronic kidney disease was attenuated but remained significant after accounting for eGFR and UACR (quartile 4 vs. 1 HR: 1.58, 95% CI: 1.39, 1.80, p for trend &lt;0.001). The association was similar by diabetes status (p for interaction = 0.33) and stronger among those with hypertension (p for interaction = 0.004). Conclusion: In this community-based population, higher plasma galectin-3 levels were associated with elevated risk of developing incident chronic kidney disease, particularly among those with hypertension.
RETRACTED ARTICLE: Genetic manipulation of autonomic nerve fiber innervation and activity and its effect on breast cancer progression
Authors: Atsunori Kamiya, Yohsuke Hayama, Shigeki Kato, Akihiko Shimomura, Takushi Shimomura, Katsumasa Irie, Ryosuke Kaneko, Yuchio Yanagawa, Kazuto Kobayashi, Takahiro Ochiya
Journal: Nature Neuroscience (2019)
Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial
Authors: Olga C Aroniadis, Lawrence J Brandt, Caterina Oneto, Paul Feuerstadt, Alex Sherman, Allan W Wolkoff, Zain Kassam, Rotem Gura Sadovsky, Ryan J Elliott, Shrish Budree, Mimi Kim, Marla J Keller
Journal: The Lancet. Gastroenterology & hepatology (2019)
Rammya Mathew: Supporting women in leadership matters
Authors: Rammya Mathew
Journal: BMJ (2019)

I’ve recently been thinking about why men and women enjoy vastly different levels of financial reward in their jobs. It’s particularly difficult to explain in medicine, which is, by and large, a career with a well defined trajectory and non-negotiable pay scales. Trying to unpick this is not straightforward. At first glance it seems to be down to fewer women being in leadership positions: isn’t it scandalous that 77% of the NHS workforce are now female, yet they hold only 37% of senior jobs?1

Are women less excellent? Are they inherently bad at …
Hepatitis B screening rates and reactivation in solid organ malignancy patients undergoing chemotherapy in Southern Thailand
Authors: Ratchapong Laiwatthanapaisan, Pimsiri Sripongpun, Naichaya Chamroonkul, Arunee Dechaphunkul, Chirawadee Sathitruangsak, Siwat Sakdejayont, Chanon Kongkamol, Teerha Piratvisuth
Journal: Clinical and Molecular Hepatology (2019)

Hepatitis B virus reactivation (HBVr) following chemotherapy (CMT) is well-known among hematologic malignancies, and screening recommendations are established. However, HBVr data in solid organ malignancy (SOM) patients are limited. This study aims to determine hepatitis B surface antigen (HBsAg) screening rates, HBV prevalence, and the rate of significant hepatitis caused by HBVr in SOM patients undergoing CMT.Based on the Oncology unit's registration database from 2009-2013, we retrospectively reviewed records of all SOM patients ≥18 years undergoing CMT at Songklanagarind Hospital who were followed until death or ≥6 months after CMT sessions. Exclusion criteria included patients without baseline liver function tests (LFTs) and who underwent CMT before the study period. We obtained and analyzed baseline clinical characteristics, HBsAg screening, and LFT data during follow-up.Of 3,231 cases in the database, 810 were eligible. The overall HBsAg screening rate in the 5-year period was 27.7%. Screening rates were low from 2009-2012 (7.8-21%) and increased in 2013 to 82.9%. The prevalence of HBV among screened patients was 7.1%. Of those, 75% underwent prophylactic antiviral therapy. During the 6-month follow-up period, there were three cases of significant hepatitis caused by HBVr (4.2% of all significant hepatitis cases); all were in the unscreened group.The prevalence of HBV in SOM patients undergoing CMT in our study was similar to the estimated prevalence in general Thai population, but the screening rate was quite low. Cases of HBVr causing significant hepatitis occurred in the unscreened group; therefore, HBV screening and treatment in SOM patients should be considered in HBV-endemic areas.
Abstract P045: Trajectory of Fasting Blood Glucose From Childhood to Adulthood and the Risk of Hypertension: The Bogalusa Heart Study
Authors: Xiang Li
Journal: Circulation (2018)

Background: Hyperglycemia in children or adults has been related to an increased risk of hypertension; however, no study has assessed whether life course trajectory of circulating fasting glucose levels, from childhood to adulthood, is related to hypertension risk. Objective: In the present study, we aim to characterize trajectories of fasting blood glucose (FBG) from childhood to adulthood, and assess their associations with risk of hypertension in the Bogalusa Heart Study. Design: Prospective analysis of 1747 children with &gt;= 4 FBG measurements, of which at least 1 measurement was in childhood (from 4-19 years) and at least 1 measurement in adulthood, during an average of 23.5 years of follow-up. Mixed models were used to test the effect of FBG trajectories on the risk of hypertension. Result: Four distinct trajectories of FBG from childhood to adulthood were identified: constant low, low to high, high to low, and constant high (Figure 1). In multivariate model adjusting for baseline age, race, sex, BMI, adulthood blood pressure, smoking, drinking, physical activity, education, and lipids, the risk of hypertension was 1.12 (95% CI: 1.04 to 1.20; p=0.002) in the low to high group compared to constant low group, 1.02 (95% CI: 0.97 to 1.08; p=0.255) in the high to low group, and 1.10 (95% CI: 1.03 to 1.18; p=0.004) in the constant high group. After further controlling for one-time FBG, especially the adulthood FBG, the effect of trajectories still persist. Conclusion: We identified four different trajectories of FBG from childhood to adulthood, which shows having diverse relationships with hypertension in adulthood.
Abstract 19719: Physical Activity and Risk of Heart Failure With Preserved or Reduced Ejection Fraction in the Women’s Health Initiative Study
Authors: Charles B Eaton, Joseph C Larson, Andrea K Chomistek, JoAnn E Manson, Wenjun Li, Cora E Lewis, Jennifer W Bea, Karen C Johnson, Jean Wactawski-Wende, Michael J LaMonte
Journal: Circulation (2016)

Background: Heart failure (HF) burden is large and growing among older women. Although physical activity (PA) has consistently been associated with lower HF risk in cohort studies, it is unclear wh...
FRI0180 Paraneoplasic antiphospholipid syndrome- a possible main cause of thrombosis in cancer patients
Authors: C Tanaseanu, S Tanaseanu, A Urban, M Popescu, D Hanganu, A Cojan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The antiphospholipid (APS) is a hypercoagulable state marked by the antibodies that recognise anionic phospholipid-protein cofactor complexes. <h3>Objectives</h3> This study was undertaken to investigate a possible association of antiphospholipid antibodies (APLA) in cancer patients with thromboembolic events. <h3>Methods</h3> The study group included 46 patients with different malignancies and associated thromboses. Tests were performed for detecting APLA: anticardiolipin enzyme ?linked immunoassay (ELISA) for both IgG and IgM isotypes, antiâ2-GPI IgG antibody ELISA, and coagulation test for lupus anticoagulant (LAC). We used ACL method with IL Test LAC Screen and IL Test LAC Confirm. All patients underwent complete clinical and radiological examination, routine laboratory tests were done. <h3>Results</h3> 18 patients had APS associated with evolutive cancers. LAC was present in 14 patients (B-cell lymphoma (2 cases), ovarian-(3), breast-(3), lung-(4), pancreatic-(1), bladder (1) cancer, and was related mainly with deep vein thromboses of the legs, pulmonary embolism and catastrophic antiphospholipid syndrome. Anticardiolipin antibodies (ACLA) were detected in 3 patients with bladder -, pancreatic – and breast cancer, and were associated with aortic nonocclusive thrombosis, stroke, myocardial infarction and multiinfarct dementia. In one patient (prostatic cancer) were present both ACLA and LAC, associated with stroke, myocardial infarction, multiinfarct dementia. The presence of LAC seems to be related more to venous thromboses and metastatic disease, while ACLA seems to be related to arterial thromboses. <h3>Conclusion</h3> The presence of APS in cancer patients is associated with vascular thromboses, leading to a poor quality of life or to fatal events (including metastatic spread). The presence of APLA in cancer patients may be a warning sign of a thrombotic event and might lead to a better selection of patients for prophylactic anticoagulant therapy.
Detailed hair shaft analysis in a man with delayed‐onset Chediak‐Higashi syndrome
Authors: O. Veraitch, L. Allison, G. Vizcay‐Barrena, R.A. Fleck, A. Price, D.A. Fenton, J.A. McGrath, C.M. Stefanato
Journal: British Journal of Dermatology (2019)
Adoptive T-Cell Therapy with 3rd Party CMV-pp65-Specific CTLs for CMV Viremia and Disease Arising after Allogeneic Hematopoietic Stem Cell Transplant
Authors: Susan Prockop, Ekaterina Doubrovina, Irene Rodriguez-Sanchez, Aisha N. Hasan, Juliet Barker, H.R. Castro-Malaspina, Parastoo B. Dahi, Sergio A. Giralt, Boglarka Gyurkocza, Nancy A. Kernan, Guenther Koehne, Esperanza B. Papadopoulos, Doris Ponce, Craig S. Sauter, Virginia Escobedo, Victoria Szenes, Karim Baroudy, Alison Slocum, Richard J. O'Reilly
Journal: Blood (2017)
Survival outcomes of patients with peripheral T-cell lymphomas (PTCL) treated with chemotherapy and/or novel agents: The Columbia University experience.
Authors: Helen Ma, Bin Cheng, Owen A. O'Connor
Journal: Journal of Clinical Oncology (2019)

e19049 Background: CHOP-based regimens have been considered the standard of care for PTCL despite disappointing results. Several lines of evidence, including the regulatory approval of novel drugs since 2009, raise the question as to whether these drugs are changing the natural history of relapsed PTCL. Recent molecular insights into the pathogenesis of PTCL, especially in angioimmunoblastic T-cell lymphoma (AITL), have revealed a number of genetic lesions that might portend a unique vulnerability to select agents, such as histone deacetylase inhibitors (HDACi). Methods: This is a retrospective study of patients with PTCL who were seen and treated between 1994 and 2018. Kaplan-Meier curves for overall survival were generated and compared based on the log-rank test. Cox proportional hazard models were used to investigate the association by adjusting for age, gender, subtype, prognostic score and type of treatment. The analysis was done in SAS version 9.4. A p-value &lt; 0.05 was considered statistically significant. Results: At Columbia University Medical Center, a total of 186 patients with PTCL were identified. Excluding patients with incomplete data, 168 patients were analyzed. The median overall survival was 7.5 months (95% CI 5.6-8.9) for the whole study group. Cox modeling adjusted for the aforementioned variables found little impact from the novel agents on the natural history of the disease. In particular, among patients with AITL, no survival benefit was associated with any HDACi. In addition, these data demonstrated that patients with adult T-cell leukemia lymphoma (ATLL) had a better overall survival compared to other subgroups, p = 0.0097. Conclusions: These data are concordant with other large experiences noting the poor prognosis of patients with PTCL, and in particular, those with relapsed disease. The lack of impact of HDACi on the natural history of AITL raises issues about the role of these drugs in this disease. We will present a variety of subanalyses to identify prognostic factors in PTCL. [Table: see text]
Diverse immunotherapies can effectively treat syngeneic brainstem tumors in the absence of overt toxicity
Authors: Matthew R. Schuelke, Phonphimon Wongthida, Jill Thompson, Timothy Kottke, Christopher B. Driscoll, Amanda L. Huff, Kevin G. Shim, Matt Coffey, Jose Pulido, Laura Evgin, Richard G. Vile
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Immunotherapy has shown remarkable clinical promise in the treatment of various types of cancers. However, clinical benefits derive from a highly inflammatory mechanism of action. This presents unique challenges for use in pediatric brainstem tumors including diffuse intrinsic pontine glioma (DIPG), since treatment-related inflammation could cause catastrophic toxicity. Therefore, the goal of this study was to investigate whether inflammatory, immune-based therapies are likely to be too dangerous to pursue for the treatment of pediatric brainstem tumors. <h3>Methods</h3> To complement previous immunotherapy studies using patient-derived xenografts in immunodeficient mice, we developed fully immunocompetent models of immunotherapy using transplantable, syngeneic tumors. These four models – HSVtk/GCV suicide gene immunotherapy, oncolytic viroimmunotherapy, adoptive T cell transfer, and CAR T cell therapy – have been optimized to treat tumors outside of the CNS and induce a broad spectrum of inflammatory profiles, maximizing the chances of observing brainstem toxicity. <h3>Results</h3> All four models achieved anti-tumor efficacy in the absence of toxicity, with the exception of recombinant vaccinia virus expressing GMCSF, which demonstrated inflammatory toxicity. Histology, imaging, and flow cytometry confirmed the presence of brainstem inflammation in all models. Where used, the addition of immune checkpoint blockade did not introduce toxicity. <h3>Conclusions</h3> It remains imperative to regard the brainstem with caution for immunotherapeutic intervention. Nonetheless, we show that further careful development of immunotherapies for pediatric brainstem tumors is warranted to harness the potential potency of anti-tumor immune responses, despite their possible toxicity within this anatomically sensitive location.
HIV-associated high-risk HPV infection in Nigerian women.
Authors: Sally Nneoma Akarolo-Anthony, Celestine C. Ogbonna, Oluranti Ayotunde Famooto, Eileen O. Dareng, Maryam Al-Mujtaba, George Odonye, Olayinka Olaniyan, Richard Offiong, Ishak Lawal, Cosette Wheeler, Clement Adebayo Adebamowo
Journal: Journal of Clinical Oncology (2013)

1576 Background: The incidence of cervical cancer has remained stable in HIV+ women but the prevalence and multiplicity of high risk HPV (hrHPV) infection, a necessary cause of cervical cancer, appears different comparing HIV+ to HIV- women. Because this has not been well studied in Africa, we conducted this study to identify single and multiple hrHPV infection among HIV+ and HIV- women in Nigeria. Methods: We enrolled HIV+ and HIV- women presenting at our cervical cancer screening program in Abuja, Nigeria between April 2012 and August 2012. Using a nurse administered questionnaire, we collected information on demographic characteristics, risk factors of HPV infection and cervical exfoliated cells samples from all participants. We used Roche Linear Array HPV Genotyping Test to characterize the prevalent HPV according to manufacturer’s instruction and logistic regression models to estimate the association between HIV infection and the risk of high-risk HPV infection. Results: There were 278 participants, 40% (111) of whom were HIV negative, 54% (151) HIV positive and 6% (16) with HIV status unknown. Of these, 108 HIV+ women cases and 149 HIV- women controls were available for analysis. The mean ages (±SD) were 37.6 (±7.7) for HIV+ and 36.6 (±7.9) years for HIV- women (p-value = 0.34). Cases and controls had similar socio-demographic characteristics. Among HIV+ women, HPV35 (8.7%) and HPV56 (7.4%) were the most prevalent hrHPV, while HPV52 and HPV68 (2.8%, each) were the most prevalent among HIV- women. The age adjusted RR for prevalent hrHPV was 4.18 (95% CI 2.05 – 8.49, p-value &lt;0.0001), comparing HIV+ to HIV- women. The multivariate RR for any HPV and multiple hrHPV was 3.75 (95% CI 2.08 – 6.73, p-value 0.01) and 6.6 (95% CI 1.49 – 29.64, p-value 0.01) respectively, comparing HIV+ to HIV- women, adjusted for age, and educational level. Conclusions: HIV infection was associated with increased risk of any HPV, hrHPV and multiple HPV infections. Oncogenic HPV types 35, 52, 56 and 68 may be more important risk factors for cervical pre-cancer and cancer among women in Africa. Polyvalent hrHPV vaccines meant for African populations should protect against HPV types other than 16 and 18.