tbuckley/cabot-search huggingface dataset:
Outcomes of newly diagnosed myeloma patients requiring dialysis: renal recovery, importance of rapid response and survival benefit
Authors: M A Dimopoulos, M Roussou, M Gavriatopoulou, D Fotiou, D C Ziogas, M Migkou, I Panagiotidis, E Eleutherakis-Papaiakovou, N Kanellias, E Psimenou, S Marinaki, D Bacharaki, D Mparmparoussi, C Matsouka, S Giannouli, E Terpos, E Kastritis
Journal: Blood Cancer Journal (2017)

] Immediate effective anti-myeloma therapy and vigorous supportive care are the cornerstones of management. 2-3][6][7][8] Moreover, the use of high cut-off hemodialysis to rapidly reduce the load of nephrotoxic light chains may provide some additional benefit in patients requiring dialysis when treated with bortezomib-based therapies, but the reported results of two randomized studies are controversial. 9-10Thus, we analyzed the outcomes of 52 consecutive NDMM with RI requiring dialysis, which were managed and treated in a single center, to provide data on response to therapy, dialysis discontinuation and survival in unselected patients, outside the context of clinical trials.The analysis included 52 patients (6.2% of 796 consecutive NDMM) who were treated in the Department of Clinical Therapeutics, and which presented with severe renal failure requiring dialysis, between January 1995 and January 2016.An approval for data collection and publication was obtained by the Alexandra Hospital Scientific Committee.The analysis included all patients who received at least one dose of any therapy.All patients received similar supportive care and dialysis with regular filters.Patients with light-chain amyloidosis, light-chain deposition disease or previously under dialysis due to causes other than myeloma were excluded from the analysis.Renal response was defined as independence from dialysis and discontinuation of this procedure.Myeloma response and progression followed International Myeloma Working Group definitions. 11Time to renal recovery (renal response) was calculated from the date of initiation of therapy until the date of the last dialysis session.Survival was calculated from the date of first dose of therapy until the date of last follow-up or death.The median age of patients requiring dialysis was 69 years (range 37-88), and 68% were 465 years of age; their characteristics are shown in Table 1.High-risk cytogenetics (available in 40 patients) were present in 38%, thus, per revised International Staging System, 75% were revised International Staging System-3 and the rest revised International Staging System-2.Among patients who retained urine flow at presentation, median 24 h Bence Jones proteinuria was 2.2 gr (range 0.1-8.8).Among patients with available Free light chains, median level of involved free-light chain (iFLC) was 9080 mg/l (range 1190-201 000 mg/l) (Table 1).Treatment was bortezomib-based in 43 (82%) patients: 11 (21%) received bortezomib with dexamethasone (VD), 23 (44%) VD plus cyclophosphamide (VCD), 8 (15%) VD plus thalidomide (VTD), 1 (2%) received VD plus doxorubicin Blood Cancer Journal
Predictors of unplanned hospitalizations among older adults receiving cancer chemotherapy.
Authors: Heidi D. Klepin, Can-Lan Sun, David D Smith, Rawad Elias, Kelly Marie Trevino, Ashley Leak Bryant, Christian J Nelson, William P. Tew, Supriya Gupta Mohile, Cynthia Owusu, Cary Philip Gross, Ajeet Gajra, Stuart M. Lichtman, Vani Katheria, Arti Hurria
Journal: Journal of Clinical Oncology (2016)

10057 Background: Older patients with cancer are at increased risk of hospitalizations during cancer treatment. Our objective was to identify risk factors for unplanned hospitalization among older adults receiving chemotherapy. Methods: We conducted a secondary analysis of a multi-site cohort study (N = 500) of patients ≥ 65 years evaluated with a geriatric assessment (GA) to predict chemotherapy toxicity. The primary outcome wasincident toxicity-related hospitalization during treatment. Predictor variables included: 1) pretreatment GA measures assessing functional status (self-reported and objectively measured), falls, self-reported co-morbidity, mood, social activity and support, nutrition, cognition, and polypharmacy; 2) baseline laboratory values (creatinine clearance [CrCl] by Cockcroft-Gault, hemoglobin, albumin); 3) cancer type and stage; and 4) treatment (mono vs. poly-chemotherapy and dosing). Logistic regression was used to estimate the odd ratio (OR) of hospitalization in multivariate analyses. Results: Among 500 subjects, 117 (23.4%) experienced one or more unplanned hospitalizations during receipt of chemotherapy. Hospitalized subjects were older (74.2 vs. 72.8 years, p = 0.02), more likely to have: a high school or lower education (p = 0.02); a gastrointestinal malignancy (p < 0.001); lower Karnofsky performance status (p = 0.02); polypharmacy ( ≥ 4 medications, p = 0.02); lower instrumental activity of daily living scores (p = 0.03); more comordid conditions (p < 0.001); lower albumin (p < 0.001); and lower CrCl (p = 0.001). In multivariate analyses controlling for cancer type, increased odds of hospitalization was associated with greater number of comorbid conditions (OR = 1.3, 95% Confidence Interval [CI] 1.1-1.5), lower baseline CrCl (OR 1.2, CI 1.1-1.3 per 10 mL/min decrease), and lower baseline albumin (OR 2.7, CI 1.8-4.2 per 1gm/dl decrease), p < 0.001 for all. Conclusions: Readily available information, including self-reported comorbidity, albumin and CrCl, was associated with toxicity-related hospitalizations among older adults receiving chemotherapy. If validated, these data can inform prediction models and interventions designed to decrease hospitalizations.
Delayed Necrosectomy Improves Outcome in Severe Necrotising Pancreatitis
Authors: C Moran, JB Conneely, M Doyle, D Maguire, D Phelan, E Carton, B Marsh, F Colreavy, M McNicholas, H Fenlon, J Murray, GP McEntee
Journal: Endoscopy (2004)

Aim: Current practice of early necrosectomy in cases of infected pancreatic necrosis is associated with 30–35% mortality. The aim of our study was to determine outcome where pancreatic necrosectomy (PN) is delayed.
The US President’s Malaria Initiative and under-5 child mortality in sub-Saharan Africa: A difference-in-differences analysis
Authors: Aleksandra Jakubowski, Sally C. Stearns, Margaret E. Kruk, Gustavo Angeles, Harsha Thirumurthy
Journal: PLoS Medicine (2017)

Despite substantial financial contributions by the United States President's Malaria Initiative (PMI) since 2006, no studies have carefully assessed how this program may have affected important population-level health outcomes. We utilized multiple publicly available data sources to evaluate the association between introduction of PMI and child mortality rates in sub-Saharan Africa (SSA).We used difference-in-differences analyses to compare trends in the primary outcome of under-5 mortality rates and secondary outcomes reflecting population coverage of malaria interventions in 19 PMI-recipient and 13 non-recipient countries between 1995 and 2014. The analyses controlled for presence and intensity of other large funding sources, individual and household characteristics, and country and year fixed effects. PMI program implementation was associated with a significant reduction in the annual risk of under-5 child mortality (adjusted risk ratio [RR] 0.84, 95% CI 0.74-0.96). Each dollar of per-capita PMI expenditures in a country, a measure of PMI intensity, was also associated with a reduction in child mortality (RR 0.86, 95% CI 0.78-0.93). We estimated that the under-5 mortality rate in PMI countries was reduced from 28.9 to 24.3 per 1,000 person-years. Population coverage of insecticide-treated nets increased by 8.34 percentage points (95% CI 0.86-15.83) and coverage of indoor residual spraying increased by 6.63 percentage points (95% CI 0.79-12.47) after PMI implementation. Per-capita PMI spending was also associated with a modest increase in artemisinin-based combination therapy coverage (3.56 percentage point increase, 95% CI -0.07-7.19), though this association was only marginally significant (p = 0.054). Our results were robust to several sensitivity analyses. Because our study design leaves open the possibility of unmeasured confounding, we cannot definitively interpret these results as causal.PMI may have significantly contributed to reducing the burden of malaria in SSA and reducing the number of child deaths in the region. Introduction of PMI was associated with increased coverage of malaria prevention technologies, which are important mechanisms through which child mortality can be reduced. To our knowledge, this study is the first to assess the association between PMI and all-cause child mortality in SSA with the use of appropriate comparison groups and adjustments for regional trends in child mortality.
Distinction between double primary lung cancer and intrapulmonary metastasis using a system for profiling the DNA methylation status of multiple gene promoters
Authors: Atsushi Sano, Hidenori Kage, Keiki Sugimoto, Hiroshi Kitagawa, Naomi Aki, Akiteru Goto, Masashi Fukayama, Jun Nakajima, Shinichi Takamoto, Takahide Nagase, Yutaka Yatomi, Nobuya Ohishi, Daiya Takai
Journal: Cancer Research (2007)

1781   Patients who have two lung cancers simultaneously are occasionally seen. Distinguishing double primary lung cancers from a single cancer with intrapulmonary metastasis using pathological methods is often difficult even though the prognosis is entirely different. To display the difference in clonality between the two lesions in such cases, we have applied a system for profiling the methylation status of multiple gene promoters. It is based on bisulfite reaction of DNA and real-time PCR using two probes labeled with different fluorescence, followed by clustering analysis. PCR primers were set at CpG-less sites. For discrimination between methylated and unmethylated alleles with high-fidelity, we used TaqMan MGB probes. Using 10 promoters, 90 primary lung cancers were clustered into several groups consisting of cases having similar clinical backgrounds and pathological findings. Eight cancers were double cancers from four patients. In two patients, the two cancers had the same methylation profiles and belonged to the same cluster. Therefore we could make the diagnosis as a single cancer with intrapulmonary metastasis. In the remaining two patients, the methylation profile of the two cancers differed and belonged to different clusters. Therefore, we could make the diagnosis as double primary lung cancers. In one of those patients, both cancers were moderately differentiated squamous cell carcinoma, and it was pathologically impossible to distinguish double primary lung cancers from a single cancer with intrapulmonary metastasis. However, the methylation profile of the two cancers differed, and we could make the diagnosis as double primary lung cancers. These findings indicate that the addition of our method is more precise than conventional methods, and is especially useful for the diagnosis of clonality.
A Central Catecholaminergic Circuit Controls Blood Glucose Levels during Stress
Authors: Zhe Zhao, Liang Wang, Wenling Gao, Fei Hu, Juen Zhang, Yuqi Ren, Rui Lin, Qiru Feng, Mingxiu Cheng, Dapeng Ju, Qingsheng Chi, Dehua Wang, Sen Song, Minmin Luo, Cheng Zhan
Journal: Neuron (2017)
Suppression by human FOXP3 <sup>+</sup> regulatory T cells requires FOXP3-TIP60 interactions
Authors: Khalid Bin Dhuban, Eva d’Hennezel, Yasuhiro Nagai, Yan Xiao, Steven Shao, Roman Istomine, Fernando Alvarez, Moshe Ben-Shoshan, Hans Ochs, Bruce Mazer, Bin Li, Chiyoko Sekine, Alan Berezov, Wayne Hancock, Troy R. Torgerson, Mark I. Greene, Ciriaco A. Piccirillo
Journal: Science Immunology (2017)

Targeting the FOXP3-TIP60 interaction may modulate T reg activity in IPEX and other autoimmune and inflammatory diseases.
Abstract 87: The Impact of Coxsackievirus Infection on Cardiac Stem Cells and Postnatal Heart Development
Authors: JonSin, JennaTabor Godwin, ChengqunHuang, Roberta AGottlieb, RalphFeuer
Journal: Circulation Research (2012)

Coxsackievirus B (CVB) is an enterovirus that causes a self-limited febrile illness in infants, but can also cause myocarditis. Long-term consequences of mild CVB infection are unknown, although an association between heart failure and seropositive status has been previously described. We have shown that early postnatal exposure to doxorubicin depleted c-Kit+ cardiac stem cells (CSCs). Cardiac dysfunction in adult mice only developed after exercise challenge, or experimentally-induced myocardial infarction. We now report that CSCs from neonatal mouse hearts were susceptible to cytopathic CVB infection. To learn if mild CVB infection might deplete the CSC population in the heart, we inoculated newborn BALB/c mice with a recombinant CVB expressing eGFP. We observed CVB-infected CSCs 2 days post-inoculation and documented a reduction in the number of c-Kit+ cells in the hearts of animals at 4 and 11 weeks of age despite the absence of detectable virus. Moreover, CVB infection induced differentiation in the surviving CSCs. These results indicate that CVB can infect CSCs in the neonatal heart and trigger their destruction. Premature differentiation of surviving cells may also explain the reduced CSC population in adult mice. Despite normal histologic features in adult hearts, prolonged exercise challenge elicited cardiac hypertrophy and fibrosis in mice infected with CVB as pups. We suggest that the loss of CSCs after mild neonatal CVB infection may predispose to late-onset heart failure.
Phase I Dose-Escalation and -Expansion Study of the BRAF Inhibitor Encorafenib (LGX818) in Metastatic <i>BRAF</i>-Mutant Melanoma
Authors: Jean-Pierre Delord, Caroline Robert, Marta Nyakas, Grant A. McArthur, Ragini Kudchakar, Amit Mahipal, Yasuhide Yamada, Ryan Sullivan, Ana Arance, Richard F. Kefford, Matteo S. Carlino, Manuel Hidalgo, Carlos Gomez-Roca, Daniela Michel, Abdelkader Seroutou, Vassilios Aslanis, Giordano Caponigro, Darrin D. Stuart, Laure Moutouh-de Parseval, Tim Demuth, Reinhard Dummer
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Encorafenib, a selective BRAF inhibitor (BRAFi), has a pharmacologic profile that is distinct from that of other clinically active BRAFis. We evaluated encorafenib in a phase I study in patients with BRAFi treatment-naïve and pretreated BRAF-mutant melanoma. Experimental Design: The pharmacologic activity of encorafenib was first characterized preclinically. Encorafenib monotherapy was then tested across a range of once-daily (50–700 mg) or twice-daily (75–150 mg) regimens in a phase I, open-label, dose-escalation and -expansion study in adult patients with histologically confirmed advanced/metastatic BRAF-mutant melanoma. Study objectives were to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D), characterize the safety and tolerability and pharmacokinetic profile, and assess the preliminary antitumor activity of encorafenib. Results: Preclinical data demonstrated that encorafenib inhibited BRAF V600E kinase activity with a prolonged off-rate and suppressed proliferation and tumor growth of BRAF V600E–mutant melanoma models. In the dose-escalation phase, 54 patients (29 BRAFi-pretreated and 25 BRAFi-naïve) were enrolled. Seven patients in the dose-determining set experienced dose-limiting toxicities. Encorafenib at a dose of 300 mg once daily was declared the RP2D. In the expansion phase, the most common all-cause adverse events were nausea (66%), myalgia (63%), and palmar–plantar erythrodysesthesia (54%). In BRAFi-naïve patients, the overall response rate (ORR) and median progression-free survival (mPFS) were 60% and 12.4 months [95% confidence interval (CI), 7.4–not reached (NR)]. In BRAFi-pretreated patients, the ORR and mPFS were 22% and 1.9 months (95% CI, 0.9–3.7). Conclusions: Once-daily dosing of single-agent encorafenib had a distinct tolerability profile and showed varying antitumor activity across BRAFi-pretreated and BRAFi-naïve patients with advanced/metastatic melanoma. Clin Cancer Res; 23(18); 5339–48. ©2017 AACR.
Authors’ reply to Rishniw
Authors: Sarah C Markt, Lorelei A Mucci
Journal: BMJ (2017)

Rishniw raises a potential concern about “perception v production” of asparagus odorant in urine—that is, whether there is variation in the ability to produce the odorant after consumption of asparagus or in the ability to smell it.12 We focused on the ability to produce it, and a limitation of our study was that we were unable to objectively evaluate the urine samples in our population based cohort study for the remnants of asparagus consumption.

Previous studies have shown differences in both production …
Analysis of Clinicopathological Factors Predicting Response to Neoadjuvant Chemoradiotherapy in Oesophageal Cancer
Authors: M MacGuill, E Mulligan, N Ravi, JV Reynolds
Journal: Endoscopy (2004)

Multimodality therapy comprising neoadjuvant chemotherapy and radiation therapy prior to radical resection is increasingly utilised in oesophageal cancer. The achievement of a complete pathological response (pCR) or a major response is associated with an improved survival. Between 50 and 70% of patients, however, show no response to the neoadjuvant regimen and accordingly the identification of factors which predict a response to chemoradiotherapy would be of considerable clinical benefit. We investigated the following clinicopathological factors: demographics, social history, clinical history, tumour type, site, size, morphology and differentiation.
Carboplatin and Etoposide With or Without Palifosfamide in Untreated Extensive-Stage Small-Cell Lung Cancer: A Multicenter, Adaptive, Randomized Phase III Study (MATISSE)
Authors: Shadia I. Jalal, Philip Lavin, Gregory Lo, Francois Lebel, Lawrence Einhorn
Journal: Journal of Clinical Oncology (2017)

Purpose To evaluate the efficacy of the addition of palifosfamide to carboplatin and etoposide in extensive stage (ES) small-cell lung cancer (SCLC). Patients and Methods MATISSE was a randomized, open-label, adaptive phase III study. Previously untreated patients with ES SCLC were randomly assigned in a 1:1 fashion to receive carboplatin at area under the serum concentration-time curve 5 on day 1 plus etoposide 100 mg/m2 per day on days 1 to 3 every 21 days (CE) or carboplatin at area under the serum concentration-time curve 4 on day 1 plus etoposide 100 mg/m2 per day plus palifosfamide 130 mg/m2 per day on days 1 to 3 every 21 days (PaCE). The primary end point was overall survival. Results In all, 188 patients were enrolled; 94 patients received CE and 94 patients received PaCE. The median age on both arms was 61 years. Six cycles of chemotherapy were completed on both arms of the study by approximately 50% of the patients. Serious adverse events were documented and did not differ significantly between patients receiving PaCE and those receiving CE. Median overall survival was similar between both arms with 10.03 months on PaCE and 10.37 months on CE ( P = .096). Conclusion The addition of palifosfamide to CE failed to improve survival in ES SCLC.
Structural priming and the representation of language
Authors: Holly P. Branigan, Martin J. Pickering
Journal: Behavioral and Brain Sciences (2017)

Abstract Structural priming offers a powerful method for experimentally investigating the mental representation of linguistic structure. We clarify the nature of our proposal, justify the versatility of priming, consider alternative approaches, and discuss how our specific account can be extended to new questions as part of an interdisciplinary programme integrating linguistics and psychology as part of the cognitive sciences of language.
Childhood and Adolescent Obesity as a Winnable Battle—Reply
Authors: Thomas R. Frieden, Kathleen Ethier
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Critical role of CREBH‐mediated induction of transforming growth factor β2 by hepatitis C virus infection in fibrogenic responses in hepatic stellate cells
Authors: Takeshi Chida, Masahiko Ito, Kenji Nakashima, Yumi Kanegae, Takuya Aoshima, Shuji Takabayashi, Kazuhito Kawata, Yoshimi Nakagawa, Masahiro Yamamoto, Hitoshi Shimano, Tomokazu Matsuura, Yoshimasa Kobayashi, Takafumi Suda, Tetsuro Suzuki
Journal: Hepatology (2017)

Mechanisms of hepatic fibrogenesis induced by hepatitis C virus (HCV), one of the leading causes of liver fibrosis, are not fully understood. We studied transcriptional up‐regulation of transforming growth factor β (TGF‐β), especially TGF‐β2, which is mediated by activation of liver‐enriched transcription factor cAMP‐responsive element‐binding protein, hepatocyte specific (CREBH) triggered by HCV infection and its functional significance for induction of profibrogenic phenotypes by interaction of HCV‐infected cells with hepatic stellate cells (HSCs). Compared to TGF‐β1, expression of TGF‐β2 mRNA was induced faster and to a higher level upon HCV infection. Serum TGF‐β2 levels in hepatitis C patients were higher compared to those in healthy individuals and were positively correlated with hepatic fibrosis stages F0‐F2. TGF‐β2 promoter activity was decreased and increased, respectively, by silencing and overexpression of CREBH. CREBH recognition sites were identified in the TGF‐β2 promoter. CREBH binding to the promoter and its increase in cells expressing HCV Core‐NS2 were shown by gel mobility shift and chromatin immunoprecipitation, respectively. The active form of CREBH was detectable in HCV‐infected chimeric mice with human livers and cells expressing HCV proteins. Involvement of CREBH in HCV‐induced fibrogenic response was further demonstrated in the CREBH null‐mutant mouse model. Fibrogenic phenotypes were assessed using co‐cultures of HCV‐infected cells and HSCs. Expressions of fibrogenic factors and TGF‐β1 increasing in the co‐cultures was prevented by TGF‐β2‐ or CREBH silencing. Conclusion : CREBH was identified as a key positive regulator of TGF‐β2 transcription in HCV‐infected cells. TGF‐β2 released from infected cells potentially contributes to cross‐induction of TGF‐β in an autocrine manner through its own signaling pathway, leading to an increase in fibrogenic responses in adjacent HSCs. (H epatology 2017;66:1430–1443).