tbuckley/cabot-search huggingface dataset:
Incidence and Associations of Chronic Kidney Disease in Community Participants With Diabetes: A 5-Year Prospective Analysis of the EXTEND45 Study
Authors: Louisa Sukkar, Amy Kang, Carinna Hockham, Tamara Young, Min Jun, Celine Foote, Roberto Pecoits-Filho, Brendon Neuen, Kris Rogers, Carol Pollock, Alan Cass, David Sullivan, Germaine Wong, John Knight, David Peiris, Martin Gallagher, Meg Jardine
Journal: Diabetes Care (2020)

OBJECTIVE To determine the incidence of and factors associated with an estimated glomerular filtration rate (eGFR) &amp;lt;60 mL/min/1.73 m2 in people with diabetes. RESEARCH DESIGN AND METHODS We identified people with diabetes in the EXamining ouTcomEs in chroNic Disease in the 45 and Up Study (EXTEND45), a population-based cohort study (2006–2014) that linked the Sax Institute’s 45 and Up Study cohort to community laboratory and administrative data in New South Wales, Australia. The study outcome was the first eGFR measurement &amp;lt;60 mL/min/1.73 m2 recorded during the follow-up period. Participants with eGFR &amp;lt; 60 mL/min/1.73 m2 at baseline were excluded. We used Poisson regression to estimate the incidence of eGFR &amp;lt;60 mL/min/1.73 m2 and multivariable Cox regression to examine factors associated with the study outcome. RESULTS Of 9,313 participants with diabetes, 2,106 (22.6%) developed incident eGFR &amp;lt;60 mL/min/1.73 m2 over a median follow-up time of 5.7 years (interquartile range, 3.0–5.9 years). The eGFR &amp;lt;60 mL/min/1.73 m2 incidence rate per 100 person-years was 6.0 (95% CI 5.7–6.3) overall, 1.5 (1.3–1.9) in participants aged 45–54 years, 3.7 (3.4–4.0) for 55–64 year olds, 7.6 (7.1–8.1) for 65–74 year olds, 15.0 (13.0–16.0) for 75–84 year olds, and 26.0 (22.0–32.0) for those aged 85 years and over. In a fully adjusted multivariable model incidence was independently associated with age (hazard ratio 1.23 per 5-year increase; 95% CI 1.19–1.26), geography (outer regional and remote versus major city: 1.36; 1.17–1.58), obesity (obese class III versus normal: 1.44; 1.16–1.80), and the presence of hypertension (1.52; 1.33–1.73), coronary heart disease (1.13; 1.02–1.24), cancer (1.30; 1.14–1.50), and depression/anxiety (1.14; 1.01–1.27). CONCLUSIONS In participants with diabetes, the incidence of an eGFR &amp;lt;60 mL/min/1.73 m2 was high. Older age, remoteness of residence, and the presence of various comorbid conditions were associated with higher incidence.
Global survey on barriers to clinical cancer research.
Authors: Tanja Cufer, Eduardo L. Cazap, Lucia Beatriz Delgado, Raghunadharao Digumarti, Natasha B. Leighl, Mohamed M. Meshref, Hironobu Minami, Eliezer Robinson, Nise Hitomi Yamaguchi, Aleksander Sadikov, Bostjan Seruga, Doug Pyle
Journal: Journal of Clinical Oncology (2012)

e16505 Background: Many authorities, including ASCO, have raised concerns about growing barriers to clinical cancer research. We believe this is the first global survey of perceived barriers to clinical cancer research from the investigator perspective. Methods: The ASCO International Affairs Committee invited 300 oncologists in 19 countries to complete a web-based survey. Eighty responded, with 41 from high-income countries (HIC) and 39 from low- and middle-income countries (LMIC). Most responders were medical oncologists (62%), at academic hospitals (90%). Barriers were ranked from 1 (most) to 8 (least) important. Results: Most responders reported participating in academia-driven (ADCT) (92%) and industry-driven clinical trials (IDCT) (89%) in the last 5 years, with a significantly higher proportion from HIC compared to LMIC involved in more than 10 ADCT (71% vs. 29%; p=0.008) and IDCT (71% vs. 29%; p=0.017) in that time. Most of the responders (45% from HIC vs. 55% from LMIC; p=NS) reported “no change” in the last 5 years in the proportion of their trials that were IDCT. Of those who said it has become more difficult to conduct ADCT (40/80) and IDCT (27/80), a significantly higher share came from HIC than from LMIC in the case of both ADCT (29/40; 73% vs. 11/40; 28%; p=0.001) and IDCT (19/27; 70% vs. 8/27; 30%; p=0.009). Average time reported from regulatory initiation to the first-patient-in was up to 90 days for 39% of responders, 90-120 days for 26% and more than 120 days for 30%, with extremes reported most frequently by LMIC responders. A lack of funding was ranked the most important barrier to ADCT by both HIC (3.15) and by LMIC (3.18) responders, and a lack of patients the least important by both HIC (5.27) and LMIC (5.59) responders. LMIC responders considered competent authorities (regulatory) procedures a more important barrier than HIC responders (3.87 vs. 4.67). Conclusions: Though investigators from HIC are involved in more ADCT and IDCT than LMIC counterparts, they are more likely to perceive the barriers to conducting trials as worsening. Of note, no major shift towards greater IDCT was reported in our survey. With regards to ADCT, the main barrier that should be improved globally is financing, with an additional focus in LMIC on regulatory procedures optimization.
Mediterranean diet, gut microbiota and health: when age and calories do not add up!
Authors: Patrice D Cani, Matthias Van Hul
Journal: Gut (2020)

A healthy diet is generally recognised as a diet that supports the physiological and energetic requirements of the body and provides sufficient, though not excessive, amounts of micronutrients and macronutrients. Despite this self-evident definition, the implementation of this basic principle has proven very difficult in modern western society. The benefits of adopting a Mediterranean diet (MedDiet) were already scientifically described more than 50 years ago,1 when a reduction in cardiovascular disease risk was observed among populations whose nutritional habits were consistent with those of people from the Mediterranean basin.2 Today, adherence to a MedDiet has been associated with lower mortality, reductions in obesity, type 2 diabetes, low-grade inflammation, cancer, Alzheimer’s disease and depression, and, more recently, the delayed onset of Crohn’s disease.3–5

Surprisingly, the exact mechanisms of action are not yet fully understood, and various hypotheses have been proposed to explain the potential beneficial effects of the MedDiet. Among them, a presumed link between the MedDiet and the gut microbiota was put forward not more than a few years ago; this idea is therefore considered relatively new.

In GUT , two studies conducted in humans have now made progress towards a better understanding of the role of the gut microbiota and the MedDiet in disease risk factors.6 7

In the first paper, Meslier and colleagues studied healthy overweight or obese subjects with sedentary lifestyles who habitually consumed low amounts of fruits and vegetables during an 8-week follow-up.6 In this randomised controlled study, 43 subjects were assigned to the MedDiet group, in which they received a personalised diet adapted to their habitual energy intake. The remaining 39 subjects continued on their regular diet. Among the different food items proposed to the MedDiet group were fewer meat and refined-cereal products and more fish, fruits, vegetables, legumes and …
AORTIC VALVE CALCIUM SCORE CUT-OFFS USED TO IDENTIFY HEMODYNAMICALLY SEVERE AORTIC STENOSIS MAY NOT APPLY IN PATIENTS WITH CARDIAC AMYLOIDOSIS
Authors: Muzna Hussain, Mazen Hanna, Brian P. Griffin, Jay Patel, Agostina Fava, Chris Watson, Dermot Phelan, Christine Louise Jellis, Richard A. Grimm, Leonardo Rodriguez, Paul Schoenhagen, Rory Hachamovitch, Wael A. Jaber, Paul Cremer, Patrick Collier
Journal: Journal of the American College of Cardiology (2020)
P2Y12 INHIBITOR MONOTHERAPY AFTER A SHORT DUAL ANTIPLATELET THERAPY VS. 12-MONTH DUAL ANTIPLATELET THERAPY IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION: A META-ANALYSIS
Authors: Hua Ling, Ugochukwu Egolum, Shanea Parker, Ai-Chen Ho, Jordan Dimmel, Andrew Hawkins
Journal: Journal of the American College of Cardiology (2020)
Magnetic Nanoparticles in Cancer Therapy and Diagnosis
Authors: Ali Farzin, Seyed Alireza Etesami, Jacob Quint, Adnan Memic, Ali Tamayol
Journal: Advanced Healthcare Materials (2020)

There is urgency for the development of nanomaterials that can meet emerging biomedical needs. Magnetic nanoparticles (MNPs) offer high magnetic moments and surface-area-to-volume ratios that make them attractive for hyperthermia therapy of cancer and targeted drug delivery. Additionally, they can function as contrast agents for magnetic resonance imaging (MRI) and can improve the sensitivity of biosensors and diagnostic tools. Recent advancements in nanotechnology have resulted in the realization of the next generation of MNPs suitable for these and other biomedical applications. This review discusses methods utilized for the fabrication and engineering of MNPs. Recent progress in the use of MNPs for hyperthermia therapy, controlling drug release, MRI, and biosensing is also critically reviewed. Finally, challenges in the field and potential opportunities for the use of MNPs toward improving their properties are discussed.
A CASE OF RECURRENT HIGH-GRADE UNDIFFERENTIATED CARDIAC SARCOMA WITH INVOLVEMENT OF PULMONARY VEINS REQUIRING CARDIAC AUTOTRANSPLANTATION
Authors: Rakushumimarika Harada, Michinari Hieda, Mark Feldman, Yogamaya Mantha, Michael Reardon, Jorge Cheirif
Journal: Journal of the American College of Cardiology (2020)
ADHERENCE TO GUIDELINE-DIRECTED MEDICAL AND DEVICE THERAPY IN HEART FAILURE WITH REDUCED EJECTION FRACTION
Authors: Umut Kocabas, Tarik Kivrak, Gulsum Meral Yilmaz Oztekin, Veysel Ozan Tanik, Ibrahim Ozdemir, Ersin Kaya, Elif Ilkay Yuce, Fulya Avci Demir, Mustafa Dogdus, Seckin Pehlivanoglu
Journal: Journal of the American College of Cardiology (2020)
3D index calculated from duration and severity of neutropenia and a degree of fever as prognostic factors predicting mortality of chemotherapy-induced febrile neutropenia in hematologic malignancies.
Authors: Ryosuke Shirasaki, Nobu Akiyama, Haruko Tashiro, Takuji Matsuo, Tadashi Yamamoto, Yoko Oka, Kazuo Kawasugi, Naoki Shirafuji
Journal: Journal of Clinical Oncology (2012)

9053 Background: Risk stratification of patients with febrile neutropenia (FN) is important to select the suitable therapeutic option. Although the MASCC scoring system is used as a reliable risk-discriminator, the objective evaluation of “burden of illness” has been difficult to be pointed-out. The latest IDSA Guidelines on FN proposes a set of risk factors based on the expert’s recommendations. The present study demonstrates usefulness of newly proposed 3D-index on predicting mortality of chemotherapy-induced FN in hematologic malignancies (HM). Methods: Patients with HM admitted to our hospital between Jan 2008 and Dec 2011 were enrolled, and data from 282 FN episodes in 129 FN patients including 20 infection-associated deaths were retrospectively analyzed to determine useful prognostic factors on the mortality of FN. Correlation between mortality and 59 characteristics including 3D-index were examined by univariate analysis and receiver operating characteristic curve analysis. 3D-index is a duration and severity of neutropenia and degree of fever. Total duration of days during neutropenia was not calculate at the time of risk evaluation. 3D-indexes after three and five days from the start of FN were also analyzed. Results: 32 out of 59 characteristics were significantly correlated with mortality by univariate analysis. Among them, 3D-index and 3D-indexes after three and five days were demonstrated as more useful factors (3D-index, p=0.0015; 3D-index after three days, p=0.0030; 3D-index after five days, p=0.0044). And 3D-index after three days over 4000 indicates patients' mortality above 20%, index 2600-4000 15-20% , index 900-2600 10-15%, and index below 900 below 10%, respectively. Conclusions: 3D-indexes after three days were suggested as useful predictors for infection-related mortality during FN. It was suggested that FN patients were categorized into four risk groups according to the value.
Effect of matrix metalloproteinase-2 on antitumor immunity.
Authors: Emmanuelle Godefroy, Anne Gallois, Olivier Manches, Francine Jotereau, Nina Bhardwaj
Journal: Journal of Clinical Oncology (2012)

2570 Background: Cancer cells, including melanoma, can be highly resistant to traditional treatments such as chemotherapy and radiotherapy. As a result, a lot of effort has been put into developing immune therapies to treat cancer patients. The main barrier to design effective immunotherapies is the immunosuppression induced by the tumor. Matrix metalloproteinase-2 (MMP-2) is over-expressed in most cancers including melanoma, and its expression is associated with increased dissemination and poorer survival/prognosis. Here, we uncovered an immunosuppressive role of MMP-2 in inducing ineffective/detrimental T H 2 immune responses and its underlying mechanisms. Methods: Human dendritic cells (DCs) were cultured in the presence of MMP-2 or various TLR agonists. DCs responses were monitored using immunostaining, ELISA or cytometric bead array methods. Autologous CD4+ T cells were stimulated using these conditioned tumor-associated antigen (TAA)-pulsed DCs. TAA-specific CD4+ T cells were cloned and characterized using the same techniques as for DCs. Results: Herewe showed that MMP-2-conditioned human DCs primed naïve CD4+ T cells into an inflammatory T H 2 phenotype, i.e. mainly secreting TNFα, IL-4 and IL-13 and expressing GATA3. Accordingly, we detected MMP-2-specific CD4+ T cells displaying the same inflammatory T H 2 profile in tumor-infiltrating lymphocytes from melanoma patients. We revealed the underlying mechanisms: on the one hand, MMP-2 was found to degrade the type-I IFN receptor IFNAR1, thereby preventing STAT1 phosphorylation, which is necessary for IL-12 production. On the other hand, MMP-2 triggers the Toll-like receptor (TLR)-2 on DCs, which leads to NF-kB activation and OX40L expression. Both lack of IL-12 and over-expression of OX40L were found responsible for skewing T cell responses towards a detrimental T H 2 phenotype. Conclusions: MMP-2, therefore, acts as an endogenous T H 2 "conditioner" and may underlie the prevalence of detrimental T H 2 responses in cancer. Our findings also described the responsible MMP-2-dependent mechanisms, which open the way to novel therapeutic strategies and/or targets to skew anti-tumor CD4+ T cell responses towards a more efficient anti-tumor T H 1 phenotype to treat cancer patients.
The therapeutic effects of vitamin C on lung cancer cells.
Authors: Ashorne Krithiesh Mahenthiran, Gurusingham Sitta Sittampalam, Raj Somasundaram, Sanjit Nirmalanandhan
Journal: Journal of Clinical Oncology (2013)

e18523 Background: In this in-vitro study, we determined the effects of vitamin C (Ascorbic acid), an essential vitamin, on two different lung cancer cell lines (H358 – Bronchioalveolar Carcinoma and A549 – Epithelial Lung carcinoma) and two normal lung cell lines as control groups (MRC5 – Human lung fibroblast tissue and NL20 – Lung epithelial cells). Methods: In the study, the four cell lines were treated with Vitamin C starting from 0.005 molar concentrations and serially diluted down 1:3 ratios to low nM concentrations. All experiments were carried out in a period of 4 weeks. The viability of the cell lines after the drug treatment was measured using a MTS cell proliferation assay. Results: The study was inconclusive since the viability of both normal and lung cells were equally affected under the experimental conditions except that the dosage of vitamin C that killed 50% of H358 was at a slightly lower concentration than the dosage of vitamin C that killed 50% of the normal lung cells. These results show that there is a possibility of an optimal dosage that will only harm cancerous cells in specific cancers and not on all cancers. Conclusions: These results were inconclusive; probably due to the fact that experimental conditions in this in-vitro study may not be appropriate to show the effects of Vitamin C on lung cancer cells. It is possible that lower dosages of vitamin C may still kill cancer cells selectively, and may also be more effective in cancers in ther tissues. Despite these drawbacks, in-vivo experiments in animal models with lung cancer may show the benefits of Vitamin C in combination with standard of care cancer drugs. Future experiments will examine combinations experiments in vitro and in animals to study the beneficial effects of Vitamin C.
Evaluation of UGT1A1 genotyping for predicting individual toxicity of irinotecan plus platinum analog regimens: Interim safety analysis of a prospective observational study.
Authors: Masashi Takano, Kaichiro Yamamoto, Tsutomu Tabata, Yuji Minegishi, Takuma Yokoyama, Eiji Hirata, Takeshi Ikeda, Junzo Kigawa, Kouzo Yamada, Satoshi Morita, Yuichi Ando, Yukihiro Okutani, Masahiro Sugihara, Toru Sugiyama, Yasuo Ohashi, Yuh Sakata
Journal: Journal of Clinical Oncology (2013)

11049 Background: Irinotecan (IRI)+platinum (Pt) therapy works synergistically and is widely used for solid carcinomas. Although UGT1A1 genotyping has been implemented in daily practice since long, recommended doses of IRI+Pt therapy according to UGT1A1 genotyping remain undetermined. Risk factors for severe toxicities of IRI+Pt regimens remain uncertain. We conducted a prospective observational study to examine the correlation between UGT1A1 genotyping and toxicity/efficacy in IRI+Pt regimens (NCT 01040312). Methods: During October 2009 and March 2012, 321 patients were enrolled. Eligible patients had histologically confirmed SCLC, non-SCLC, cervical, ovarian, or gastric cancer; had PS 0-2; and were receiving IRI+Pt (cisplatin, carboplatin, and nedaplatin) regimen, following UGT1A1 genotyping: hetero (*1/*6, *1/*28) and homo (*6/*6, *6/*28, *28/*28). Primary endpoint was to evaluate overall toxicity profile during first 3 cycles of treatment. In this interim analysis, incidences of grade 3/4 toxicities were compared among UGT1A1 phenotypes, and logistic regression models were used to identify independent risk factors for these toxicities. Results: At the time of abstract writing, toxicity data from 137 patients were available. There were 110 (80%) hetero and 27 (20%) homo genotypes. Combination therapy of IRI (57.2 ± 12.2 mg/m 2 for average initial dose) and Pt analogs (cisplatin, 63%; carboplatin, 20%; nedaplatin, 17%) was administered. Incidences of grade 3/4 toxicities during first 3 cycles of treatment in hetero and homo were as follows: leukocytopenia, 38% and 59%; neutropenia, 55% and 67%; thrombocytopenia, 7% and 22%; and diarrhea, 9% and 7%. Overall grade 3/4 hematological toxicity was 50% (55/110) in hetero and 78% (21/27) in homo; the adjusted odds ratio was 3.379 (p = 0.0185) in homo compared with hetero. Conclusions: A higher rate of grade 3/4 hematological toxicity in homo than in hetero was confirmed with IRI+Pt therapy. Thus, UGT1A1 genotyping could be a potential biomarker of toxicity with individualized chemotherapy using low-dose IRI regimens. At the presentation, analysis of &gt;250 patients’ data will be shown. Clinical trial information: NCT01040312.
Case 8-2020: An 89-Year-Old Man with Recurrent Abdominal Pain and Bloody Stools
Authors: Hacho B. Bohossian, Emily W. Lopes, Lauren A. Roller, Ashwin N. Ananthakrishnan, Lawrence R. Zukerberg
Journal: New England Journal of Medicine (2020)

An 89-year-old man was evaluated for recurrent abdominal pain and bloody stools. During the previous 4 months, he had been hospitalized three times for the same symptoms. Diverticulosis and Clostridioides difficile colitis had been diagnosed, but despite treatment, symptoms persisted. After a fourth admission, a diagnosis was made.
Noninferiority Trials to Evaluate Drug Effects in Rheumatoid Arthritis
Authors: Rebecca Rothwell, Nikolay P. Nikolov, Janet W. Maynard, Gregory Levin
Journal: Arthritis & Rheumatology (2020)

The increased availability of highly effective treatments in rheumatoid arthritis (RA) necessitates a reexamination of study designs evaluating new treatments. We undertook this study to discuss possible specifications and considerations of noninferiority (NI) trials assessing drug effects in RA.We focused on the use of approved tumor necrosis factor inhibitors (TNFi) as potential active controls and reviewed previous placebo-controlled studies. We summarized the similarities in baseline characteristics and study design of the historical placebo-controlled studies used. After performing meta-analyses to estimate the effects of TNFi on symptoms, physical function, and radiographic progression in RA, we proposed NI margins and evaluated the feasibility of NI trials in this therapeutic setting.We determined that an NI trial comparing an experimental treatment to a TNFi using the symptomatic end point of the American College of Rheumatology 20% improvement criteria response can feasibly provide evidence of a treatment effect, with a 12% absolute difference as one possible appropriate NI margin. For change from baseline in the Health Assessment Questionnaire disability index score, reasonable margins range from 0.10 to 0.12. In evaluating radiographic progression, an appropriate margin and the corresponding feasibility of the trial are dependent on the selected active control and the expected variability in progression.Active-controlled studies in RA with justified NI margins can provide persuasive evidence of treatment effects on symptomatic, functional, and radiographic end points. Such studies can also provide reliable, controlled safety data and relevant information for treatment decisions in clinical practice. Thus, we recommend considering NI designs in future clinical trials in RA.
Surgical interventions for focal progression of gastrointestinal stromal tumors under imatinib therapy
Authors: T. Nishida, J. Hasegawa, A. Nishitani, T. Takahashi, T. Kanda, K. Hatakeyama
Journal: Journal of Clinical Oncology (2006)

9548 Background: Although Imatinib has shown high activity oin advanced gastrointestinal stromal tumors (GIST), secondary resistance appears as focal or systemic progressions during chronic therapy. At present, there are limited therapeutic options for Imatinib-resistant GIST. This retrospective study examines the safety and short-term outcomes of surgical interventions for focal progressions under Imatinib. Patients and Methods: Between Jan. 2002 and May 2005, 16 patients (pts) with focal progressions of secondarily-resistant GIST (Male:Female, 12:4; median age, 61 years) underwent surgical interventions including resection (N=13), radiofrequency ablation (RFA) (n=2), and their combination (n=1). Doses of Imatinib were 400 (n=10) or 600 (n=6) mg/day. Results: Postoperative complications including liver abscess (n=1), minor bile leak (n=1), wound infection (n=1) and transient ileus (n=1) were occurred to 4 patients, who recovered from them within a few weeks. There was no in-hospital deaths. Median time to progression (TTP) was 5.5 months. Only one patient died of the of disease, 16 months after the resection, and the remaining 15 pts are alive, with a median follow-up of 13 months. Pts with total eradication of resistant lesions (n=7) had longer TTP than those with incomplete (n=9) (p&lt;0.05). Total eradication could be performed in patients with a smaller number (P=0.014) and size (P=0.018) of resistant lesions. Overall survival after Imatinib therapy was 100% at 1 year and 93% at 3 years, with a median follow-up of 39 months. Conclusions: These data suggest that surgical interventions for focal progressions of secondarily-resistant GIST under Imatinib may be safe and that total eradication of resistant lesions may result in a survival benefits under conditions of limited treatment modality. No significant financial relationships to disclose.