tbuckley/cabot-search huggingface dataset:
Cardiometabolic Risk Factor Changes Observed in Diabetes Prevention Programs in US Settings: A Systematic Review and Meta-analysis
Authors: Uma Mudaliar, Azadeh Zabetian, Michael Goodman, Justin B. Echouffo-Tcheugui, Ann L. Albright, Edward W. Gregg, Mohammed K. Ali
Journal: PLoS Medicine (2016)

The Diabetes Prevention Program (DPP) study showed that weight loss in high-risk adults lowered diabetes incidence and cardiovascular disease risk. No prior analyses have aggregated weight and cardiometabolic risk factor changes observed in studies implementing DPP interventions in nonresearch settings in the United States.In this systematic review and meta-analysis, we pooled data from studies in the United States implementing DPP lifestyle modification programs (focused on modest [5%-7%] weight loss through ≥150 min of moderate physical activity per week and restriction of fat intake) in clinical, community, and online settings. We reported aggregated pre- and post-intervention weight and cardiometabolic risk factor changes (fasting blood glucose [FBG], glycosylated hemoglobin [HbA1c], systolic or diastolic blood pressure [SBP/DBP], total [TC] or HDL-cholesterol). We searched the MEDLINE, EMBASE, Cochrane Library, and Clinicaltrials.gov databases from January 1, 2003, to May 1, 2016. Two reviewers independently evaluated article eligibility and extracted data on study designs, populations enrolled, intervention program characteristics (duration, number of core and maintenance sessions), and outcomes. We used a random effects model to calculate summary estimates for each outcome and associated 95% confidence intervals (CI). To examine sources of heterogeneity, results were stratified according to the presence of maintenance sessions, risk level of participants (prediabetes or other), and intervention delivery personnel (lay or professional). Forty-four studies that enrolled 8,995 participants met eligibility criteria. Participants had an average age of 50.8 years and body mass index (BMI) of 34.8 kg/m2, and 25.2% were male. On average, study follow-up was 9.3 mo (median 12.0) with a range of 1.5 to 36 months; programs offered a mean of 12.6 sessions, with mean participant attendance of 11.0 core sessions. Sixty percent of programs offered some form of post-core maintenance (either email or in person). Mean absolute changes observed were: weight -3.77 kg (95% CI: -4.55; -2.99), HbA1c -0.21% (-0.29; -0.13), FBG -2.40 mg/dL (-3.59; -1.21), SBP -4.29 mmHg (-5.73, -2.84), DBP -2.56 mmHg (-3.40, 1.71), HDL +0.85 mg/dL (-0.10, 1.60), and TC -5.34 mg/dL (-9.72, -0.97). Programs with a maintenance component achieved greater reductions in weight (additional -1.66kg) and FBG (additional -3.14 mg/dl). Findings are subject to incomplete reporting and heterogeneity of studies included, and confounding because most included studies used pre-post study designs.DPP lifestyle modification programs achieved clinically meaningful weight and cardiometabolic health improvements. Together, these data suggest that additional value is gained from these programs, reinforcing that they are likely very cost-effective.
Authors’ reply to Divers and Braillon
Authors: Michael Kinney, James Morrow
Journal: BMJ (2016)

We thank Divers and Braillon for their comments on our article,1 which sought to raise awareness about epilepsy management in pregnancy.2 3

Divers correctly highlights that it is current practice to supplement vitamin K in infants born to women using enzyme inducing antiepileptic drugs (AEDs), a point not covered in our paper. This is mentioned in various guidelines, but the evidence …
Clinical Improvement with JAK2 Inhibition in Chuvash Polycythemia
Authors: Amy W Zhou, Eric M Knoche, Elizabeth K Engle, Makiko Ban-Hoefen, Charu Kaiwar, Stephen T Oh
Journal: New England Journal of Medicine (2016)

Rare mutations in the VHL gene may lead to polycythemia in children. Ruxolitinib resulted in clinical improvement in three people with this disorder.
Ofatumumab monotherapy as a consolidation strategy in patients with previously untreated chronic lymphocytic leukaemia: a phase 2 trial
Authors: Paolo Strati, Mark Lanasa, Timothy G Call, Jose F Leis, Danielle M Brander, Betsy R LaPlant, Adam M Pettinger, Wei Ding, Sameer A Parikh, Curtis A Hanson, Asher A Chanan-Khan, Deborah A Bowen, Michael Conte, Neil E Kay, Tait D Shanafelt
Journal: The Lancet Haematology (2016)
Topical calcitriol (BPM31543) for the prevention of chemotherapy-induced alopecia (CIA): Efficacy findings from a phase I safety study.
Authors: Mario E. Lacouture, Jason A. Konner, Janice Stevens, Susan Brouwer, Niven R. Narain, Ran Ye, Shobha Ravipaty, Rangaprasad Sarangarajan, Viacheslav R Akmaev, Joaquin Juan Jimenez, Viswanath Reddy Belum, Sarah Kitts, Kathryn Ciccolini, Brian Berman, Shari Beth Goldfarb
Journal: Journal of Clinical Oncology (2016)

2564 Background: Cancer patients receiving taxane-based chemotherapy develop alopecia, which may lead to significant psychosocial, quality of life, and adherence issues. Besides a recently FDA-cleared scalp cooling device, there are no oral/ topical agents available prevent CIA. In murine studies, topical calcitriol reduced CIA, likely due to arrest of cell cycle in healthy hair follicles, and reduction in the sensitivity of follicular epithelium to chemotherapy. Methods: Up to 31 adult women with cancer (breast, gynecologic, soft-tissue/bone sarcoma) applied 1mL of BPM31543 to scalp bid, ≥ 5 days prior to initiation of taxane-based chemotherapy until 3 months or end of chemotherapy, in this dose-escalation study (5/10/20/40/60/80μg/mL cohorts). Periodic PK analysis, adverse event (AE) monitoring, patient self-assessment diaries (1-10 scale), and blinded photographic assessments were done. Results: Twenty-one subjects have been enrolled so far (evaluable, n = 13). PK data (n = 16; 5-40μg/mL) showed inter-individual variability, but no significant dose-dependent increase in systemic absorption (range, < 20-110 pg/mL). Treatment-related AEs (probably/possibly) were mild/moderate, and included scalp pain (n = 1; 5 μg/mL), elevated vitamin D levels in 1 patient (20μg/mL) and with passage of renal calculus in another (n = 1; 40μg/mL). All subjects reported changes in overall fullness, thickness, and volume of hair during chemotherapy, and experienced hair loss, with 85% showing a ≥ 75% increase in their rating (maximum, week 4) at the 5/10 μg/mL dose level. At the ≥ 20 μg/mL dose level, ≥ 75% hair loss was seen only in 43%. Hair loss/ thinning caused all subjects to change their hair style (onset, week 2; peak, weeks 5-6). Conclusions: Topical BPM31543 is safe and tolerable with potential activity at higher dosing levels. Clinical trial information: NCT01588522.Prevention of CIA with Topical Calcitriol: blinded photographic assessment of hair loss (7 sites). Maximal hair loss at any scalp site (Week 7 assessment vs. Baseline) Dose level (µg/mL), n = 12 5 10 20 40 -3 [Greatly decreased, > 75%] #009 #018, #019 -2 [Moderately decreased, 50-75%] #001 #007 #010 -1 [Slightly decreased, 25-49%] #002, #003 #004 #012, #014 #016
Reporting of endpoints and tracking of failures in randomized trials of radiotherapy or concurrent chemoradiotherapy for locally advanced head and neck squamous cell cancer (LA-HNSCC)
Authors: C. Le Tourneau, S. Michiels, H. Gan, L. Siu
Journal: Journal of Clinical Oncology (2009)

6072 Background: Due to their anatomical complexity, the interactive effects of multiple treatment modalities, the difficulties in differentiating scar tissues versus residual disease and second cancers versus tumor recurrence, LA-HNSCC represent a challenging disease for the reporting of endpoints and the tracking of failures. Methods: We retrieved all randomized trials that began accrual on or after 1978, and enrolled previously untreated nonmetastatic HNSCC patients receiving primary (chemo)radiotherapy. The reporting of endpoints and the tracking of failures in these trials were analyzed. Failures were defined as events meeting a pre-specified endpoint definition. Results: Forty trials involving 13,892 patients fulfilled our inclusion criteria. A total of 125 endpoints were identified: primary versus secondary = 34:91, survival-based (e.g., overall survival [OS]) versus surrogate (e.g. locoregional control [LRC]) = 47:78. In 6 trials, no primary endpoint was identified. LRC and OS accounted for 70% of primary endpoints. All but one trial reported at least one secondary endpoint, with a median of 2 per trial (range: 0–5), and as many as 17 different types of secondary endpoints were reported. Among 72 endpoints tracking locoregional failures, 21/72 (29%) did not define locoregional failure, while 46/72 (64%) specified the absence of complete response as a failure. Whether salvage surgery or elective node dissection was performed or not was reported in less than half of the trials. Furthermore, it was usually not specified if residual disease found during these procedures would account for failure or not. The means (i.e. clinical and/or radiological examinations) to ascertain failures and the protocol-specified timing to track failures were reported in 41% and 67% of surrogate endpoints, respectively. The tracking of other types of failure beyond the first failure is not reported by any of the trials. The reporting of second cancers was found in 15/40 (38%) trials, whereas the duration of follow-up was quantified in 31/40 (78%) trials. Conclusions: These results demonstrate the vast heterogeneity in endpoint reporting and tracking of failures in clinical trials of LA-HNSCC. No significant financial relationships to disclose.
An Important Cause of Child and Youth Homelessness—Reply
Authors: Lonnie Embleton, Paula Braitstein
Journal: JAMA Pediatrics (2016)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
Abstract 4756: N-cadherin signaling predicts prognosis in medulloblastoma subtypes
Authors: Maria Sverdlov, Michael P. Downing, Shuqi Kang, Anjen Chenn
Journal: Cancer Research (2016)

Abstract Identification of signaling pathways that drive the clinical behavior of tumors will guide specific molecular therapies. Medulloblastoma, the most common malignant pediatric solid tumor, shows considerable clinical and molecular diversity, providing impetus for specific targeted therapies of predicted molecular drivers. Here we show a gene signature derived from in vitro experimental inhibition of N-cadherin in medulloblastoma (MB) cells predicts survival in human MB in two large independent patient cohorts. Patients with high N-cadherin signature scores had earlier death and reduced overall survival. We found novel heterogeneity in proposed MB molecular subgroups, with significant differences in survival predicted by the N-cadherin signature in sonic hedgehog (SHH) and c2 tumors. In cultured MB cells, N-cadherin cell-cell interactions activated beta-catenin signaling and increased expression of the cancer stem cell regulator Sox2, known to be critical in the growth and relapse of SHH MB. Inhibition of N-cadherin reduced beta-catenin signaling and Sox2. Together, these findings indicate N-cadherin activity predicts the survival of patients with MB and suggest that differential activity of cellular pathways can identify novel disease subgroups and reveal molecular mechanisms with therapeutic significance. Citation Format: Maria Sverdlov, Michael P. Downing, Shuqi Kang, Anjen Chenn. N-cadherin signaling predicts prognosis in medulloblastoma subtypes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4756.
PET imaging with <sup>68</sup>Gallium-labelled ligand of prostate-specific membrane antigen (<sup>68</sup>Ga-HBED-PSMA) for staging of biochemical recurrent prostate cancer after radical prostatectomy.
Authors: Tobias Maurer, Juergen Gschwend, Hans-Juergen Wester, Michael Souvatzoglou, Ambros Beer, Konstantin Holzapfel, Gregor Weirich, Bernhard Haller, Hubert Kübler, Markus Schwaiger, Matthias Eiber
Journal: Journal of Clinical Oncology (2015)

5023 Background: Staging of recurrent prostate cancer (PCa) after radical prostatectomy (RP) remains challenging especially at low PSA values. Prostate-specific membrane antigen (PSMA) shows increased expression on most PCa and might therefore be useful for detection of PCa lesions. Aim of this retrospective analysis of consecutive pts was to evaluate the detection rate of PET hybrid imaging using the PSMA inhibitor Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)] (68Ga-HBED-PSMA) in pts with biochemical recurrence (BCR) of PCa after RP. Methods: 332 consecutive pts with BCR of PCa after RP and a median PSA value of 1.7 ng/ml (range 0.2-63 ng/ml) were included in this analysis. After injection of 122±17 MBq 68Ga-HBED-PSMA-PET/CT or PET/MR was performed in 256 pts and 76 pts, respectively. One nuclear medicine physician and one radiologist reviewed imaging in consensus. Detection rates according to PSA value were determined. Results: In total, detection rates for 68Ga-HBED-PSMA-PET hybrid imaging were 96.0% (143/149) for PSA values ≥ 2ng/ml, 92.0% (80/87) for PSA values 1-2ng/ml, 72.3% (34/47) for PSA values 0.5-1ng/ml and 53.0% (26/49) for PSA values 0.2–0.5ng/ml, respectively. In 28.9% (96/332) of pts solely PSMA-PET detected suspicious lesions whereas 2.7% (9/332) of pts only showed positive findings in morphological imaging. Additional lesions were seen in 21.4% (71/332) of pts in PSMA-PET and in 6.3% (21/332) in CT or MRI. Conclusions: 68Ga-HBED-PSMA-PET hybrid imaging shows higher detection rates in pts with recurrent PCa at low PSA values than reported for other PET-tracers like 18F-FDG or choline derivatives. Thus, 68Ga-HBED-PSMA-PET hybrid imaging has the potential to replace PET imaging with these tracers for staging of BCR of PCa after RP in the future.
BASCULE syndrome, orthostatic cyanosis and postural orthostatic tachycardia syndrome: time for decanting old wine?
Authors: D. Bessis, V. Pallure, É. Jeziorski
Journal: British Journal of Dermatology (2016)

We thank Dr McGibbon for his comments on the BASCULE syndrome (Bier's Anemic Spots associated with Cyanosis and Urticaria-Like Eruption).

The author suggests that this syndrome is essentially a redescription of “orthostatic acrocyanosis (OA)” associated with chronic orthostatic intolerance and postural tachycardia syndrome (POTS), as previously reported by Stewart.1 We would like to address this assertion. Although we agree that our description of BASCULE syndrome in adult patients is close to the picture that Stewart labelled “acrocyanosis in POTS”

This article is protected by copyright. All rights reserved.
Abstract 3296: Breast mammographic density and the fecal microbiota
Authors: Gieira S. Jones, Heather S. Feigelson, Jacques Ravel, James J. Goedert
Journal: Cancer Research (2016)

Abstract The microbial population (microbiota) of the distal human gut has multiple functions that modulate cancer risk including digestion of nutrients, deconjugation and enterohepatic circulation of hormones and other bile acids, and regulation of immunity and inflammation. We have previously reported that postmenopausal breast cancer cases, compared to controls, have lower fecal microbiota alpha diversity, independent of age, body mass index, and estrogen levels, and that the cases’ microbiota is compositionally altered. For deeper understanding of these associations with breast cancer, we compared microbiota metrics to a strong cancer risk factor, breast density, among 48 cancer-free, postmenopausal controls in the Breast and Colon Health study (86% non-Hispanic White, mean age 62 years). In routine screening mammograms, they had the following Breast Imaging Reporting and Data System (BI-RADS, 5th ed.) composition: a) almost entirely fatty (N = 4); b) scattered areas of fibroglandular density (N = 14); c) heterogeneously dense (N = 26); and d) extremely dense (N = 4). As shown in the Table, simple linear regression across these four ordered BI-RADS categories revealed that there was no significant association with fecal microbiota alpha diversity (PD_tree β -0.08, P = 0.56). Breast density in these women also was not associated with microbiota beta diversity (composition) by MiRKAT analysis of un-weighted and weighted UniFrac metrics (P = 0.25 and 0.08, respectively). We conclude that breast density is unlikely to mediate the association of the gut microbiota with breast cancer in postmenopausal women. Fecal alpha diversity by mammographic density categoryBI-RADS DensityNo.Mean (SD) PD_Whole_TreeAlmost Entirely Fatty436.06 (4.22)Scattered Fibroglandular1438.18 (8.25)Heterogeneously Dense2637.19 (4.88)Extremely Dense438.33 (7.99) Citation Format: Gieira S. Jones, Heather S. Feigelson, Jacques Ravel, James J. Goedert. Breast mammographic density and the fecal microbiota. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3296.
Air pollution affects lung cancer survival
Authors: Sandrah P Eckel, Myles Cockburn, Yu-Hsiang Shu, Huiyu Deng, Frederick W Lurmann, Lihua Liu, Frank D Gilliland
Journal: Thorax (2016)

<h3>Rationale</h3> Exposure to ambient air pollutants has been associated with increased lung cancer incidence and mortality, but due to the high case fatality rate, little is known about the impacts of air pollution exposures on survival after diagnosis. This study aimed to determine whether ambient air pollutant exposures are associated with the survival of patients with lung cancer. <h3>Methods</h3> Participants were 352 053 patients with newly diagnosed lung cancer during 1988–2009 in California, ascertained by the California Cancer Registry. Average residential ambient air pollutant concentrations were estimated for each participant9s follow-up period. Cox proportional hazards models were used to estimate HRs relating air pollutant exposures to all-cause mortality overall and stratified by stage (localised only, regional and distant site) and histology (squamous cell carcinoma, adenocarcinoma, small cell carcinoma, large cell carcinoma and others) at diagnosis, adjusting for potential individual and area-level confounders. <h3>Results</h3> Adjusting for histology and other potential confounders, the HRs associated with 1 SD increases in NO<sub>2</sub>, O<sub>3</sub>, PM<sub>10</sub>, PM<sub>2.5</sub> for patients with localised stage at diagnosis were 1.30 (95% CI 1.28 to 1.32), 1.04 (95% CI 1.02 to 1.05), 1.26 (95% CI 1.25 to 1.28) and 1.38 (95% CI 1.35 to 1.41), respectively. Adjusted HRs were smaller in later stages and varied by histological type within stage (p&lt;0.01, except O<sub>3</sub>). The largest associations were for patients with early-stage non-small cell cancers, particularly adenocarcinomas. <h3>Conclusions</h3> These epidemiological findings support the hypothesis that air pollution exposures after lung cancer diagnosis shorten survival. Future studies should evaluate the impacts of exposure reduction.
Abstract 4600: Regulation of Wnt/β-catenin signaling by Wnt co-receptor LRP6 in colorectal cancer cells
Authors: Yonghe Li, Wenyan Lu, Taj D. King
Journal: Cancer Research (2016)

Abstract Mutations of APC and CTNNB1 are two major factors for Wnt/β-catenin signaling over-activation in colorectal cancer, however recent studies indicate that the levels of Wnt/β-catenin signaling in colorectal cancer cells could be modulated on the cell surface. The low-density lipoprotein-related protein 6 (LRP6) is an essential Wnt co-receptor for the Wnt/β-catenin signaling pathway. Herein, we reported that LRP6 expression is up-regulated in colorectal cancer. Moreover, LRP6 silencing significantly reduced Wnt/β-catenin signaling in colorectal cancer HCT116 cells (harboring a CTNNB1 mutation) and DLD-1 cells (harboring an APC mutation) and inhibited cancer cell viability. In addition, treatment of HCT116 cells with Wnt3A resulted in LRP6 phosphorylation and activation of Wnt/β-catenin signaling, which was blocked by LRP6 antagonist Mesd. Finally, we found that salinomycin, a potent small molecule inhibitor of LRP6, suppressed LRP6 expression and phosphorylation, inhibited Wnt/β-catenin signaling in colorectal cancer HCT116 and DLD-1 cells, and repressed cancer cell viability and colony formation within the same concentration range. Together, these results indicate that LRP6 plays an important role in over-activation of Wnt/β-catenin signaling in colorectal cancer cells, and that LRP6 is a potential therapeutic target for colorectal cancer. Citation Format: Yonghe Li, Wenyan Lu, Taj D. King. Regulation of Wnt/β-catenin signaling by Wnt co-receptor LRP6 in colorectal cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4600.
Comparaison entre différents types de préparation colique dans le cadre du dépistage. Une étude de non-infériorité dans un programme de dépistage en Italie
Authors: G Lesur
Journal: Endoscopy (2016)

De nombreuses études ont déjà été consacrées aux comparaisons des différents types de préparations pour les coloscopies dans le cadre des programmes de dépistage du cancer colorectal par test immunologique.