tbuckley/cabot-search huggingface dataset:
Clinical effect on uncontrolled asthma using a novel digital automated self-management solution: a physician-blinded randomised controlled crossover trial
Authors: Henrik Ljungberg, Anna Carleborg, Hilmar Gerber, Christina Öfverström, Jakob Wolodarski, Faiza Menshi, Mikaela Engdahl, Marianne Eduards, Björn Nordlund
Journal: European Respiratory Journal (2019)

Introduction AsthmaTuner is a novel self-management system consisting of a patient app, a cloud-based storage solution and a healthcare interface. Patients use Bluetooth spirometers to measure lung function (forced expiratory volume in 1 s) and can register symptoms. They then receive immediate feedback on asthma control and an image of the correct inhaler(s) to use and the dose. The aim of this pilot study was to evaluate the effect of AsthmaTuner on symptom control and adherence compared with conventional treatment. Material and methods This multicentre physician-blinded crossover trial randomised patients in two groups that started with 8 weeks of AsthmaTuner or conventional treatment using a personalised printed treatment plan, with 2 weeks of washout between the crossover treatments. Participants in a primary or paediatric care setting in Sweden with asthma diagnosis, uncontrolled symptoms and Asthma Control Test (ACT) score &lt;20 points were included. Symptom control was analysed using t-tests for the difference between the group means of the sums of ACT scores at each treatment end-visit, with 95% confidence intervals. Medical Adherence Report Scale (MARS) scores captured differences in adherence (remembering to take asthma medication) between treatment periods. Results The study population consisted of 77 patients (60% females). The ACT score significantly improved with AsthmaTuner compared with conventional treatment (mean ACT difference 0.70, 95% CI 0.06–1.34; p=0.03). Adherence did not improve significantly in all participants, but did improve among those in primary care who used AsthmaTuner an average of once a week or more compared with conventional treatment (mean MARS difference 0.45, 95% CI 0.13–0.77; p=0.01). Conclusions AsthmaTuner improved symptom control in patients with uncontrolled asthma compared with conventional treatment.
Five-Year Outcomes of a Randomized Trial of Treatments for Varicose Veins
Authors: Julie Brittenden, David Cooper, Maria Dimitrova, Graham Scotland, Seonaidh C. Cotton, Andrew Elders, Graeme MacLennan, Craig R. Ramsay, John Norrie, Jennifer M. Burr, Bruce Campbell, Paul Bachoo, Ian Chetter, Michael Gough, Jonothan Earnshaw, Tim Lees, Julian Scott, Sara A. Baker, Emma Tassie, Jill Francis, Marion K. Campbell
Journal: New England Journal of Medicine (2019)

Endovenous laser ablation and ultrasound-guided foam sclerotherapy are recommended alternatives to surgery for the treatment of primary varicose veins, but their long-term comparative effectiveness remains uncertain.In a randomized, controlled trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of laser ablation, foam sclerotherapy, and surgery. Primary outcomes at 5 years were disease-specific quality of life and generic quality of life, as well as cost-effectiveness based on models of expected costs and quality-adjusted life-years (QALYs) gained that used data on participants' treatment costs and scores on the EuroQol EQ-5D questionnaire.Quality-of-life questionnaires were completed by 595 (75%) of the 798 trial participants. After adjustment for baseline scores and other covariates, scores on the Aberdeen Varicose Vein Questionnaire (on which scores range from 0 to 100, with lower scores indicating a better quality of life) were lower among patients who underwent laser ablation or surgery than among those who underwent foam sclerotherapy (effect size [adjusted differences between groups] for laser ablation vs. foam sclerotherapy, -2.86; 95% confidence interval [CI], -4.49 to -1.22; P<0.001; and for surgery vs. foam sclerotherapy, -2.60; 95% CI, -3.99 to -1.22; P<0.001). Generic quality-of-life measures did not differ among treatment groups. At a threshold willingness-to-pay ratio of £20,000 ($28,433 in U.S. dollars) per QALY, 77.2% of the cost-effectiveness model iterations favored laser ablation. In a two-way comparison between foam sclerotherapy and surgery, 54.5% of the model iterations favored surgery.In a randomized trial of treatments for varicose veins, disease-specific quality of life 5 years after treatment was better after laser ablation or surgery than after foam sclerotherapy. The majority of the probabilistic cost-effectiveness model iterations favored laser ablation at a willingness-to-pay ratio of £20,000 ($28,433) per QALY. (Funded by the National Institute for Health Research; CLASS Current Controlled Trials number, ISRCTN51995477.).
Osteonecrosis of the jaw in patients with cancer receiving zoledronic acid for bone metastases: SWOG S0702, NCT00874211.
Authors: Catherine H. Van Poznak, Joseph M. Unger, Amy K. Darke, Carol Moinpour, Robert A. Bagramian, Mark M. Schubert, Lisa Kathryn Hansen, Justin D. Floyd, Shaker R. Dakhil, Danika L. Lew, James Lloyd Wade, Michael Jordan Fisch, Norah Lynn Henry, Dawn L. Hershman, Julie Gralow
Journal: Journal of Clinical Oncology (2019)

11502 Background: Osteonecrosis of the jaw (ONJ) may occur in cancer patients (pts) with metastatic bone disease (MBD) treated with bone modifying agents. No large prospective studies have precisely determined the incidence of ONJ. A better understanding of the true incidence and predictors of ONJ is needed. Methods: SWOG S0702 was a prospective observational study that assessed the cumulative incidence (CI) of ONJ at 3 years in pts with MBD from any malignancy receiving zoledronic acid (Zol). Participants must have had either limited or no prior exposure to bone modifying agents and a clinical care plan that included use of Zol within 30 days of registration. Cancer treatments, bone modifying agents (including Zol), and dental care were administered as clinically indicated and were not directed by S0702. Baseline and every 6 m followup dental exams were recommended. Report forms (medical, dental and pt reported outcomes) were submitted every 6 m but if ONJ was diagnosed, follow up interval became every 3 m. Protocol defined ONJ required exposed bone in the maxillofacial region present 8 weeks or more in a pt who was receiving or had been exposed to a bisphosphonate, and had not had radiation therapy to the craniofacial region. Results: The study enrolled 3,491 evaluable pts (breast 1,120; myeloma 580; prostate 702, lung 666, other 423) between 2009-2013. About 2/3 of pts had a baseline dental exam. Overall, 87 pts had confirmed ONJ. The cumulative incidence of ONJ was 0.8% at year 1 (95% CI: 0.5%-1.1%), 2.0% at year 2 (95% CI: 1.5%-2.5%), and 2.8% at year 3 (95% CI: 2.3-3.5%). Rates of 3-year confirmed ONJ were highest in myeloma pts (4.3%; 95% CI, 2.8%-6.4%). Pts with planned Zol dosing intervals of every 3-4 weeks (n = 3,032, 87.2%) were much more likely to experience ONJ than pts with planned dosing intervals of 5 weeks or greater (n = 447, 12.8%; 3.2% vs 0.7%; HR = 4.80, 95% CI, 1.52-15.18, p = .008). Fewer total number of teeth, the presence of dentures and any oral surgery at baseline were all associated with a higher rate of ONJ. Conclusions: About 1 in 40 patients receiving Zol for MBD developed ONJ. S0702 provides information to guide stratification of risk for developing ONJ in pts with MBD receiving Zol. Cancer type, oral health and frequency of Zol dosing affect risk of ONJ. Clinical trial information: NCT00874211.
P03.02 Risk of leptomeningeal dissemination in patients treated with postoperative stereotactic radiotherapy of brain metastases
Authors: A Mousli, B Bihin, T Gustin, G Koerts, M Mouchamps, J F Daisne
Journal: Neuro-Oncology (2019)

Abstract Background There is a body of evidence that the risk of leptomeningeal dissemination (LMD) is increased in the postoperative stereotactic radiotherapy (SRT) of brain metastases (BM) compared to adjuvant whole brain radiotherapy (WBRT). The proposed mechanism is an iatrogenic tumor dissemination into the cerebrospinal fluid at time of surgery. Including a wider volume of meningeal wall and the entire surgical track in the definition of the postoperative SRT clinical target volume (CTV) to decrease LMD is still controversial. The aim of this study was to retrospectively analyze the outcome of adjuvant SRT targeted at resection cavities of BM without previous WBRT. MATERIAL / METHODS We reviewed 70 patients treated with postoperative SRT for BM. Stereotactic planning computed tomography and planning MRI were imported into iPlan RT image software for image registration and TV delineation. The CTV consisted of any residual enhancement and all resected cavity including a safety margin of 1 to 2 mm. Only in cases of superficial initial tumor with meningeal contact was the CTV enlarged to the adjacent meningeal wall, but never included edema or the entire surgical track. Patients underwent regular follow-up MRI. The cumulative incidence rates of LMD was retrospectively calculated as well as patterns of failure. RESULTS The most common histological type was non small cell lung cancer in 61.4%. There were 38.6% infratentorial locations and 37.2 % superficial lesions. En bloc resection was achieved in 60% and compete resection in 75.7%. After a median imaging follow up time of 16.7 months, 54.3% of patients experienced distant brain failure. LMD occurred in 9 of 70 patients (12.9 %) at a median time of 10.7 months. Survival without LMD was 88% at 1 year (IC 95% 79%-97%) and 82% at 2years (IC 95% 72%-94%). In three quarter of cases, LMD interested superficial lesions. In univariate analysis, survival rates without LMD at 1 year for superficial and deep lesions were 88 % and 94 %, respectively (p=0.49). We report only one recurrence in the surgical track (1.42%). CONCLUSION The risk of LMD was comparable to the literature (11–17%). Superficial lesions were slightly more likely to relapse in the meninges, but it was non-significant. The risk of recurrence in the surgical track is negligible. Our results do not support the current guidelines recommending the systematic inclusion of the surgical track and the related meninges in the CTV.
OS7.3 Health-related quality of life (HRQoL) evaluation in the REGOMA trial: a randomized, phase II clinical trial analyzing regorafenib activity in relapsed glioblastoma patients
Authors: G Lombardi, P Del Bianco, A Brandes, M Eoli, R Rudà, T Ibrahim, I Lolli, A Pace, B Daniele, F Pasqualetti, S Rizzato, E Bergo, M Caccese, M Padovan, R Soffietti, G De Salvo, V Zagonel
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND REGOMA trial showed that regorafenib (REG) significantly improved OS and PFS in patients (pts) with relapsed GBM with respect to lomustine (LOM). REG showed a different toxicity profile compared to LOM. Here, we report final results of the HRQoL assessment, a secondary end point. MATERIAL AND METHODS HRQoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30) and brain module (QLQ-BN20) administered before any MRI assessments, every 8 weeks (+/- 2 weeks) until disease progression. To evaluate treatment impact on HRQoL, questionnaires at progression were excluded. Mixed-effect linear models were fitted for each of the HRQOL domain to examine the change over progression-free time within and between arms. The models included the time of questionnaire assessment, the treatment group and their interaction, as fixed effects, and a compound symmetry covariance structure for the random effects. Differences of at least 10 points were classified as a clinically meaningful change. To correct for multiple comparisons and to avoid type I error, the level of significance was set at P=0.01 (2-sided). RESULTS Of 119 randomized pts, 117 partecipated in the HRQoL evaluation, and 114 had a baseline assessment (n=56 REG; n=58 LOM). No statistically significant differences were observed in any generic or cancer specific domain during treatment in the REG and LOM arms, or between the two arms, except for the appetite loss scale which was significantly worse in PTS treated with REG (Global mean 14.7 (SD=28.6) vs 7.6 (SD=16.0); p=0.0081). The rate of pts with a clinically meaningful worsening for appetite loss was not statistically different between the two arms (9 out of 24 and 0 out of 13 in the REG and LOM arm, respectively;p=0.02). CONCLUSION In the REGOMA trial, HRQoL did not change during regorafenib treatment. Pts treated with regorafenib and lomustine reported no significant difference in HRQoL.
Healthcare utilization of people with AK
Authors: E.C. Noels, L.M. Hollestein, S. Egmond, M. Lugtenberg, L.P.J. Nistelrooij, P.J.E. Bindels, J. Lei, R.S. Stern, T. Nijsten, M. Wakkee
Journal: British Journal of Dermatology (2019)

Actinic keratoses (AK) are rough skin lesions (patches) caused by long-term sun exposure in people with light skin. The prevalence of AK is high, affecting 24-60% of people above the age of 50. Having many AKs is a sign that a person may be more likely to develop skin cancer. This study, from the Netherlands, aimed to provide insight in the management (treatment) of AKs, by describing how healthcare services are used by people with AK, and its management by GPs and dermatologists. The authors found that a large proportion of people with AK are not aware of having AK, and thus not aware of an increased skin cancer risk. Its treatment at the GP largely seems inconsistent with guidelines, and 31% are directly referred to the dermatologist at the first GP appointment. These referrals are usually not related to the extensiveness of the AK, meaning how many AKs the person has. This causes a high burden in secondary care (e.g. hospitals, where people are referred to dermatologists) with patients who could be easily treated by the GP. At the dermatologists there is a high rate of follow-up of patients with AK, meaning they come back for further appointments. The authors conclude that their findings indicate inefficient use of healthcare resources. They suggest that to overcome this, motives of GPs and dermatologists for diverging from current guidelines in the management of AK need to be explored.
Serine-Phosphorylated STAT3 Promotes Tumorigenesis via Modulation of RNA Polymerase Transcriptional Activity
Authors: Jesse J. Balic, Daniel J. Garama, Mohamed I. Saad, Liang Yu, Alison C. West, Alice J. West, Thaleia Livis, Prithi S. Bhathal, Daniel J. Gough, Brendan J. Jenkins
Journal: Cancer Research (2019)

Deregulated activation of the latent oncogenic transcription factor STAT3 in many human epithelial malignancies, including gastric cancer, has invariably been associated with its canonical tyrosine phosphorylation and enhanced transcriptional activity. By contrast, serine phosphorylation (pS) of STAT3 can augment its nuclear transcriptional activity and promote essential mitochondrial functions, yet the role of pS-STAT3 among epithelial cancers is ill-defined. Here, we reveal that genetic ablation of pS-STAT3 in the gp130F/F spontaneous gastric cancer mouse model and human gastric cancer cell line xenografts abrogated tumor growth that coincided with reduced proliferative potential of the tumor epithelium. Microarray gene expression profiling demonstrated that the suppressed gastric tumorigenesis in pS-STAT3-deficient gp130F/F mice associated with reduced transcriptional activity of STAT3-regulated gene networks implicated in cell proliferation and migration, inflammation, and angiogenesis, but not mitochondrial function or metabolism. Notably, the protumorigenic activity of pS-STAT3 aligned with its capacity to primarily augment RNA polymerase II-mediated transcriptional elongation, but not initiation, of STAT3 target genes. Furthermore, by using a combinatorial in vitro and in vivo proteomics approach based on the rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) assay, we identified RuvB-like AAA ATPase 1 (RUVBL1/Pontin) and enhancer of rudimentary homolog (ERH) as interacting partners of pS-STAT3 that are pivotal for its transcriptional activity on STAT3 target genes. Collectively, these findings uncover a hitherto unknown transcriptional role and obligate requirement for pS-STAT3 in gastric cancer that could be extrapolated to other STAT3-driven cancers. SIGNIFICANCE: These findings reveal a new transcriptional role and mandatory requirement for constitutive STAT3 serine phosphorylation in gastric cancer.
Apatinib for epithelioid sarcoma: analysis on eight advanced stage cases in a single institute.
Authors: Yong Chen, Wei Sun, Bing Wang, Xing-Long Qu, Bi-Qiang Zheng, Wen-Ding Huang, Zheng-Wang Sun, Chun-Meng Wang
Journal: Journal of Clinical Oncology (2019)

e22551 Background: Epithelioid sarcoma (ES) is a rare high grade soft tissue sarcoma with high incidence of lymph node involvement and distant metastasis. It is widely recognized that ES is not sensitive to chemotherapy and radiation, surgical treatment is the only curative option for localized diseases. Tyrosine kinase inhibitors (TKIs) has been proven to be effective in sarcomas, here we report the experience of Apatinib in 8 advanced ES cases. Methods: ES patients treated in Fudan University Shanghai Cancer Center from Dec, 2016 to Aug, 2018 were accrued retrospectively. Those with locally advanced diseases or distant metastasis were treated with orally Apatinib 500mg, daily use for at least 2 months. Assessment of efficacy and side effects were recorded every 2 months and patients were then treated according to reponses to Apatinib. Results: There were 8 patients with locally advanced or late stage ES in a total 20 ES patients during the study period. There were 6 males and 2 females with median age of 55 years (20-73). 3 of the 8 were classical type and 5 were proximal type. 7 of the 8 patients were locally advanced and 1 was with lung metastasis at diagnosis. 4 of the 8 had a partial response to Apatinib and one patient has a downstaged ES which was surgically removed. The other 4 had a stable disease to Apatinib but 2 were not able to tolerate side effects and stopped at first evaluation, the other 2 remains progression free. Main side effects included skin rash, hypertension and diarrhea. Hypertension was the only Grade 3-4 side effect. With median follow-up of 12 months, 6 remains progression free, the 2 patients who didn’t tolerate side effects and stopped Apatinib developed lung metastasis. Conclusions: Apatinib has unproven but promising effect in ES, TKI is an option especially for those not sensitive to cytotoxic agents and radiation.
Association of Blood Marker of Inflammation in Late Adolescence With Premature Mortality
Authors: Elizabeth D. Kantor, Ruzan Udumyan, Edward L. Giovannucci, Unnur A. Valdimarsdottir, Lisa B. Signorello, Scott Montgomery, Katja Fall
Journal: JAMA Pediatrics (2019)

This study evaluates the association of inflammation in late adolescence as measured by erythrocyte sedimentation rate with cause-specific mortality among healthy Swedish men assessed for conscription in the military.
P14.48 Identification of subsets of IDH-mutant glioblastomas with distinct epigenetic and copynumber alterations and stratified clinical risks
Authors: A K CHAN, K K Li, Z F Shi, H K Ng
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND IDH-mutant glioblastoma is classified by the 2016 CNS WHO as a group with good prognosis. However, the actual number of cases examined in the literature is relatively small. We hypothesize that IDH-mutant glioblastoma is not a uniform group and should be further stratified. MATERIAL AND METHODS We conducted methylation profiles and estimated copy number variations in 64 IDH-mutant glioblastomas. RESULTS Our results showed that 10.9%, 53.1%, and 35.9% of tumors belonged to Codel, G-CIMPhigh, and G-CIMP-low methylation subgroups, respectively. G-CIMP-low subgroup was associated with significantly worse OS as compared to G-CIMP-high (P=0.005) and Codel groups (P=0.009). CDKN2A deletion (37.5%) was the most common gene copy number variation, and was associated with G-CIMP-low subgroup (P=0.001). Other frequent copy number changes included MET (4.7%), CCND2 (17.2%), PDGFRA (14.1%), CDK4 (12.5%), and EGFR (12.5%) amplification. Both CDKN2A deletion (P=0.008) and MET amplification (P&lt;0.001) were associated with poor OS in IDH-mutant glioblastomas. Combined epigenetic signatures and gene copy number variations separated IDH-mutant glioblastomas into Group 1 (Codel), Group 2 (GCIMP- high), Group 3 (G-CIMP-low without CDKN2A and MET alterations), and Group 4 (G-CIMP-low with CDKN2A/MET alteration). Survival analysis revealed Group 1 had a favorable OS (median survival: 41.3 months), while Groups 2 and 3 exhibited an intermediate OS (median survival: 20.6 and 21.8 months, respectively). Group 4 exhibited the worst OS (median survival: 8.4 months). Multivariable analysis confirmed the independent prognostic significance of our Groups. CONCLUSION IDH-mutant glioblastomas should be stratified for risk with combined epigenetic signature and CDKN2A/MET status and some cases have poor outcome.
Small Bowel Adenocarcinoma: Etiology, Presentation, and Molecular Alterations
Authors: Katrina S. Pedersen, Kanwal Raghav, Michael J. Overman
Journal: Journal of the National Comprehensive Cancer Network (2019)

Small bowel adenocarcinoma (SBA) is a rare cancer that has been treated similarly to colorectal cancer (CRC) in the advanced setting. Incidence has been increasing as detection efforts have been improving for these challenging-to-diagnose tumors, but patients frequently experience prolonged nonspecific symptoms due to delayed diagnosis. As a result of such delays and likely due to variant biology, patient outcomes for SBA are inferior to those for CRC at all stages of diagnosis. Recent molecular studies highlight the genomic differences underpinning these tumors and suggest new future pathways for treatment, distinct from CRC.
Loss-of-function variants in myocardin cause congenital megabladder in humans and mice
Authors: Arjan C. Houweling, Glenda M. Beaman, Alex V. Postma, T. Blair Gainous, Klaske D. Lichtenbelt, Francesco Brancati, Filipa M. Lopes, Ingeborg van der Made, Abeltje M. Polstra, Michael L. Robinson, Kevin D. Wright, Jamie M. Ellingford, Ashley R. Jackson, Eline Overwater, Rita Genesio, Silvio Romano, Letizia Camerota, Emanuela D’Angelo, Elizabeth J. Meijers-Heijboer, Vincent M. Christoffels, Kirk M. McHugh, Brian L. Black, William G. Newman, Adrian S. Woolf, Esther E. Creemers
Journal: Journal of Clinical Investigation (2019)

Myocardin (MYOCD) is the founding member of a class of transcriptional coactivators that bind the serum-response factor to activate gene expression programs critical in smooth muscle (SM) and cardiac muscle development. Insights into the molecular functions of MYOCD have been obtained from cell culture studies, and to date, knowledge about in vivo roles of MYOCD comes exclusively from experimental animals. Here, we defined an often lethal congenital human disease associated with inheritance of pathogenic MYOCD variants. This disease manifested as a massively dilated urinary bladder, or megabladder, with disrupted SM in its wall. We provided evidence that monoallelic loss-of-function variants in MYOCD caused congenital megabladder in males only, whereas biallelic variants were associated with disease in both sexes, with a phenotype additionally involving the cardiovascular system. These results were supported by cosegregation of MYOCD variants with the phenotype in 4 unrelated families by in vitro transactivation studies in which pathogenic variants resulted in abrogated SM gene expression and by the finding of megabladder in 2 distinct mouse models with reduced Myocd activity. In conclusion, we have demonstrated that variants in MYOCD result in human disease, and the collective findings highlight a vital role for MYOCD in mammalian organogenesis.