tbuckley/cabot-search huggingface dataset:
Another Look at the Baby-Friendly Hospital Initiative
Authors: Marsha Walker
Journal: JAMA Pediatrics (2019)

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Guideline: 8 professional organizations recommend percutaneous closure of patent foramen ovale in selected patients
Authors: Dinesh Jillella, Ken Uchino
Journal: Annals of Internal Medicine (2019)

Source Citation Pristipino C, Sievert H, D’Ascenzo F, et al; Evidence Synthesis Team; Eapci Scientific Documents and Initiatives Committee; International Experts. European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism. Eur Heart J. 2018. [Epub ahead of print]. 30358849
Clinicopathologic considerations of neuroendocrine tumors (NETs) in Greece: A registry experience.
Authors: Anna Koumarianou, George Nikou, Dimitrios Dimitroulopoulos, Theodoros Angelopoulos, Michalis Papamichelakis, Stylianos Mandanas, Alexandra Chrisoulidou, Erasmia Vlachou, Georgios Alexandrakis, Pavlos Papakostas, Michael Vaslamatzis, Philippos Kaldrymidis, Apostolos Malachias, Nektarios Alevizopoulos, Panagiotis Katsaounis, Vyron Markussis, Kalliopi Pazaitou
Journal: Journal of Clinical Oncology (2015)

e15191 Background: The rarity of NETs has contributed to a paucity of large epidemiologic studies. We investigated their clinical features and therapies in Greece Methods: Between October 2010 and November 2012 we collected data on 246 newly diagnosed patients from a broad-based multi-institutional registry that comprises eight academic/hospital sites Results: The median age at diagnosis was 57 years (range 18-82), 121 (49%) were males, 94% were sporadic and 6% had multiple endocrine neoplasia. Primary sites included 64% gastroenteropancreatic (GEP) (49 gastroenteric, 15% pancreatic), 18% head & neck, 10% of unknown primary, 6% lung and 2% adrenal. Fifteen percent of patients were asymptomatic at presentation, 24% had a first symptom of the disease related to endocrine syndrome (14% flushing & 12% diarrhea) and 61% had symptoms related to locally advanced/metastatic disease (44% dyspepsia, 39% pain & 36% asthenia). Metastatic disease was seen in 25% of patients most frequently in the GEP NET group. Distribution according to pathologic grade included 59% well, 32 % moderately & 9% poorly differentiated subtypes. The majority of NETs had a Ki-67 ≤ 2 (73%). Among the imaging procedures applied for NET diagnosis MRI provided the highest positive yield (75%) followed by Octreoscan (50%). Somatostatin analog was the most frequently prescribed treatment, followed by chemotherapy, everolimus and sunitinib. Lanreotide and octreotide acetate were both prescribed and found to be equally effective at providing symptomatic relief in NET patients (see table below). During the follow-up period of the registry 10 deaths (6 gastrenteric/2 pancreatic/2 pheochromocytomas) were documented, corresponding to 4.1% of patients. Conclusions: We report the first Greek registry and one of the few European providing information on patients with NETs of various origin sites, beyond GEPNETs. Symptomatic Outcome of patients treated with Somatuline and Sandostatin (Fisher’s exact test = 0.295). SOMATULINE N, % SANDOSTATIN N, % TOTAL N, % Missing Data 5 6 11 45.5% 54.5% 100.0% Improvement 24 25 49 49.0% 51.0% 100.0% Deterioration 4 7 11 36.4% 63.6% 100.0% Stabilization 44 85 129 34.1% 65.9% 100.0% Total N 77 123 200 38.5% 61.5% 100.0%
Profile of BRCA testing in ovarian cancer patients in the United States and European Union.
Authors: Sabina Heinz, Pieter De Richter, Ayse Levent, Stella Moss, Jerzy Tyczynski
Journal: Journal of Clinical Oncology (2015)

e16565 Background: Around 13% of patients (pts) with ovarian cancer harbor mutations in the BRCA genes. Their disease has distinct characteristics which may impact treatment pathways. However, currently only a subset of ovarian cancer pts are offered testing for BRCA mutations, based largely upon family history of BRCA-related tumors. Frequencies of, and barriers to, testing are not well characterized; therefore, the objective was to describe current BRCA testing practices in relation to women diagnosed with ovarian cancer. Methods: A survey of 234 oncologists, including detailed questionnaires relating to 297 BRCA-tested ovarian cancer pts, in the US, UK, France, Germany, Italy and Spain was conducted between October and December 2014 by Ipsos Healthcare’s Syndicated MDx Monitor. A similar survey was conducted in 2013, allowing comparison over time. Results: Physician awareness of BRCA testing in ovarian cancer pts varies: 79% in 5EU and 98% in US. On average, between 26% (EU) to 40% (US) of ovarian cancer pts were tested for BRCA (excluding pre-diagnosis testing). In both regions, 76–78% of all tested pts were tested with a blood test only, with tumor testing being used significantly less. Most frequently mentioned top barriers to performing blood testing included the cost of testing (31% in US, 15% in 5EU), lack of guidelines (2% in US, 11% in 5EU) and the fact that only a subset of pts are eligible (9% in the US, 6% in 5EU). For tumor testing, test cost was also important, in addition to a perceived lack of data on clinical utility (17% in US, 12% in 5EU). Focusing on the timing of all BRCA tests that were conducted, the data showed that in the US, 79% of BRCA testing occurred prior to or at the point of diagnosis, compared with 73% in 5EU. Conclusions: While there is broad knowledge and use of BRCA testing, the survey has highlighted significant barriers which may prevent ovarian cancer pts from being offered the test. Furthermore, there is a current perceived lack of clinical utility among a significant subset of doctors when it comes to tumor testing, leading to much lower rates compared with blood testing.
Abstract P419: Migraine and Arterial Stiffness in the Brazilian Longitudinal Study of Adult Health ELSA-Brasil
Authors: Cristina P Baena, Patricia Appelbaum, Paulo Andrade Lotufo, Itamar S Santos, Alessandra C Goulart, Isabela M Benseñor
Journal: Circulation (2019)

Introduction: Migraine with aura has been associated with cardiovascular events however the mechanisms are unclear. Arterial stiffness is a validated predictor of cardiovascular events and could play a role in that association. Hypothesis: We tested the hypothesis that migraine is associated with arterial stiffness in a well-defined middle-aged population. Methods: In a cross-sectional analysis of a well-defined population with complete and validated information about migraine and aura according to International Headache Society criteria, the arterial stiffness measured by carotid-to-femural pulse wave velocity was tested with multiple linear regression models comparing migraine without aura (MO) and migraine with aura (MA) to the reference group no migraine (NM) . Subsequent adjustments were made for age, sex, education, physical activity, alcohol use, diabetes, smoking, use of anti-hypertensive medication, waist circumference, LDL-cholesterol and triglycerides levels to test the independence of the association between migraine status and arterial stiffness. Results: We studied 4649 participants, 2521 women (25.7% MO and 15% MA)and 2128 men (11% MO and 4.3% MA). NM, MO and MA presented mean age 52.3 ±9.2 , 49.2 ± 7.7 and 47.9 ±7.1 years respectively (P&lt;0.001 for trend); mean systolic blood pressure 120.96 (±16.5), 117.35(±14.9) and 115 (±15.2) mmHg respectively (p&lt;0.001 for trend); mean fasting glucose 112.5 (± 29.37), 108.9(±30.7) and 103.12 (±24.6) mg/dl respectively (p&lt;0.001 for trend). Hypertension and diabetes were less prevalent in MA compared to NM (25,5% vs 33 % ) and (17.4% vs 21.3%) (p&lt;0.001 for both) and arterial stiffness was not significantly different across groups 9.22(±1.8), 9.28(±1.9) and 9.26(±2) m/s, respectively (p=0.746 for trend). Fully adjusted models yielded non-significant linear coefficients β (CI95%) 0.43 (-0.105;0.191)m/s when MA was compared with NM. Conclusion: In a large population of middle-aged with validated aura information, migraine status was not associated with arterial stiffness measured by carotid-to-femural pulse wave velocity.
Analysis of <i>FGFR</i> alterations from circulating tumor DNA (ctDNA) and Tissue in a phase II trial of erdafitinib in urothelial carcinoma (UC).
Authors: Ademi E. Santiago-Walker, Christopher Moy, Yauheniya Cherkas, Yohann Loriot, Arlene O. Siefker-Radtke, Clifford Motley, Anjali Narayan Avadhani, Anne OHagan, Peter De Porre, Matthew V. Lorenzi, Ian McCaffery
Journal: Journal of Clinical Oncology (2019)

420 Background: Plasma samples from a Phase 2 study of the pan-FGFR inhibitor erdafitinib in advanced UC patients (pts) with FGFR mutations (mut) or fusions, were tested using next generation sequencing (NGS) for circulating tumor DNA (ctDNA), and results compared to central FGFR status determination from tissue. Methods: FGFR alterations were measured in archival tissue using an RNA-based RT-PCR test and compared with FGFR alterations identified in pre-treatment plasma specimens using the Guardant360 ctDNA test. Sensitivity of the ctDNA test to detect the FGFR alterations identified by RT-PCR from tissue, the proportion of pts with a study-eligible FGFR alteration in ctDNA, and the ability to detect a tissue FGFR alteration in ctDNA in relation to clinical response were assessed. Results: Samples from 155 pts with detectable baseline ctDNA were included. Overall, concordance between ctDNA and tissue-based FGFR results was 56% (87/155): 63% (77/122) for tissue mut-positive pts vs 24% (7/29) in fusion-positive pts. 61% of pts (94/155) were positive for a study-eligible FGFR alteration from blood-based testing in the tissue-positive population. The response rate was 47% (36/77) for patients for which FGFR mutations could be detected in blood (ctDNA- FGFR-positive) compared with 32% (14/44) in patients for which mutations were not detected in blood (ctDNA- FGFR-negative), with an estimated odds ratio of 1.882 (95% CI: 0.866; 4.090) Conclusions: The 63% concordance rate for detecting FGFR mut in temporally unmatched blood and tissue supports potential for patient selection with blood-based testing, while ctDNA FGFR fusion detection may require further optimization. Although differences in clinical response rate were observed between ctDNA- FGFR-positive and negative patients, the results were not statistically significant. Importantly, a proportion of ctDNA-negative pts responded to erdafitinib, indicating that tissue-based testing may be warranted for pts negative for FGFR alterations via blood-based testing. (BLC2001, NCT02365597). Clinical trial information: NCT02365597.
Serum IgM/Fcmr Interactions Inhibit BCR Signaling and Influence the Cinical Course of CLL
Authors: Stefania Gobessi, Luca Laurenti, Fabiola Porro, Claudio Martines, Rosa Fazio, Elena Xerxa, Idanna Innocenti, Antonella Zucchetto, Shih-Shih Chen, Xiao-Jie Yan, Nicholas Chiorazzi, Valter Gattei, Dimitar G Efremov
Journal: Blood (2018)
RespondR: A genomic score to predict the responsiveness of triple-negative breast cancer patients to chemotherapy.
Authors: Steven Buechler, Yesim Gokmen-Polar, Sunil S. Badve
Journal: Journal of Clinical Oncology (2015)

1020 Background: A significant number of triple-negative breast cancer (TNBC) patients achieve pathological complete response (pCR) and improved relapse free survival from neoadjuvant taxane-anthracycline (AT) based chemotherapy. However, the 3-year distant relapse free survival (DRFS) probability for AT-treated TNBC patients is only about 0.50. A test is needed that identifies the AT-insensitive patients who are candidates for an alternative therapy. Methods: Gene expression measurements of 242 AT-treated TNBC patients were divided into training and validation sets balanced for clinical traits and pCR. An innovative multistate gene methodology was used to identify predictors of pCR in the training set and confirmed in validation set, along with higher DRFS in the predicted TF-sensitive group. Results: Analysis of the training set (n = 129; 38 pCR) identified 15 genes that were most predictive of pCR. RespondR Score was developed using these genes to continuously stratify patients by probability of pCR. In the validation set (n = 133; 60 pCR), RespondR stratifies patients into groups of low (RR-low, 55%), moderate (RR-moderate, 21%) and high (RR-high, 24%) sensitivity with rate of pCR 0.24 (RR-low), 0.29 (RR-moderate), 0.62 (RR-high) and 5-year DRFS probability 0.49 (RR-low), 0.61 (RR-moderate) and 0.80 (RR-high). In the RR-high group mitosis-related genes are up-regulated and genes involved in extracellular matrix organization and cell adhesion are down-regulated. Conclusions: The RespondR Score accurately predicts those TNBC patients likely to achieve pCR and improved survival using AT neoadjuvant chemotherapy. RespondR can provide critical information to patients and physicians deciding between AT and an alternative therapy.
Abstract 047: Sedentary Behavior Increases Risk for Cardiovascular Disease in Older Women: The Objective Physical Activity and Cardiovascular Health (OPACH) Study
Authors: John Bellettiere, Michael J LaMonte, Eileen Rillamas-Sun, Jacqueline Kerr, Kelly R Evenson, I-Min Lee, Chongzhi Di, David Buchner, Melbourne F Hovell, Andrea Z LaCroix
Journal: Circulation (2018)

Background: Evidence on sedentary behavior and cardiovascular disease (CVD) is largely based on self-reported sedentary time. Furthermore, how sedentary time is accumulated (in longer vs. shorter bouts) may be related to CVD risk but has not been tested. Methods: Women (n=5638, mean age=79±7) with no history of myocardial infarction or stroke wore accelerometers for 4-7 days and were followed for up to 4 years for incident CVD. Hazard ratios (HR) and 95% confidence intervals (CIs) for CVD and coronary heart disease (CHD) events were estimated across quartiles of sedentary time and mean sedentary bout duration using Cox proportional hazard models adjusting for covariates. Separate models evaluated associations after adding moderate-to-vigorous physical activity (MVPA) and possible mediators: body mass index, diabetes, hypertension, systolic blood pressure, fasting glucose, HDL-cholesterol, and triglycerides. We then tested whether mean bout duration was associated with increased risk for CVD and CHD among women with above median sedentary time (≥10hr/day). Results: Covariate-adjusted HRs for CVD and CHD increased across quartiles of both sedentary time and mean bout duration (Table). All CHD associations remained significant but attenuated after adjustment for possible mediators. After adjustment for MVPA, highest vs. lowest quartile HRs (CI) for CHD were 1.6 (0.7-3.4; p-trend = .08) for sedentary time and 1.8 (0.9-3.5; p-trend = .047) for mean bout duration. Among women with high sedentary time, the HRs (CI) comparing the 75 th vs. 25 th percentile of mean bout duration were 1.05 (0.95-1.15) for CVD and 1.16 (1.01-1.34) for CHD. Conclusions: Both sedentary time and mean bout duration showed independent, dose-response associations with increased risk of CVD and CHD events in older women. Among women with high sedentary time, longer mean bout duration was associated with higher CHD risk. Taken together, this provides evidence that both total sedentary time and the way it is accumulated are predictive of incident CHD.
Abstract MP55: Racial Differences in Metabolomic Profiles Between African Americans and Whites in the Women’s Health Initiative
Authors: Jie Hu, Raji Balasubramanian, Jun Li, Clary B Clish, Nina P Paynter, Christine M Albert, Simin Liu, Milagros C Rosal, Rami Nassir, Kathryn M Rexrode
Journal: Circulation (2019)

Introduction: In the US, African Americans (AA) have higher cardiovascular disease (CVD) morbidity and mortality than whites. Recent evidence suggests that the CVD development may be related to circulating metabolite alterations, which might contribute to racial disparities in CVD risk. Hypothesis: We tested the hypothesis that metabolomic profile of AAs differ from that of whites. Methods: Metabolomic profiling in plasma samples of 2,128 women from the Women’s Health Initiative (WHI) was performed using liquid chromatography-tandem mass spectrometry, and 422 known metabolites were measured. The discovery set included 834 women (138 AAs) from the WHI Observational Study. The replication set included 1,294 women (156 AAs) from the WHI Hormone Therapy Trials. Linear regression models were applied to individually estimate the association of race (AA vs. white) with each metabolite, adjusting for age, body mass index, education, income, healthy eating index-2005, physical activity, smoking, alcohol intake, hypertension, diabetes, depression, and medications. Metabolites with a false discovery rate-adjusted P &lt;0.05 in the discovery set were then replicated in the replication set with a Bonferroni corrected P &lt;0.05 indicating statistical significance. Results: We identified 178 metabolites that significantly differed between AAs and whites in both discovery and replication sets, the majority of which were lipids, followed by amino acids and their derivatives (Panel A). For the 178 metabolites, the mean levels of 126 metabolites differed between AAs and Whites by at least 0.5 standard deviation units; 9 of these metabolites (1 triacylglycerol, 3 phosphatidylcholines, 2 phosphatidylethanolamine plasmalogens, and 3 cholesteryl esters) had mean differences exceeding 1-standard deviation unit (Panel B). Conclusions: Metabolomic profiles significantly differed between AAs and whites, especially lipid metabolites, and these race-associated alterations may contribute to racial disparities in cardiovascular risk.
Amikacin Liposome Inhalation Suspension: A Review in Mycobacterium avium Complex Lung Disease
Authors: Matt Shirley
Journal: Drugs (2019)

Amikacin liposome inhalation suspension (ALIS; Arikayce®) [formerly known as liposomal amikacin for inhalation, or LAI] is a liposomal formulation of the aminoglycoside antibacterial drug amikacin. The ALIS formulation, administered via inhalation following nebulization, is designed to facilitate targeted and localized drug delivery to the lungs while minimizing systemic exposure. Based on the prespecified primary endpoint analysis of the ongoing phase III CONVERT trial, ALIS has been approved in the USA for use as part of a combination antibacterial drug regimen against Mycobacterium avium complex (MAC) lung disease that is treatment refractory (i.e. an active infection present despite ≥ 6 consecutive months of a multidrug regimen) in adult patients who have limited or no alternative treatment options. In the CONVERT trial, once-daily ALIS as an add-on to guidelines-based therapy (GBT) significantly increased the odds of achieving sputum culture conversion by month 6 compared with GBT alone in patients with treatment-refractory MAC lung disease. The addition of ALIS to GBT was associated with an increased risk of respiratory adverse events compared with GBT alone; however, serious adverse events were experienced by a similar proportion of patients in the two treatment groups. In conclusion, although current evidence for efficacy is limited to microbiological outcomes (with clinical benefit yet to be established), available data suggest that ALIS is a useful option for the treatment of patients with MAC lung disease who have not responded to conventional therapy and for whom there are limited or no alternative treatment options available.
Role of magnetic resonance imaging-transrectal ultrasound fusion targeted biopsy in the detection of prostate cancer in biopsy-naïve men: A literature based meta-analysis of randomized trials.
Authors: Xiang Tu, Zhenhua Liu, Shi Qiu, He Xu, Jiakun Li, Xinyang Liao, Kun Jin, Yige Bao, Lu Yang, Qiang Wei
Journal: Journal of Clinical Oncology (2019)

70 Background: Magnetic Resonance Imaging-Transrectal Ultrasound (MRI/TRUS) fusion targeted biopsy (TB) has been demonstrated to increase detection rates (DRs) of prostate cancer (PCa) in repeat-biopsy setting. However, its role in biopsy-naïve men remains controversial. We performed a meta-analysis based on well-designed randomized controlled trials (RCTs) to compare the diagnostic accuracy of MRI/TRUS fusion TB and systematic biopsy (SB) in the detection of PCa in biopsy-naïve men. Methods: A systematic review of PubMed (Medline), Embase, Ovid and the Cochrane Library up to 1 st October, 2018 was conducted. The statistical analyses were performed with Revman 5.3. We compared the diagnostic accuracy between the intervention group (assisted with fusion TB) and the control group (SB only) by calculating the risk ratio (RR) with 95% confidence intervals (CIs) of overall PCa and clinically significant PCa (csPCa) DRs. Subgroup analysis was performed to highlight the independent role of MRI/TRUS fusion TB alone or combining fusion TB and SB together in the detection of PCa. Results: Six RCTs with 2187 participants were evaluated for the DRs of overall PCa. Pooled analysis revealed slight higher DRs of 62.7% (687/1095) in the intervention group compared with that of 41.3% (451/1092) in the control group (RR 1.40, 95% CI: 1.00-1.95). Four studies with 962 participants were evaluated for the DRs of csPCa. There is a trend favoring the intervention group which detected more csPCa (42.8%, 206/481) compared with SB in the control group (31.6%, 152/481) but with no significant difference (RR 1.36, 95% CI: 0.95-1.95). Subgroup analysis revealed fusion TB alone with less biopsy cores may equal the DRs of csPCa compared with SB alone (RR 1.24, 95% CI: 0.79-1.93). However, the DRs of overall PCa when combining MRI/TRUS fusion TB and SB was comparable to that applying SB alone (RR 1.48, 95% CI: 0.99-2.22). Conclusions: MRI/TRUS fusion TB may obtain similar csPCa DRs with less biopsy cores. But currently there was no enough evidence showing fusion TB can help significantly improve overall PCa or csPCa DRs compared with SB alone in biopsy-naïve men.