tbuckley/cabot-search huggingface dataset:
Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer
Authors: Tanya E. Keenan, Tianyu Li, Tuulia Vallius, Jennifer L. Guerriero, Nabihah Tayob, Bose Kochupurakkal, Janae Davis, Ricardo Pastorello, Rie K. Tahara, Leilani Anderson, Jake Conway, Meng X. He, Erin Shannon, Robert E. Godin, Peter K. Sorger, Alan D'Andrea, Beth Overmoyer, Eric P. Winer, Elizabeth A. Mittendorf, Eliezer M. Van Allen, Geoffrey I. Shapiro, Sara M. Tolaney
Journal: Clinical Cancer Research (2020)

We report results from a phase II study assessing the efficacy of the WEE1 inhibitor adavosertib with cisplatin in metastatic triple-negative breast cancer (mTNBC).Patients with mTNBC treated with 0-1 prior lines of chemotherapy received cisplatin 75 mg/m2 i.v. followed 21 days later by cisplatin plus adavosertib 200 mg oral twice daily for five doses every 21 days. The study had 90% power to detect the difference between null (20%) and alternative (40%) objective response rates (ORR) with a one-sided type I error of 0.1: an ORR >30% was predefined as making the regimen worthy of further study. RNA sequencing and multiplex cyclic immunofluorescence on pre- and post-adavosertib tumor biopsies, as well as targeted next-generation sequencing on archival tissue, were correlated with clinical benefit, defined as stable disease ≥6 months or complete or partial response.A total of 34 patients initiated protocol therapy; median age was 56 years, 2 patients (6%) had BRCA2 mutations, and 14 (41%) had one prior chemotherapy. ORR was 26% [95% confidence interval (CI), 13-44], and median progression-free survival was 4.9 months (95% CI, 2.3-5.7). Treatment-related grade 3-5 adverse events occurred in 53% of patients, most commonly diarrhea in 21%. One death occurred because of sepsis, possibly related to study therapy. Tumors from patients with clinical benefit demonstrated enriched immune gene expression and T-cell infiltration.Among patients with mTNBC treated with 0-1 prior lines, adavosertib combined with cisplatin missed the prespecified ORR cutoff of >30%. The finding of immune-infiltrated tumors in patients with clinical benefit warrants validation.
Neurological telemedicine in the COVID-19 era
Authors: Victor Patterson
Journal: Nature Reviews Neurology (2020)

Many neurologists have used telemedicine during the COVID-19 pandemic. Studies have shown that videolinks in acute care can save personal protective equipment and protect staff. Furthermore, the telephone can provide supra-hospital care in Parkinson disease and manage patients with amyotrophic lateral sclerosis well. The primacy of face-to face care has been dented.
The COVID-19 pandemic: consequences for nephrology
Authors: Annette Bruchfeld
Journal: Nature Reviews Nephrology (2020)

The consequences of the COVID-19 pandemic have been devastating; however, evidence suggests that patients with, or at risk of, kidney disease are disproportionally affected. Patients on dialysis and kidney transplant recipients are at higher risk of adverse outcomes from COVID-19, whereas, conversely, patients with severe COVID-19 are at increased risk of acute kidney injury, with short-term and possibly long-term consequences for nephrological care.
Long-term efficacy and safety of ixekizumab: A 5-year analysis of the UNCOVER-3 randomized controlled trial
Authors: Andrew Blauvelt, Mark G. Lebwohl, Tomotaka Mabuchi, Ann Leung, Alyssa Garrelts, Heidi Crane, Hany ElMaraghy, Himanshu Patel, Terri Ridenour, Kyoungah See, Gaia Gallo, Carle Paul
Journal: Journal of the American Academy of Dermatology (2020)

ObjectiveTo report the efficacy and safety of the approved ixekizumab (IXE) dose over 5 years from UNCOVER-3 (NCT01646177).MethodsPatients (N = 1346) were randomized 1:2:2:2 to receive subcutaneous injections of placebo, etanercept 50 mg twice weekly, or IXE 80 mg every 2 weeks or every 4 weeks after an initial dose of IXE 160 mg, respectively. At week 12, patients entered the long-term extension period with dosing of IXE every 4 weeks and could escalate to every 2 weeks after week 60. Efficacy was reported for the IXE every 2 weeks/every 4 weeks group of the intent-to-treat population. Safety was reported for patients who received at least 1 dose of IXE every 2 or every 4 weeks.ResultsUsing modified nonresponder imputation, 78.8%/67.1%/46.2% of patients receiving the approved dose of IXE every 2 weeks/every 4 weeks (n = 385) achieved ≥75%, ≥90%, or 100% improvement from baseline in the Psoriasis Area and Severity Index, respectively, at week 264; static Physician's Global Assessment score of 0/1 and 0 responses were 69.2% and 45.3%, respectively. Infections were the most observed treatment-emergent adverse event (72.7% of patients).LimitationsLack of comparison treatment group after week 12.ConclusionIXE demonstrates sustained efficacy and consistent safety through 264 weeks in patients using the approved dose. To report the efficacy and safety of the approved ixekizumab (IXE) dose over 5 years from UNCOVER-3 (NCT01646177). Patients (N = 1346) were randomized 1:2:2:2 to receive subcutaneous injections of placebo, etanercept 50 mg twice weekly, or IXE 80 mg every 2 weeks or every 4 weeks after an initial dose of IXE 160 mg, respectively. At week 12, patients entered the long-term extension period with dosing of IXE every 4 weeks and could escalate to every 2 weeks after week 60. Efficacy was reported for the IXE every 2 weeks/every 4 weeks group of the intent-to-treat population. Safety was reported for patients who received at least 1 dose of IXE every 2 or every 4 weeks. Using modified nonresponder imputation, 78.8%/67.1%/46.2% of patients receiving the approved dose of IXE every 2 weeks/every 4 weeks (n = 385) achieved ≥75%, ≥90%, or 100% improvement from baseline in the Psoriasis Area and Severity Index, respectively, at week 264; static Physician's Global Assessment score of 0/1 and 0 responses were 69.2% and 45.3%, respectively. Infections were the most observed treatment-emergent adverse event (72.7% of patients). Lack of comparison treatment group after week 12. IXE demonstrates sustained efficacy and consistent safety through 264 weeks in patients using the approved dose.
Trends in Hospitalizations for Heart Failure and Ischemic Heart Disease Among US Adults With Diabetes
Authors: Michael C. Honigberg, Ravi B. Patel, Ambarish Pandey, Gregg C. Fonarow, Javed Butler, Darren K. McGuire, Muthiah Vaduganathan
Journal: JAMA Cardiology (2020)

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Cardiovascular risk factors in China: a nationwide population-based cohort study
Authors: Xi Li, Chaoqun Wu, Jiapeng Lu, Bowang Chen, Yichong Li, Yang Yang, Shengshou Hu, Jing Li
Journal: The Lancet Public Health (2020)

It is estimated that 4 million deaths are due to cardiovascular diseases each year in China. Comprehensive understanding about modifiable risk factors and how the risk differs across regions is needed to inform public health policies. We aimed to examine the geographical profile of cardiovascular disease risk across China.In this study, we analysed data from a nationwide, population-based screening project, which covered 152 rural counties and 100 urban districts from 31 provinces in China. Between Sept 1, 2015, and Nov 30, 2019, standardised measurements were taken from participants aged 35-75 years who had lived in the region for at least 6 of the preceding 12 months to collect information on blood pressure, blood lipids, blood glucose, physical activity, tobacco smoking, alcohol use, overweight or obesity, and intake frequencies of fruits, vegetables, whole grains, legumes, and red meat. Individuals with a high risk of cardiovascular disease were identified according to medical history and WHO risk prediction charts.983 476 individuals were included in this study. Among the participants included, 10·3% (95% CI 10·2-10·3) had a high cardiovascular disease risk after standardising age and sex, with a range of 3·1-24·9% across counties or districts. Among the seven regions in mainland China, the prevalence of high risk of cardiovascular disease was relatively high in northeast China (12·6% [12·4-12·8]) and north China (11·4% [11·3-11·6]), whereas it was low in south China (8·0% [7·8-8·2]). The geographical profiles of the 12 major cardiovascular disease risk factors were different. We found that the regions with high cardiovascular disease risk were facing challenges such as obesity and high blood pressure (north China) and consumption of unhealthy non-staple food (low intake of fruits and vegetables or high intake of red meat; northeast China). By contrast, south China-the region with the lowest cardiovascular disease risk-had the highest prevalence of unhealthy staple food (low intake of whole grains and beans), abnormal metabolism (glucose and lipid), and low physical activity in the country.Risk for cardiovascular diseases varies geographically, and the major contributing risk factors are different across regions in China. Hence, geographically targeted interventions are needed to mitigate the risk and reduce the burden in such a vast country.Ministry of Science and Technology, Ministry of Finance, and National Health Commission of China.
New rule allows US government to execute prisoners by means other than lethal injection
Authors: Owen Dyer
Journal: BMJ (2020)

A new rule created by the Trump administration will allow the US federal government to execute its death row prisoners by any method approved in states that have the death penalty. The change could potentially allow the US government to execute people by electric chair, firing squad, or the method increasingly embraced by death penalty advocates, nitrogen asphyxiation.

The rule, to be published in the federal register on 27 November after a compressed public comment period,1 alters regulations set out in 1993, when lethal injection was widespread and easily carried out.

Those rules stipulated that federal prisoners facing the death penalty would be executed according to the existing protocol of the state …
Transesophageal Echocardiography Before Atrial Fibrillation Ablation: Looking Before Cooking⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Bradley P. Knight
Journal: Journal of the American College of Cardiology (2009)
Abstract 15952: Gut Microbiota and Insulin Resistance in Heart Failure
Authors: Petra Mamic, Samuel Lancaster, Michael Snyder
Journal: Circulation (2020)

Introduction/Hypothesis: Insulin resistance (IR) and heart failure (HF) are closely interconnected - IR is a risk factor for HF and can develop as a consequence of chronic HF. Dysregulation of the gut microbiota (GMB) has been independently associated with both HF and IR, with many overlapping GMB features. We hypothesized that the HF-associated GMB changes may be confounded by concomitant IR. Methods: Our study recruited 60 non-diabetic adults with non-ischemic cardiomyopathy and HF. As controls we included 49 non-diabetic adults. We profiled GMB using whole genome sequencing. Degree of IR was assessed by fasting Homeostatic Model Assessment of IR (HOMA-IR). Results: Study participants were largely middle aged (median age 53.6 years), white (65%), and overweight (median body mass index (BMI) 28.5 kg/m2). Men were over-represented in the HF group, compared to controls (78% vs 48%). Mean left ventricular ejection fraction was 30.5% in the HF group, and most HF patients had mild symptoms. Both groups had elevated HOMA-IR (median 2.5). According to beta-diversity analysis based on Bray-Curtis distances, both taxonomic and functional GMB structure were significantly different in HF, compared to controls (ANOSIM p&lt;0.001) (Figure 1). Similar analysis of IR-associated GMB structure did not show significant separation (Figure 2). Taxa and metabolic pathways contributing to HF-associated GMB differences (Table 2) remained significant after controlling for HOMA-IR, age, sex, race, and BMI. Conclusions: We confirmed independent association between HF and taxonomic and functional GMB community shifts, but did not demonstrate a direct relationship between comorbid IR (as measured by HOMA-IR) and the GMB changes in HF. More precise and accurate measurement of IR than HOMA-IR may be needed to allow better characterization of the GMB-IR relationship in HF, and hopefully enable identification of novel preventative, diagnostic, and therapeutic targets in this disease.
Plasmapheresis reduces cytokine and immune cell levels in COVID-19 patients with acute respiratory distress syndrome (ARDS)
Authors: Seyed MohammadReza Hashemian, Navid Shafigh, Golnaz Afzal, Hamidreza Jamaati, Payam Tabarsi, Majid Marjani, Majid Malekmohammad, Seyed Mehdi Mortazavi, Batoul Khoundabi, Davood Mansouri, Afshin Moniri, Abbas Hajifathali, Elham Roshandel, Esmaeil Mortaz, Ian M Adcock
Journal: Pulmonology (2020)

In December 2019, pneumonia associated with a novel coronavirus (COVID-19) was reported in Wuhan, China. Acute respiratory distress syndrome (ARDS) is the most frequently observed complication in COVID-19 patients with high mortality rates. To observe the clinical effect of plasmapheresis on excessive inflammatory reaction and immune features in patients with severe COVID-19 at risk of ARDS. In this single-center study, we included 15 confirmed cases of COVID-19 at Masih Daneshvari Hospital, in March 2020 in Tehran, Iran. COVID-19 cases were confirmed by RT-PCR and CT imaging according to WHO guidelines. Plasmapheresis was performed to alleviate cytokine-induced ARDS. The improvement in oxygen delivery (PaO2/FiO2), total number of T cells, liver enzymes, acute reaction proteins, TNF-α and IL-6 levels were evaluated. Inflammatory cytokine levels (TNF-α, IL-6), and acute phase reaction proteins including ferritin and CRP were high before plasmapheresis. After plasmapheresis, the levels of PaO2/FiO2, acute phase reactants, inflammatory mediators, liver enzymes and bilirubin were significantly reduced within a week (p < 0.05). In contrast, although the number of T helper cells decreased immediately after plasmapheresis, they rose to above baseline levels after 1 week. Nine out of fifteen patients on non-invasive positive-pressure ventilation (NIPPV) survived whilst the six patients undergoing invasive mechanical ventilation (IMV) died. Our data suggests that plasmapheresis improves systemic cytokine and immune responses in patients with severe COVID-19 who do not undergo IMV. Further controlled studies are required to explore the efficacy of plasmapheresis treatment in patients with COVID-19.
OP0077 Ultrasound in the diagnosis of discus herniation
Authors: TH Hansen, S Torp-Pedersen, E Quistgaard, J Boesen, H Bliddal, B Danneskiold-Samsoe
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> One major advantage of ultrasound (US) is that it can be performed bedside by the clinician. In an attempt to implement US in the diagnosis of disc herniation some authors have previously described sensitivities and specificities approximating those of the conventional methods. Within the last decade, however, there have only been sparse reports on this subject. So far, the role of US in this area is unclear. <h3>Objectives</h3> To evaluate in a blinded fashion US in the diagnosis of disc herniations at the three lower lumbar levels performed by an experienced specialist. <h3>Methods</h3> 18 males and 19 females with a mean age of 39.7 years (SD 10.5 years) and no previous back surgery were included due to suspected disc herniation. The US was performed transabdominally with the patient in the supine position. An Acuson Sequoia with a 4 MHz vector transducer was used. MRI or CT was obtained at the three lower lumbar levels. The two modalities (US vs. CT/MRI) were performed and evaluated blinded to each other. The endpoints were existence of herniation or protrusion in contrast to normal findings and the corresponding level of the abnormal finding. <h3>Results</h3> A total of 97 disc levels were visualised by US. Fourteen levels were not visualised. There were 45 disc abnormalities (herniations or protrusions) found by CT/MRI, and of those 12 (26.7%) were also found by US. Fifty two discs were found to be normal by CT or MRI, but of those 11 (21.2%) were suspected to be abnormal by US. A total agreement between US and CT/MRI was found in 53/97 (54.6%) of the cases. The sensitivity of US was 12/45 (26.7%) and the specificity 12/23 (52.2%). The false positive rate was 47.8% and the false negative rate 44.6%. The over all kappa value was 0.18. The findings stratified at levels are shown in the Table 1. The kappa value for level L5/S1 was -0.18 and the kappa value for the levels L3/4 and L4/5 were 0.13 and 0.25 respectively. At levels L3/4 and L4/5 a total agreement of 40/63 was found. <h3>Conclusion</h3> At level L5/S1 US does not seem to be of any diagnostic value. At the levels L3/4 and L4/5 US was in agreement with CT/MRI in about 2/3 of the patients and could be of potential use at these levels. Further investigations are needed to establish the role of US. <h3>References</h3> Hagen A, Tertsch D, Schön R, Richwien R. Die spinale ultraschalltomographie in der diagnostik des lumbalen bandscheibenvorfalls. Zbl Neurochir 1987;48:280–4 Tervonen O, Lähde S, Vanharanta H. Ultrasound diagnosis of lumbar disc degeneration. Comparison with computed tomography/discography. Spine 1990;16(8):951–8
Incidental Findings of a Vestibular Schwannoma on 18F-Choline PET/CT
Authors: Karim Amrane, Romain Le Pennec, Valentin Tissot, Ulrike Schick, Ronan Abgral
Journal: Clinical Nuclear Medicine (2020)

We report an increased uptake of 18F-choline in the right cerebellopontine angle area in a 73-year-old man with biochemical failure prostate cancer after radical prostatectomy, potentially suggestive of bone metastasis in the base of the skull. A brain MRI was also performed showing an intense gadolinium enhancement focus in the same area, concordant with a right vestibular schwannoma, subsequently histologically proven. This case underlines that schwannoma is a diagnostic pitfall in 18F-choline PET/CT, suggesting this radiolabeled tracer as a promising tool for brain tumors characterization due to its higher signal-to-background ratio than 18F-FDG.
15262 Cardio-metabolic effects of long-term treatment with secukinumab in psoriatic arthritis and ankylosing spondylitis patients: Pooled 3 year analysis
Authors: Iain B. McInnes, Dafna D. Gladman, Atul A. Deodhar, Corinne Miceli-Richard, Peter Nash, Naveed Sattar, Nehal N. Mehta, Jianyuan Wang, Luminita Pricop, Gabriele di Comite
Journal: Journal of the American Academy of Dermatology (2020)
Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials
Authors: Thierry André, Jeffrey Meyerhardt, Timothy Iveson, Alberto Sobrero, Takayuki Yoshino, Ioannis Souglakos, Axel Grothey, Donna Niedzwiecki, Mark Saunders, Roberto Labianca, Takeharu Yamanaka, Ioannis Boukovinas, Dewi Vernerey, Jeffrey Meyers, Andrea Harkin, Valter Torri, Eiji Oki, Vassilis Georgoulias, Julien Taieb, Anthony Shields, Qian Shi
Journal: The Lancet Oncology (2020)
An independent external validation of melanoma risk prediction models using the Australian Melanoma Family Study
Authors: K. Vuong, B.K. Armstrong, D. Espinoza, J.L. Hopper, J.F. Aitken, G.G. Giles, H. Schmid, G.J. Mann, A.E. Cust, K. McGeechan
Journal: British Journal of Dermatology (2020)

Risk prediction models, which include a combination of risk factors, have been developed as a more accurate way of estimating risk and personalising preventive interventions. Many melanoma risk prediction models have been published but few have been independently validated.1 We aimed to externally validate 12 melanoma risk prediction models using the Australian Melanoma Family Study (AMFS), a population-based, case-control-family study comprising 629 incident first-primary melanoma cases, 240 population-based controls ascertained using the electoral roll (voting is compulsory) and 295 spouse or friend controls.2 Recruitment took place from 2001 to 2005 in the states of New South Wales, Queensland and Victoria.
Isolated periocular oedema
Authors: Hugo Toth, Sébastien Abad
Journal: BMJ (2020)

This man in his 50s has anti-melanoma differentiation associated protein 5 (anti-MDA5) dermatomyositis.

Over three months the patient had experienced gradually worsening, painful, bilateral, periocular oedema. On examination, almost full palpebral obstruction was …
Histone H3 G34 Tail Mutations in Cancer: Actions in <i>Cis</i> and <i>Trans</i> to Alter Chromatin and Gene Expression
Authors: Jonathan D. Licht
Journal: Cancer Discovery (2020)

Abstract Summary: Sequencing of cancer genomes has demonstrated that driver mutations occur in every component of the transcriptional machinery including histones that comprise the nucleosome. Histone mutations may affect the “tail” residues subject to post-translational modification and can compromise the structural integrity of the histone octamer. See related article by Khazaei et al., p. 1968.
Cardiac Structure and Function in Elite Female and Male Soccer Players
Authors: Timothy W. Churchill, Bradley J. Petek, Meagan M. Wasfy, James S. Guseh, Rory B. Weiner, Tamanna K. Singh, Christian Schmied, Hughie O’Malley, George Chiampas, Aaron L. Baggish
Journal: JAMA Cardiology (2020)

Population-specific normative data are essential for the evaluation of competitive athletes. At present, there are limited data defining normal electrocardiographic (ECG) and echocardiographic values among elite US soccer players.To describe ECG and echocardiographic findings in healthy elite US soccer players.This cross-sectional study analyzed Fédération Internationale de Football Association-mandated screening sessions performed at US Soccer National Team training locations from January 2015 to December 2019. US women's and men's national team soccer players undergoing mandated cardiovascular screening were included.Normal training-related and abnormal ECG findings were reported using the International Recommendations for Electrocardiographic Interpretation in Athletes. Echocardiographic measurements of structural and functional parameters relevant to cardiovascular remodeling were assessed relative to American Society of Echocardiography guideline-defined normal ranges.A total of 238 athletes (122 [51%] female; mean [SD] age, 20 [4] years; age range, 15-40 years) were included. Male athletes demonstrated a higher prevalence of normal training-related ECG findings, while female athletes were more likely to have abnormal ECG patterns (14 [11%] vs 0 in male cohort), largely accounted for by abnormal T-wave inversions. Echocardiography revealed no pathologic findings meeting criteria for sport restriction, but athletes frequently exceeded normal ranges for structural cardiac parameters responsive to exercise-induced remodeling including body surface area-indexed left ventricular (LV) mass (58 of 113 female athletes [51%] and 67 of 114 male athletes [59%]), indexed LV volume (89 of 115 female athletes [77%] and 76 of 111 male athletes [68%]), and LV wall thickness (37 of 122 female athletes [30%] and 47 of 116 male athletes [41%]). Age-stratified analysis revealed age-dependent increases in LV wall thickness, mass, and volumes among female athletes and LV wall thickness and mass among male athletes.These data represent the first set of comprehensive normative values for elite US soccer players and one of the largest sport-specific echocardiographic remodeling studies in female athletes. Abnormal ECG findings were more common in female athletes, while both female and male athletes frequently exceeded clinical normality cut points for remodeling-associated echocardiographic parameters.