tbuckley/cabot-search huggingface dataset:
Transcriptomic changes during stage progression of mycosis fungoides
Authors: M.Z.X. Xiao, D. Hennessey, A. Iyer, S. O’Keefe, F. Zhang, A. Sivanand, R. Gniadecki
Journal: British Journal of Dermatology (2021)

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, which in the early patch/plaque stages runs an indolent course. However, ~25% of patients with MF develop skin tumours, a hallmark of progression to the advanced stage, which is associated with high mortality. The mechanisms involved in stage progression are poorly elucidated.We sought to address the hypothesis of MF cell trafficking between skin lesions by comparing transcriptomic profiles of skin samples in different clinical stages of MF.We performed whole-transcriptome and whole-exome sequencing of malignant MF cells from skin biopsies obtained by laser-capture microdissection. We compared three types of MF lesions: early-stage plaques (ESP, n = 12) as well as plaques and tumours from patients in late-stage disease [late-stage plaques (LSP, n = 10) and tumours (TMR, n = 15)]. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to determine pathway changes specific for different lesions which were linked to the recurrent somatic mutations overrepresented in MF tumours.The key upregulated pathways during stage progression were those related to cell proliferation and survival (MEK/ERK, Akt-mTOR), T helper cell (Th)2/Th9 signalling [interleukin (IL)4, STAT3, STAT5, STAT6], meiomitosis (CT45A1, CT45A3, STAG3, GTSF1, REC8) and DNA repair (PARP1, MYCN, OGG1). Principal coordinate clustering of the transcriptome revealed extensive gene expression differences between early (ESP) and advanced-stage lesions (LSP and TMR). LSP and TMR showed remarkable similarities at the level of the transcriptome, which we interpreted as evidence of cell percolation between lesions via haematogenous self-seeding.Stage progression in MF is associated with Th2/Th9 polarization of malignant cells, activation of proliferation, survival, as well as increased genomic instability. Global transcriptomic changes in multiple lesions may be caused by haematogenous cell percolation between discrete skin lesions.
Heterogeneity in Neurodevelopmental Outcomes Associated With Isolated Sagittal Craniosynostosis
Authors: Brent R. Collett
Journal: JAMA Network Open (2021)

Amanda J. Osborn, PhD; Rachel M. Roberts, PhD; Diana S. Dorstyn, PhD; Ben G. Grave, MBBS, MASurg(Craniofacial); David J. David, MD, MBBS
Associations of inflammatory, oxidative stress, and cardiac damage biomarkers and radiation-induced fatigue in breast cancer survivors.
Authors: Alexi Vasbinder, Hilaire Thompson, Oleg Zaslavsky, Susan R. Heckbert, Rowan T. Chlebowski, Aladdin H. Shadyab, Nazmus Saquib, Lisa Warsinger Martin, Electra D. Paskett, Kerryn Reding
Journal: Journal of Clinical Oncology (2021)

191 Background: Radiation-induced fatigue (RIF) is common in breast cancer (BC) survivors and can last years after treatment. Despite the known physiological consequences of radiation, information on biomarkers of RIF is limited. Therefore, we examined the longitudinal association between serum biomarkers and post-BC fatigue in BC survivors treated with radiation: [oxidative stress] 8-hydroxyguanosine (8-OH-dG), myeloperoxidase (MPO); [inflammation] interleukin-6 (IL-6), C-reactive protein (CRP), growth differentiation factor-15 (GDF-15), placental growth factor (PGF), transforming growth factor-beta (TGF-B); [cardiac damage] cystatin-C, troponin-I (TnI). Methods: In an ancillary study in the Women’s Health Initiative (WHI), participants with incident BC (stages I-III) treated with radiation were followed for the development of fatigue post-BC. Women were eligible if they 1) had no prior cardiovascular disease and 2) had pre-and post-BC serum samples drawn approximately three years apart with fatigue measured using the Short-Form 36 (SF-36) vitality subscale at the same times. Biomarkers were analyzed using enzyme-linked immunosorbent assays. Higher SF-36 vitality scores correspond to lesser fatigue. Weighted linear regression adjusted for relevant demographic, lifestyle, and psychosocial factors, as well as pre-cancer fatigue. Each biomarker was modeled as the post-BC to pre-BC ratio and log transformed to base 2, thus, the effect estimates correspond to a doubling in value compared to pre-BC. Results: A total of 180 women with a mean (SD) age of 67.0 (5.5) were included. The mean (SD) vitality score was 66.2 (17.2) and 59.7 (19.7) pre- and post-BC, respectively. The median (IQR) time between pre-BC serum collection to BC was 1.9 (0.8, 2.6) years and 1.4 (0.7, 2.3) years between BC and the post-BC serum collection. After adjustment, a higher biomarker ratio of cystatin-C, IL-6, and GDF-15 were all associated with a lower SF-36 vitality score (i.e., higher fatigue) (Table). As an example, for a 2-fold difference in the cystatin-C biomarker ratio, the SF-36 vitality score was lower by 7.31 points (95% CI: -14.2, -0.45). Conclusions: Inflammatory and cardiac damage biomarkers are associated with RIF in BC survivors. Biomarkers could be measured in clinical practice or be included in risk prediction models to help identify patients at high risk for RIF. [Table: see text]
A phase I/<scp>II</scp> study of ixazomib, pomalidomide, and dexamethasone for lenalidomide and proteasome inhibitor refractory multiple myeloma (Alliance <scp>A061202</scp>)
Authors: Peter M. Voorhees, Vera J. Suman, Sascha A. Tuchman, Jacob P. Laubach, Hani Hassoun, Yvonne A. Efebera, Flora Mulkey, Misty Bova‐Solem, Katelyn Santo, Destin Carlisle, Philip L. McCarthy, Paul G. Richardson
Journal: American Journal of Hematology (2021)

Preclinical studies have demonstrated activity of the oral proteasome inhibitor (PI) ixazomib (IXA) in bortezomib-resistant multiple myeloma (MM) and synergy with immunomodulatory drugs. We therefore conducted a phase I/II study to establish the safety and preliminary efficacy of IXA with pomalidomide (POM) and dexamethasone (DEX) in lenalidomide (LEN)/PI-refractory MM. Dose escalation established a 4 mg dose of POM and IXA and 20/40 mg dose of DEX as the maximum tolerated dose. The phase II portion of the trial was redesigned and started anew after six patients had been randomized to IXA-POM-DEX due to a rapidly changing treatment landscape. Among the 29 evaluable LEN/PI-refractory patients treated with IXA-POM-DEX in phase I/II, the overall response rate (partial response or better) was 51.7% with a median duration of response of 16.8 months (range 56 days to 4.1 years), median progression-free survival of 4.4 months (95% confidence interval [CI]: 3.0-18.4), and median overall survival of 34.3 months (95% CI: 19.2 to not reached). Hematologic, gastrointestinal, and constitutional adverse events were common and consistent with the side-effect profiles of the individual agents. Our results support further evaluation of this all-oral regimen in relapsed/refractory MM.
Neoadjuvant hormonal therapy before radical prostatectomy in high-risk prostate cancer
Authors: Gaëtan Devos, Wout Devlies, Gert De Meerleer, Marcella Baldewijns, Thomas Gevaert, Lisa Moris, Daimantas Milonas, Hendrik Van Poppel, Charlien Berghen, Wouter Everaerts, Frank Claessens, Steven Joniau
Journal: Nature Reviews Urology (2021)
Lingering Effects of Hyperglycemia in Recently Diagnosed Diabetes During Long-term Follow-up of the DCCT/EDIC and UKPDS Cohorts: More Evidence That Early Control Matters
Authors: Matthew C. Riddle, Hertzel C. Gerstein, Philip D. Home
Journal: Diabetes Care (2021)

The Diabetes Control and Complications Trial (DCCT) and the UK Prospective Diabetes Study (UKPDS) have given us fundamental insights into the natural history and management of diabetes (1,2). These include strong evidence that 1 ) enhanced glycemic management can limit some of the complications of diabetes, 2 ) there is a dose-response relationship between HbA1c levels and the risk of complications, and 3 ) a treatment target of <7.0% (<53 mmol/mol) HbA1c is realistic and appropriate. Continued observation of the randomized cohorts after the planned end of study has further shown that cardiovascular events and mortality, which could not be shown to be improved during the randomized treatment phases, were significantly reduced long after glucose control equalized in the two arms (3–5). In both studies glycemic control as assessed by HbA1c accounted statistically for most of the difference in outcomes.

In three articles in this issue of Diabetes Care the DCCT and UKPDS investigators provide more information on the long-term effects of enhanced glycemic control early in the natural history of diabetes (6–8). In the first of two articles based on more than 20 years of additional observation of the DCCT cohorts in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, Lachin and Nathan (6) report new analyses of data on microvascular complications. These add to previously reported evidence for persistence of lower rates of progression of microvascular disease in the originally intensively managed cohort, despite convergence of HbA1c values in the two groups soon after cessation of the randomized comparison of treatments. The investigators have previously termed this phenomenon “metabolic memory.” Here they further report a gradual waning of outcome differences after ∼10 years. They emphasize a distinction between the incremental effect on microvascular complications, which slowly declines, and the cumulative …
Parent Preferences for Transparency of Their Child’s Hospitalization Costs
Authors: Hannah K. Bassett, Jimmy Beck, Ryan J. Coller, Brian Flaherty, Kristin A. Tiedt, Kevin Hummel, Michael J. Tchou, Kristopher Kapphahn, Lauren Walker, Alan R. Schroeder
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Health care in the US is often expensive for families; however, there is little transparency in the cost of medical services. The extent to which parents want cost transparency in their children's care is not well characterized. <h3>Objective</h3> To explore the preferences and experiences of parents of hospitalized children regarding the discussion and consideration of health care costs in the inpatient care of their children. <h3>Design, Setting, and Participants</h3> This cross-sectional multicenter survey study included 6 geographically diverse university-affiliated US children's hospitals from November 3, 2017, to November 8, 2018. Participants included a convenience sample of English- and Spanish-speaking parents of hospitalized children nearing hospital discharge. Data were analyzed from January 1, 2020, to June 25, 2021. <h3>Main Outcomes and Measures</h3> Parents' preferences and experiences regarding transparency of their child's health care costs. Multivariable linear regression examined associations between clinical and sociodemographic variables with parents' preferences for knowing, discussing, and considering costs in the clinical setting. Factors included family financial difficulties, child's level of chronic disease, insurance payer, deductible, family poverty level, race, ethnicity, parental educational level, and study site. <h3>Results</h3> Of 644 invited participants, 526 (82%) were enrolled (290 [55%] male), of whom 362 (69%) were White individuals, 400 (76%) were non-Hispanic/Latino individuals, and 274 (52%) had children with private insurance. Overall, 397 families (75%) wanted to discuss their child's medical costs, but only 36 (7%) reported having a cost conversation. If cost discussions were to occur, 294 families (56%) would prefer to speak to a financial counselor. Ninety-eight families (19%) worried discussing costs would hurt the quality of their child's care. Families with a medical financial burden unrelated to their hospitalized child had higher mean agreement that their child's physician should consider the family's costs in medical decision-making than families without a medical financial burden (effect size, 0.55 [95% CI, 0.18-0.92]). No variables were consistently associated with cost transparency preferences. <h3>Conclusions and Relevance</h3> Most parents want to discuss their child's costs during an acute hospitalization. Discussions of health care costs may be an important, relatively unexplored component of family-centered care. However, these discussions rarely occur, indicating a tremendous opportunity to engage and support families in this issue.
P05.01 Prospective validation trial of magnetic resonance imaging based Contrast Clearance Analysis (CCA) to differentiate between pseudoprogression/radiation necrosis and progressive disease following cranial radiotherapy
Authors: R Bodensohn, R Forbrig, S Lietke, J Reis, A Boulesteix, N L Albert, M Dorostkar, S Corradini, C Belka, N Thon, M Niyazi
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Pseudoprogression (PsP) or radiation necrosis (RN) may frequently occur after cranial radiotherapy and show a similar imaging pattern compared to progressive disease (PD). Even for experienced neuroradiologists, it remains challenging to distinguish between these clinically relevant disease states. We aimed to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) based Contrast Clearance Analysis (CCA) in this clinical setting. MATERIAL AND METHODS Patients with equivocal imaging findings after cranial radiotherapy were consecutively included into this monocentric prospective study. Assuming a true accuracy of 90% and setting the significance level to 0.05, N=33 patients are required to show that accuracy is larger than 70% with a power of 80% using a one-sided binomial test. CCA was performed by subtraction of imaging features in late vs early T1-weighted sequences after contrast-agent application. Two experienced neuroradiologists evaluated CCA with respect to PsP/RN and PD being blinded for FET PET and histological findings; histopathological diagnosis was based on stereotactic biopsy or resection for space-occupying processes. The radiological assessment was compared with the histopathological results, and its accuracy was calculated statistically. RESULTS Thirty-three patients were included; sixteen (48.5%) were treated because of a primary brain tumors, and 17 (51.1%) with brain metastases. In one patient, CCA was technically infeasible. The accuracy of CCA in predicting the histological result was 0.84 (95% CI 0.67–0.95; one-sided p=0.05; N=32). An accuracy of 0.85 (95% CI 0.68–0.95; one-sided p=0.04) would have been obtained in case of a correct classification in the non-analyzable case. Sensitivity and specificity of CCA were 0.93 (95%-CI 0.66–1.00) and 0.78 (95% CI 0.52–0.94), respectively. The accuracy in metastases patients was 0.94 (95% CI 0.71 - 1.00) and non-significantly higher compared to primary brain tumor patients with accuracy of 0.73 (95% CI 0.45 - 0.92), p=0.16. CONCLUSION In this study, CCA was a highly accurate, easy and helpful method for distinguishing PsP or RN from PD after cranial radiotherapy, especially in brain metastases patients after radiosurgical treatment.
Brigatinib Versus Crizotinib in ALK Inhibitor–Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial
Authors: D. Ross Camidge, Hye Ryun Kim, Myung-Ju Ahn, James C.H. Yang, Ji-Youn Han, Maximilian J. Hochmair, Ki Hyeong Lee, Angelo Delmonte, Maria Rosario Garcia Campelo, Dong-Wan Kim, Frank Griesinger, Enriqueta Felip, Raffaele Califano, Alexander I. Spira, Scott N. Gettinger, Marcello Tiseo, Huamao M. Lin, Yuyin Liu, Florin Vranceanu, Huifeng Niu, Pingkuan Zhang, Sanjay Popat
Journal: Journal of Thoracic Oncology (2021)

In the phase 3 study entitled ALK in Lung cancer Trial of brigAtinib in 1st Line (ALTA-1L), which is a study of brigatinib in ALK inhibitor-naive advanced ALK-positive NSCLC, brigatinib exhibited superior progression-free survival (PFS) versus crizotinib in the two planned interim analyses. Here, we report the final efficacy, safety, and exploratory results.Patients were randomized to brigatinib 180 mg once daily (7-d lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was a blinded independent review committee-assessed PFS. Genetic alterations in plasma cell-free DNA were assessed in relation to clinical efficacy.A total of 275 patients were enrolled (brigatinib, n = 137; crizotinib, n = 138). At study end, (brigatinib median follow-up = 40.4 mo), the 3-year PFS by blinded independent review committee was 43% (brigatinib) versus 19% (crizotinib; median = 24.0 versus 11.1 mo, hazard ratio [HR] = 0.48, 95% confidence interval [CI]: 0.35-0.66). The median overall survival was not reached in either group (HR = 0.81, 95% CI: 0.53-1.22). Posthoc analyses suggested an overall survival benefit for brigatinib in patients with baseline brain metastases (HR = 0.43, 95% CI: 0.21-0.89). Detectable baseline EML4-ALK fusion variant 3 and TP53 mutation in plasma were associated with poor PFS. Brigatinib exhibited superior efficacy compared with crizotinib regardless of EML4-ALK variant and TP53 mutation. Emerging secondary ALK mutations were rare in patients progressing on brigatinib. No new safety signals were observed.In the ALTA-1L final analysis, with longer follow-up, brigatinib continued to exhibit superior efficacy and tolerability versus crizotinib in patients with or without poor prognostic biomarkers. The suggested survival benefit with brigatinib in patients with brain metastases warrants future study.
Pediatric Acute Kidney Injury Survivors Need Risk Stratification and Individualized Follow-Up
Authors: Yuliang Zhao, Yajun Pu, Ling Zhang, Ping Fu
Journal: Journal of the American Society of Nephrology (2021)

We read with great interest "Long-term kidney outcomes following childhood acute kidney injury receiving dialysis: A population-based cohort study" by Robinson et al .[1][1] In this retrospective cohort study, 1699 pediatric survivors of dialysis-treated AKI were followed up for a median of 9.6
P11.01 Symptom networks in glioma: a novel approach to study multidimensional symptomatology in glioma patients
Authors: T M C K Varkevisser, J G Röttgering, P de Witt Hamer, M C M Kouwenhoven, J C Reijneveld, V Belgers, M van Lingen, M Klein, L Douw
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioma patients experience a high symptom burden contributing to poorer quality of life. Symptoms include depression, cognitive impairment, and fatigue and vary throughout the disease. These symptoms are rarely studied from a comprehensive perspective, while their interdependence may be relevant for their development, perpetuation, and ultimately successful treatment. The emerging field of symptom network analysis uncovers the multidimensional symptom space. Nodes are the symptoms, and edges are operationalized as the full conditional association, or partial correlation, between two symptom severity scores across patients. Highly connected nodes are considered central and may be particularly relevant targets for treatment as disruption of these central nodes impact the entire network. We visualized the overall glioma symptom network, compared multidimensional results to known literature, and statistically compared networks between relevant patient subgroups. MATERIAL AND METHODS A dataset comprised of 355 observations of 180 glioma patients at different disease phases was analysed. Cognitive testing and questionnaires regarding health-related and glioma-specific quality of life, fatigue, depression, and cognition resulted in the definition of 30 symptom nodes. Symptom clusters were visually explored in the resulting networks, as were node strength, betweenness, and closeness centrality measures for each node. Networks were statistically compared between preoperative patients and patients during stable disease, as well as patients with low versus high-grade gliomas. Networks of patients with normal versus severe levels of fatigue were also compared as cancer-/glioma-related fatigue has a strong impact on quality of life and can correlate with other common symptoms such as pain, depression, and/or sleep disturbance. RESULTS Symptom clusters existed between: 1) bodily pain, headache and physical functioning; 2) concentration and motivation; and 3) fatigue and drowsiness. Fatigue and mental health were the most central nodes in the networks. Furthermore, the overall connectivity between symptoms was significantly higher in the severely fatigued patients than in patients with normal fatigue. No network differences were found between low versus high-grade, and preoperative versus stable disease networks. CONCLUSION Fatigue is a central node in glioma patients’ burden of disease, and symptoms are more tightly intercorrelated in patients experiencing severe fatigue. From our data, we hypothesize that fatigue co-exists with or perpetuates other symptoms. Thus, although these results are preliminary, the network approach may innovate hypothesis generation in symptom management.
Allergic contact dermatitis caused by dipropylene glycol diacrylate in the Omnipod® insulin pump*
Authors: J. Ulriksdotter, C. Svedman, M. Bruze, M. Mowitz
Journal: British Journal of Dermatology (2021)

Cases of allergic contact dermatitis (ACD) caused by isobornyl acrylate (IBOA) in the Omnipod® insulin pump have previously been reported.To present three cases of patients with ACD caused by a new allergen in the pump, and results from chemical analyses.Omnipod pumps from different batches were analysed by gas chromatography-mass spectrometry. Aimed testing, with the department's medical device (MD) series and substances identified in the pump including dipropylene glycol diacrylate (DPGDA) at 0·01% and 0·1% in petrolatum (pet.), was performed. Patch testing also included extracts from the device, the adhesive patch as is, and allergens from baseline series.All patients tested positive to 0·1% DPGDA in pet., and two patients additionally to a 0·01% concentration. DPGDA was found in extracts of the Omnipod pumps brought by the patients. An Omnipod pump from an earlier batch contained tripropylene glycol diacrylate, IBOA, N,N-dimethylacrylamide, di(ethylene glycol)ethyl ether acrylate (DEGEA) but no DPGDA. One of the patients reacted positively to all of these allergens except DEGEA, which was not tested.When suspecting ACD to MDs, DPGDA at 0·1% in pet. should be tested. The contents of Omnipod have changed over time. Patch testing with updated test series and relevance assessment of positive reactions is a delicate task. Children, with lifelong use of MDs, risk contracting many allergies with potential cross-allergies. A question should be raised as to whether these low molecular weight acrylates should be used at all in devices constantly worn on the skin.