tbuckley/cabot-search huggingface dataset:
Abstract 185: Is Lymph-Node-First Kawasaki Disease a High-risk Group for Coronary Aneurysm?
Authors: Jeng-Sheng Chang, Yu-Chih Huang
Journal: Circulation (2015)

Cervical lymphadenopathy (CLA) is the least common main feature in patients with Kawasaki disease (KD), comprising only 42%-65% of all diagnoses. Nonetheless, several studies have shown that KD patients who first present with remarkable CLA and fever (NF-KD) are older in age and exhibit stronger inflammation than that of typical KD (tKD) patients. Therefore, whether NF-KD patients are also a high-risk group for intravenous immunoglobulin resistance (rIVIG) and coronary arterial aneurysm (CAA), and whether tKD with CLA (tKD-CLA) is associated with higher inflammatory indices than tKD without CLA warrants investigation. Previous retrospective (R) and prospective (P) studies have shown varied results (Table). In this study, we reviewed 10 years of medical records from a tertiary referral hospital and identified 42 NF-KD patients. These NF-KD patients were then compared with 113 tKD-CLA and 105 tKD patients from the same database over the same period. Significant trends of increasing values were noted in age, neutrophils, CRP, ESR, GOT, and doses of IVIG among these 3 groups of patients ( p = 0.03 to &lt; 0.0001). NF-KD patients presented with larger cervical LN (3.7 ± 7.0 cm) complicated by higher CAA (12/42 vs. 25/218, p = 0.008) and by moderate to extremely high CAA (6/42 vs. 4/218, p = 0.002), and suffered more CHF or shock at the acute stage (6/42 vs. 6/218, p &lt; 0.001) than all of the tKD patients. The size of LN did not correlate with CAA occurrence, but the presence of bilateral CLA showed a higher risk for CAA than unilateral CLA did (6/10 vs. 6/32, p = 0.02). Author(Hospital No.) Method NF-KD tKD-CLA tKD LN(cm) CAA rIVIG Nomura Y (1) R 16 106 65 &gt; 1.5 + + Kanegaye JT (1) P 53 . 287 3.0 ± 1.0 - - Kubota M (1) R 29 62 107 &gt; 1.5 - - Sung RYT (14) R . 170 526 &gt; 1.5 - - Chang JS (1) R 42 113 105 3.7 ± 7.0 + + This study showed that NF-KD patients, particularly those with larger lymph nodes, are a high risk group for CAA complications. The tKD-CLA patients also exhibited a tendency for higher inflammation. Previous pathological studies of swollen CLA have reported tissue edema in the sinus and paracortical areas of LN, as well as vessel thrombi in severe cases. Further study of swollen CLA is warranted to determine the pathological correlation between CLA severity and CAA complications in KD patients.
Identifying gaps in global health dermatology: a survey of GLODERM members
Authors: D.E. McMahon, L. Oyesiku, E. Amerson, H. Beltraminelli, A.Y. Chang, A. Forrestel, R. Hay, A. Knapp, C. Kovarik, T. Maurer, S.A. Norton, W. Rehmus, C. Van Hees, K.A. Wanat, V.L. Williams, L.C. Fuller, E.E. Freeman
Journal: British Journal of Dermatology (2021)

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Preventive psychiatry: a blueprint for improving the mental health of young people
Authors: Paolo Fusar‐Poli, Christoph U. Correll, Celso Arango, Michael Berk, Vikram Patel, John P.A. Ioannidis
Journal: World Psychiatry (2021)

Preventive approaches have latterly gained traction for improving mental health in young people. In this paper, we first appraise the conceptual foundations of preventive psychiatry, encompassing the public health, Gordon's, US Institute of Medicine, World Health Organization, and good mental health frameworks, and neurodevelopmentally-sensitive clinical staging models. We then review the evidence supporting primary prevention of psychotic, bipolar and common mental disorders and promotion of good mental health as potential transformative strategies to reduce the incidence of these disorders in young people. Within indicated approaches, the clinical high-risk for psychosis paradigm has received the most empirical validation, while clinical high-risk states for bipolar and common mental disorders are increasingly becoming a focus of attention. Selective approaches have mostly targeted familial vulnerability and non-genetic risk exposures. Selective screening and psychological/psychoeducational interventions in vulnerable subgroups may improve anxiety/depressive symptoms, but their efficacy in reducing the incidence of psychotic/bipolar/common mental disorders is unproven. Selective physical exercise may reduce the incidence of anxiety disorders. Universal psychological/psychoeducational interventions may improve anxiety symptoms but not prevent depressive/anxiety disorders, while universal physical exercise may reduce the incidence of anxiety disorders. Universal public health approaches targeting school climate or social determinants (demographic, economic, neighbourhood, environmental, social/cultural) of mental disorders hold the greatest potential for reducing the risk profile of the population as a whole. The approach to promotion of good mental health is currently fragmented. We leverage the knowledge gained from the review to develop a blueprint for future research and practice of preventive psychiatry in young people: integrating universal and targeted frameworks; advancing multivariable, transdiagnostic, multi-endpoint epidemiological knowledge; synergically preventing common and infrequent mental disorders; preventing physical and mental health burden together; implementing stratified/personalized prognosis; establishing evidence-based preventive interventions; developing an ethical framework, improving prevention through education/training; consolidating the cost-effectiveness of preventive psychiatry; and decreasing inequalities. These goals can only be achieved through an urgent individual, societal, and global level response, which promotes a vigorous collaboration across scientific, health care, societal and governmental sectors for implementing preventive psychiatry, as much is at stake for young people with or at risk for emerging mental disorders.
Silk-elastinlike copolymers enhance bioaccumulation of semisynthetic glycosaminoglycan ethers for prevention of radiation induced proctitis
Authors: D. Steinhauff, M. Jensen, M. Talbot, W. Jia, K. Isaacson, J. Jedrzkiewicz, J. Cappello, S. Oottamasathien, H. Ghandehari
Journal: Journal of Controlled Release (2021)
Association of the neutrophil to eosinophil ratio with response to immunotherapy-based combinations in metastatic renal cell carcinoma.
Authors: Matthew D Tucker, Katy Beckermann, Kristin Kathleen Ancell, Kerry Schaffer, Renee McAlister, Deborah Wallace, Elizabeth Kaiser, Nancy B. Davis, W. Kimryn Rathmell, Brian I. Rini
Journal: Journal of Clinical Oncology (2021)

341 Background: Neutrophilia is known to be associated with worse prognosis in metastatic renal cell carcinoma (mRCC); however, less is known about the role of eosinophils in the response to immunotherapy (IO). We investigated the association of the baseline neutrophil to eosinophil ratio (NER) with outcomes to IO-based combination treatment in mRCC. Methods: Patients with mRCC treated with ipilimumab plus nivolumab, pembrolizumab plus axitinib, or avelumab plus axitinib at the Vanderbilt-Ingram Cancer Center were retrospectively identified. Patients on &gt;10mg prednisone and patients with prior IO were excluded. Baseline NER (at time of first IO) and association with progression free survival (PFS), overall survival (OS), and objective response rate (ORR) were investigated. Data cutoff was 9/1/2020. Analysis for PFS and OS was performed using the log-rank test and Mantel-Haenszel method, and analysis of the odds ratio for ORR was performed using Fischer’s exact test. Results: Sixty-one patients were identified: 89% clear cell histology, 74% prior nephrectomy, 69% IMDC intermediate risk, and 72% treatment-naïve. Patients with baseline NER &lt; median (N=31) had improved clinical outcomes compared to patients with baseline NER &gt; median (N=30) (Table). Improvement in PFS by NER was maintained when stratified by anti-PD-1/CTLA-4 and anti-PD(L)-1/VEGF (p= 0.0062 and p= 0.049); however, differences in OS and ORR were no longer significant. The median baseline NER among patients with partial response (PR) was significantly lower at 22.7 (95% CI 18.9-31.1) vs. 51.6 (95% CI 39.5-93.1) among those with progressive disease (PD) (p= 0.0054). For comparison, the median neutrophil to lymphocyte ratio was not significantly different between PR (2.60) and PD (3.84, p= 0.056). Conclusions: Patients with a low baseline NER treated with IO-based combinations had improved clinical outcomes compared to patients with a high baseline NER. Additional investigation of this parameter in larger cohorts is warranted. [Table: see text]
Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?
Authors: Marco Volante, Ozgur Mete, Giuseppe Pelosi, Anja C. Roden, Ernst Jan M. Speel, Silvia Uccella
Journal: Endocrine Pathology (2021)

Abstract Thoracic (pulmonary and thymic) neuroendocrine tumors are well-differentiated epithelial neuroendocrine neoplasms that are classified into typical and atypical carcinoid tumors based on mitotic index cut offs and presence or absence of necrosis. This classification scheme is of great prognostic value but designed for surgical specimens, only. Deep molecular characterization of thoracic neuroendocrine tumors highlighted their difference with neuroendocrine carcinomas. Neuroendocrine tumors of the lung are characterized by a low mutational burden, and a high prevalence of mutations in chromatin remodeling and histone modification-related genes, whereas mutations in genes frequently altered in neuroendocrine carcinomas are rare. Molecular profiling divided thymic neuroendocrine tumors into three clusters with distinct clinical outcomes and characterized by a different average of copy number instability. Moreover, integrated histopathological, molecular and clinical evidence supports the existence of a grey zone category between neuroendocrine tumors (carcinoid tumors) and neuroendocrine carcinomas. Indeed, cases with well differentiated morphology but mitotic/Ki-67 indexes close to neuroendocrine carcinomas have been increasingly recognized. These are characterized by specific molecular profiles and have an aggressive clinical behavior. Finally, thoracic neuroendocrine tumors may arise in the background of genetic susceptibility, being MEN1 syndrome the well-defined familial form. However, pathologists should be aware of rarer germline variants that are associated with the concurrence of neuroendocrine tumors of the lung or their precursors (such as DIPNECH) with other neoplasms, including but not limited to breast carcinomas. Therefore, genetic counseling for all young patients with thoracic neuroendocrine neoplasia and/or any patient with pathological evidence of neuroendocrine cell hyperplasia-to-neoplasia progression sequence or multifocal disease should be considered.
“Double trouble”: embedded lumen-apposing metal stent and embolization coils
Authors: Amandeep Singh, Farhan Qayyum, Prabhleen Chahal
Journal: Endoscopy (2021)

A 56-year-old man with history of alcoholic pancreatitis complicated by chronic pseudocyst in the pancreatic head presented with abdominal pain and enlarging pseudocyst. He underwent endoscopic ultrasound-guided cystogastrostomy and placement of an AXIOS 15 × 10 mm lumen-apposing metal stent (LAMS; Boston Scientific, Marlborough, Massachusetts, USA). He presented at the emergency department 2 weeks later with melena and a 4-g drop in hemoglobin. Computed tomography angiogram followed by visceral angiogram confirmed inferior pancreaticoduodenal artery (PDA) pseudoaneurysm, which was treated with coil embolization ([Fig. 1], [Fig. 2]). No further episodes of melena occurred and the patient was discharged in a stable condition.
Abstract 12890: Latent Cluster Analysis Using Clinical and Functional Characteristics Identifies Novel Phenotypes of Patients With Reduced Ejection Fraction Enrolled in the HF-ACTION Trial With Differential Association With Mortality
Authors: Bethany Doran, Christophe Roeder, Miranda Merrill, Pardeep Jhund, Laura Stevens, John McMurray, Carsten Görg, David P Kao
Journal: Circulation (2018)

Introduction: Patients with heart failure with reduced ejection fraction (HFrEF) are phenotypically heterogeneous, and functional status and prognosis associated with complex phenotypes are poorly ...
Managing Patients With Short-Term Mechanical Circulatory Support
Authors: Tim Balthazar, Christophe Vandenbriele, Frederik H. Verbrugge, Corstiaan Den Uil, Annemarie Engström, Stefan Janssens, Steffen Rex, Bart Meyns, Nicolas Van Mieghem, Susanna Price, Tom Adriaenssens
Journal: Journal of the American College of Cardiology (2021)
Towards personalised management for non-variceal upper gastrointestinal bleeding
Authors: Joseph J Y Sung, Loren Laine, Ernst J Kuipers, Alan N Barkun
Journal: Gut (2021)

Guidelines from national and international professional societies on upper gastrointestinal bleeding highlight the important clinical issues but do not always identify specific management strategies pertaining to individual patients. Optimal treatment should consider the personal needs of an individual patient and the pertinent resources and experience available at the point of care. This article integrates international guidelines and consensus into three stages of management: pre-endoscopic assessment and treatment, endoscopic evaluation and haemostasis and postendoscopic management. We emphasise the need for personalised management strategies based on patient characteristics, nature of bleeding lesions and the clinical setting including available resources.
OTS167 blocks FLT3 translation and synergizes with FLT3 inhibitors in FLT3 mutant acute myeloid leukemia
Authors: Bartholomew J. Eisfelder, Caner Saygin, Joseph Wynne, Margaret W. Colton, Mariafausta Fischietti, Elspeth M. Beauchamp, Jason X. Cheng, Olatoyosi Odenike, Gail Roboz, Houda Alachkar, Wendy Stock
Journal: Blood Cancer Journal (2021)

Abstract Internal tandem duplication (-ITD) mutations of Fms-like tyrosine kinase 3 (FLT3) provide growth and pro-survival signals in the context of established driver mutations in FLT3 mutant acute myeloid leukemia (AML). Maternal embryonic leucine zipper kinase (MELK) is an aberrantly expressed gene identified as a target in AML. The MELK inhibitor OTS167 induces cell death in AML including cells with FLT3 mutations, yet the role of MELK and mechanisms of OTS167 function are not understood. OTS167 alone or in combination with tyrosine kinase inhibitors (TKIs) were used to investigate the effect of OTS167 on FLT3 signaling and expression in human FLT3 mutant AML cell lines and primary cells. We describe a mechanism whereby OTS167 blocks FLT3 expression by blocking FLT3 translation and inhibiting phosphorylation of eukaryotic initiation factor 4E–binding protein 1 (4E-BP1) and eukaryotic translation initiation factor 4B (eIF4B). OTS167 in combination with TKIs results in synergistic induction of FLT3 mutant cell death in FLT3 mutant cell lines and prolonged survival in a FLT3 mutant AML xenograft mouse model. Our findings suggest signaling through MELK is necessary for the translation and expression of FLT3-ITD, and blocking MELK with OTS167 represents a viable therapeutic strategy for patients with FLT3 mutant AML.
Discovery of synergistic material-topography combinations to achieve immunomodulatory osteoinductive biomaterials using a novel in vitro screening method: The ChemoTopoChip
Authors: Laurence Burroughs, Mahetab H. Amer, Matthew Vassey, Britta Koch, Grazziela P. Figueredo, Blessing Mukonoweshuro, Paulius Mikulskis, Aliaksei Vasilevich, Steven Vermeulen, Ian L. Dryden, David A. Winkler, Amir M. Ghaemmaghami, Felicity R.A.J. Rose, Jan de Boer, Morgan R. Alexander
Journal: Biomaterials (2021)

Human mesenchymal stem cells (hMSCs) are widely represented in regenerative medicine clinical strategies due to their compatibility with autologous implantation. Effective bone regeneration involves crosstalk between macrophages and hMSCs, with macrophages playing a key role in the recruitment and differentiation of hMSCs. However, engineered biomaterials able to simultaneously direct hMSC fate and modulate macrophage phenotype have not yet been identified. A novel combinatorial chemistry-topography screening platform, the ChemoTopoChip, is used here to identify materials suitable for bone regeneration by screening 1008 combinations in each experiment for human immortalized mesenchymal stem cell (hiMSCs) and human macrophage response. The osteoinduction achieved in hiMSCs cultured on the "hit" materials in basal media is comparable to that seen when cells are cultured in osteogenic media, illustrating that these materials offer a materials-induced alternative to osteo-inductive supplements in bone-regeneration. Some of these same chemistry-microtopography combinations also exhibit immunomodulatory stimuli, polarizing macrophages towards a pro-healing phenotype. Maximum control of cell response is achieved when both chemistry and topography are recruited to instruct the required cell phenotype, combining synergistically. The large combinatorial library allows us for the first time to probe the relative cell-instructive roles of microtopography and material chemistry which we find to provide similar ranges of cell modulation for both cues. Machine learning is used to generate structure-activity relationships that identify key chemical and topographical features enhancing the response of both cell types, providing a basis for a better understanding of cell response to micro topographically patterned polymers.
Inferior Colliculus’s Hypermetabolism
Authors: Agathe Chammas, Izzie Jacques Namer, François Lersy, Stéphane Kremer, Caroline Bund
Journal: Clinical Nuclear Medicine (2021)

Abstract We present the case of a 64-year-old man presenting an episode of confusion during SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection with a positive oropharyngeal swab polymerase chain reaction test. He was hospitalized for dyspnea related to pneumonia demonstrated on chest CT. FDG PET performed after the confusion phase, but still in the COVID-19 (coronavirus disease 2019)–positive phase, showed high glucose metabolism of the inferior colliculi. Morphological MRI was normal. The first-pass perfusion MRI shows hyperperfusion of the inferior colliculi, corresponding to FDG PET hypermetabolism.
Clinical outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) receiving radium-223 (Ra-223) early versus late in the treatment sequence.
Authors: Lawrence Mbuagbaw, Jennifer Lowther, Richard M. Lee-Ying
Journal: Journal of Clinical Oncology (2021)

136 Background: Ra-223 is the only targeted alpha therapy shown to prolong overall survival (OS) in men with mCRPC. The purpose of this real-world study is to evaluate clinical outcomes of patients (pts) when Ra-223 is used early (second-line) or late (third or later lines) for mCRPC. Methods: We used administrative databases in Ontario (2012-2017) to estimate OS from start of second-line life prolonging therapy (LPT), event free survival (EFS; time from start of second-line LPT to start of fourth-line or death) using counting process models, comparing 2 cohorts of patients: Early Ra-223 (2nd line) vs Late Ra-223 (3rd or later line). All models are adjusted for relevant fixed and time-varying covariates, including age, prostate specific antigen, hemoglobin, Charlson Comorbidity Index (CCI), use of bone health agents, prior systemic treatments, Gleason score, TNM score, Androgen Deprivation Therapy (ADT) and standardized pain score. Results: Data from 598 men in Ontario with mCRPC who received at least 2 lines of LPT, including Ra-223 in second line or later were analyzed (Early Ra-223=253; 42.3%; Late Ra-223=345; 57.7%). The mean age (standard deviation) at the start of first-line LPT was 72.2 years (8.8). Patients in the early Ra-223 cohort had a longer time from diagnosis of prostate cancer to receiving first-line LPT, a longer time from start of first-line to start of second-line LPT, and were less likely to receive docetaxel. The median number of Ra-223 cycles was 5 (range 3-6) and 4 (range 3-6) and the mean number lines of total LPT was 2.7 ± 0.9 (2.0 - 7.0) and 3.8 ± 0.9 (3.0 - 7.0) in the early and late Ra-223 cohorts, respectively. OS was better in the Early Ra-223 cohort compared to the Late Ra-223 cohort (Hazard Ratio [HR] 0.79; 95% Confidence Interval [CI] 0.66-0.95). EFS was better in the Early Ra-223 cohort compared to the Late Ra-223 cohort (HR 0.71; 95% CI 0.58-0.86). Time to first hospitalization and time to first emergency department visit was longer in the early Ra-223 cohort. Conclusions: Real-world data from Ontario, suggests that patients who received Ra-223 in second-line versus third-line or later had better outcomes. Patients who received Ra-223 early received less chemotherapy, but had better survival. The selection of patients who may benefit the most from Ra-223, and the optimal timing of the Ra-223 in the sequence of treatments, are being evaluated in a larger Canadian study including data from four Canadian provinces (REACTIVATE NCT04281147 ).
Outcomes of older men receiving docetaxel for metastatic hormone-sensitive prostate cancer.
Authors: Daniel E Lage, M Dror Michaelson, Richard J. Lee, Joseph A. Greer, Jennifer S. Temel, Christopher Sweeney
Journal: Journal of Clinical Oncology (2021)

82 Background: Most men who die of prostate cancer are older than 70 years, and the impact of therapy in this population is poorly defined. The ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) randomized men of all ages with metastatic hormone-sensitive prostate cancer (mHSPC) to receive androgen deprivation therapy (ADT) with or without docetaxel. Methods: The results of CHAARTED showed an overall survival (OS) benefit for the addition of docetaxel to ADT in men with mHSPC. In a secondary analysis of this trial, we assessed patient characteristics and OS in patients ≥70 years (“older men”) versus &lt;70 years (“younger men”) with Cox proportional hazards models. Additionally, we compared adverse events, therapy completion rate, and subsequent treatment patterns between these two groups using Chi-squared tests. Results: Of the 790 patients enrolled, 177 (22.4%) were ≥70 years. A greater proportion of older men had an impaired performance status (Eastern Cooperative Oncology Group 1-2: 36.7% vs. 28.6%, p=0.038) and prior local therapy (31.7% vs. 25.9%, p&lt;0.001) compared to younger men. Docetaxel + ADT resulted in improved OS in both older and younger men (Hazard Ratio [HR] 0.45, 95%CI: 0.25-0.80 for older men; HR 0.71, 95%CI: 0.53-0.95 for younger men). This treatment benefit was seen for subgroups of older men with high volume disease (HR 0.43, 95%CI 0.23-0.79) and de novo metastatic disease (HR 0.36, 95%CI 0.19-0.69). A similar proportion of older and younger men completed all six cycles of docetaxel (82.6% vs. 87.1%, p=0.28). Rates of grade 3-5 adverse events were similar between older and younger men (36.8% of older men vs. 26.8% of younger men, p=0.69). The rate of any Grade 4-5 adverse events did not differ significantly between older and younger men (14.9% vs. 11.9%, respectively, p=0.46). In the control arm, a smaller proportion of older men received subsequent cancer treatments (34.4% vs. 51.5%, p=0.017) or subsequent docetaxel (25.6% vs. 37.6%, p=0.035) compared to younger men. Conclusions: In summary, older men with mHSPC who were eligible to participate in a clinical trial had similar OS benefit and clinical outcomes compared to younger men when receiving docetaxel chemotherapy + ADT. Oncologists should consider docetaxel chemotherapy as a favorable treatment option for older men with mHSPC who are fit for chemotherapy. Clinical trial information: NCT00309985.