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Purpose Age, MYCN status, stage, and histology have been used as neuroblastoma (NB) risk factors for decades. Serum lactate dehydrogenase (LDH) and serum ferritin are reproducible, easily obtained, and prognostic, though never used in risk stratification, except one German trial. We analyzed the prognostic strength of LDH and ferritin, overall, within high-risk NB, and by era, using the International Neuroblastoma Risk Group Data Commons. Patients and methods Children with NB (1990-2016) were categorized into LDH (n = 8867) and ferritin (n = 8575) risk groups using EFS. Cox models compared the prognostic strength of LDH and ferritin to age, MYCN status, and INSS stage. Results Higher LDH conferred worse EFS, overall (5-year EFS) (100-899 IU/L 76 ± 0.6%; 0-99 or 900-1399 IU/L 60 ± 1.2%; ≥1400 IU/L 36 ± 1.2%; P less then .0001), and in high-risk NB post-2009 (3-year EFS) (117-381 IU/L 67 ± 8.9%; 382-1334 IU/L 58 ± 4.4%; 0-116 or ≥1335 IU/L 46 ± 3.9%; P = .003). Higher ferritin conferred worse EFS, overall (5-year EFS) (1-29 ng/mL 87 ± 0.9%; 0 or 30-89 ng/mL 74 ± 0.8%; ≥90 ng/mL 48 ± 0.9%; P less then .0001), and in high-risk NB post-2009 (3-year EFS) (1-53 ng/mL 71 ± 9.3%; 0 or 54-354 ng/mL 55 ± 4.7%; ≥355 ng/mL 34 ± 6.1%; P = .0008). In multivariable analyses adjusting for age, MYCN, and stage, LDH and ferritin maintained independent prognostic ability (P less then .0001; adjusted HRs (95% CI) 1.7 (1.5-1.9), 2.3 (2.0-2.7), respectively). Conclusions LDH and ferritin are strongly prognostic in NB, overall and within high-risk NB patients treated post-2009 with modern therapy. LDH and ferritin show promise for (a) identifying ultra-high-risk; (b) refining risk stratification; and (c) clinical utility in low-/middle-income countries. Routine collection of LDH and ferritin should be reinitiated for evolving NB risk stratification.The novel coronavirus SARS-CoV-2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. https://www.selleckchem.com/Proteasome.html One area of active inquiry is understanding the mode(s) of SARS-CoV-2 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS-CoV-2) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on 17 April 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS-CoV in human milk (it was negative); and no published data on MERS-CoV and human milk. We identified 13 studies reporting human milk tested for SARS-CoV-2; one study (a non-peer-reviewed preprint) detected the virus in one milk sample, and another study detected SARS-CoV-2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS-CoV-2) during breastfeeding are discussed.Background Subtyping chronic rhinosinusitis (CRS) by tissue eosinophilia has prognostic and therapeutic implications, and is difficult to predict using peripheral eosinophil counts or polyp status alone. The objective of this study was to test machine learning for prediction of eosinophilic CRS (eCRS). Methods Input variables were defined as peripheral eosinophil count, urinary leukotriene E4 (uLTE4) level, and polyp status. The output was diagnosis of eCRS, defined as tissue eosinophil count >10 per high-power field. Patients undergoing surgery for CRS were retrospectively reviewed for complete datasets. Univariate analysis was performed for each input as a predictor of eCRS. Logistic regression and artificial neural network (ANN) machine learning models were developed using random and surgeon specific training/test datasets. Results A total of 80 patients met inclusion criteria. In univariate analysis, area under the curve (AUC) for peripheral eosinophil count and uLTE4 were 0.738 (95% confidence interval, 0.616-0.840) and 0.728 (0.605-0.822), respectively. Presence of polyps was 94.1% sensitive, but 51.7% specific. Logistic regression models using random and surgeon specific datasets resulted in AUC of 0.882 (0.665-0.970) and 0.945 (0.755-0.995) respectively. ANN models resulted in AUC of 0.918 (0.756-0.975) and 0.956 (0.828-0.999) using random and surgeon specific datasets, respectively. Model comparison of logistic regression and ANN was not statistically different. All machine learning models had AUC greater than univariate analyses (all p less then 0.003) CONCLUSIONS Machine learning of three clinical inputs has the potential to predict eCRS with high sensitivity and specificity in this patient population. Prospective investigation using larger and more diverse populations is warranted. This article is protected by copyright. All rights reserved.NEPA is the only fixed combination antiemetic, comprised of an NK1 RA (netupitant) and a 5-HT3 RA (palonosetron). In the first head-to-head trial to compare NK1 RA-containing regimens, a single oral dose of NEPA was non-inferior to a 3-day aprepitant/granisetron (APR/GRAN) regimen for the primary endpoint of overall (0-120 hours) complete response (no emesis/no rescue). This pre-specified analysis evaluates the efficacy of NEPA versus APR/GRAN in the subset of Chinese patients in the study. In addition, efficacy in patients at greatest emetic risk receiving high-dose cisplatin (≥70 mg/m2 ) was explored. Chemotherapy-naïve patients with solid tumors in this randomized, double-blind study received either a single dose of NEPA prior to cisplatin-based chemotherapy or a 3-day regimen of APR/GRAN, both with dexamethasone on Days 1-4. Efficacy was evaluated through complete response, no emesis, and no significant nausea rates during the acute (0-24 hours), delayed (25-120 hours) and overall phases as well as individual days post-chemotherapy, as the daily course of CINV protection is often unstudied.
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