Cochrane corner: platinum-induced hearing loss after treatment for childhood cancer.

Related Articles

Cochrane corner: platinum-induced hearing loss after treatment for childhood cancer.

Int J Audiol. 2018 Dec 13;:1-4

Authors: Brennan-Jones CG, McMahen C, Van Dalen EC

Abstract
This Cochrane Corner features the review entitled "Platinum-induced hearing loss after treatment for childhood cancer" published in 2016. In their review, van As et al. identified 13 cohort studies including 2837 participants with a hearing test after treatment with a platinum-based therapy for different types of childhood cancers. All studies had problems related to quality of the evidence. The reported frequency of hearing loss varied between 1.7% and 90.1% for studies that included a definition of hearing loss; none of the studies provided data on tinnitus. Only two studies evaluated possible risk factors. One study found a higher risk of hearing loss in people treated with the combination of cisplatin plus carboplatin compared to treatment with cisplatin only and for exposure to aminoglycosides. The other found that age at treatment (lower risk in older children) and single maximum cisplatin dose (higher risk with an increasing dose) were significant predictors for hearing loss, while gender was not. This systematic review shows that children treated with platinum analogues are at risk of developing hearing loss, but the exact prevalence and risk factors remain unclear.

PMID: 30545270 [PubMed - as supplied by publisher]

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Cochrane corner: platinum-induced hearing loss after treatment for childhood cancer.

Related Articles

Cochrane corner: platinum-induced hearing loss after treatment for childhood cancer.

Int J Audiol. 2018 Dec 13;:1-4

Authors: Brennan-Jones CG, McMahen C, Van Dalen EC

Abstract
This Cochrane Corner features the review entitled "Platinum-induced hearing loss after treatment for childhood cancer" published in 2016. In their review, van As et al. identified 13 cohort studies including 2837 participants with a hearing test after treatment with a platinum-based therapy for different types of childhood cancers. All studies had problems related to quality of the evidence. The reported frequency of hearing loss varied between 1.7% and 90.1% for studies that included a definition of hearing loss; none of the studies provided data on tinnitus. Only two studies evaluated possible risk factors. One study found a higher risk of hearing loss in people treated with the combination of cisplatin plus carboplatin compared to treatment with cisplatin only and for exposure to aminoglycosides. The other found that age at treatment (lower risk in older children) and single maximum cisplatin dose (higher risk with an increasing dose) were significant predictors for hearing loss, while gender was not. This systematic review shows that children treated with platinum analogues are at risk of developing hearing loss, but the exact prevalence and risk factors remain unclear.

PMID: 30545270 [PubMed - as supplied by publisher]

from #Audiology via ola Kala on Inoreader https://ift.tt/2PC4laA
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Cochrane corner: platinum-induced hearing loss after treatment for childhood cancer.

Related Articles

Cochrane corner: platinum-induced hearing loss after treatment for childhood cancer.

Int J Audiol. 2018 Dec 13;:1-4

Authors: Brennan-Jones CG, McMahen C, Van Dalen EC

Abstract
This Cochrane Corner features the review entitled "Platinum-induced hearing loss after treatment for childhood cancer" published in 2016. In their review, van As et al. identified 13 cohort studies including 2837 participants with a hearing test after treatment with a platinum-based therapy for different types of childhood cancers. All studies had problems related to quality of the evidence. The reported frequency of hearing loss varied between 1.7% and 90.1% for studies that included a definition of hearing loss; none of the studies provided data on tinnitus. Only two studies evaluated possible risk factors. One study found a higher risk of hearing loss in people treated with the combination of cisplatin plus carboplatin compared to treatment with cisplatin only and for exposure to aminoglycosides. The other found that age at treatment (lower risk in older children) and single maximum cisplatin dose (higher risk with an increasing dose) were significant predictors for hearing loss, while gender was not. This systematic review shows that children treated with platinum analogues are at risk of developing hearing loss, but the exact prevalence and risk factors remain unclear.

PMID: 30545270 [PubMed - as supplied by publisher]

from #Audiology via ola Kala on Inoreader https://ift.tt/2PC4laA
via IFTTT

Pharmacokinetics of Prolonged-Release Once-Daily Formulations of Tacrolimus in De Novo Kidney Transplant Recipients: A Randomized, Parallel-Group, Open-Label, Multicenter Study

Abstract

Introduction

Different prolonged-release formulations of tacrolimus are available. To date, the pharmacokinetic (PK) profile of LCP-tacrolimus (LCPT; Envarsus^®) has not been compared with PR-Tac (Advagraf^®) in de novo kidney transplant recipients. These profiles will guide clinical recommendations for the initiation and dose titration strategies of once-daily tacrolimus formulations.

Methods

This randomized, parallel-group, open-label, multicenter PK study randomized 75 de novo, adult, white kidney transplant recipients to LCPT 0.17 mg/kg/day (n = 37) or PR-Tac 0.20 mg/kg/day (n = 38) for 4 weeks. Dose adjustments were permitted to target a pre-defined therapeutic range based on measured trough blood concentrations.

Results

PK analysis (days 1, 3, 7 and 14) included 68 patients (LCPT, n = 33; PR-Tac, n = 35). Similar proportions of patients were within the pre-defined therapeutic tacrolimus trough blood concentration range, with < 12% in each group having below-target trough levels over the study period. LCPT demonstrated ~ 30% greater relative bioavailability [LCPT/PR-Tac adjusted geometric mean ratio: day 3, 1.32 (p = 0.007); day 7, 1.25 (p = 0.051); day 14, 1.43 (p = 0.002)] and ~ 30% lower peak-to-trough percentage fluctuation of blood concentration [LCPT/PR-Tac adjusted geometric mean ratio: day 3, 0.70 (p < 0.001); day 7, 0.68 (p < 0.001); day 14, 0.73 (p = 0.004)] in addition to longer time to maximum blood concentration (t_max), lower maximum concentration (C_max) and a consistently lower daily dose (~ 40% dose reduction with LCPT vs. PR-Tac by day 28). Safety profiles were similar.

Conclusion

In de novo kidney transplant recipients, prolonged-release formulations of tacrolimus can reach therapeutic concentrations in the immediate post-transplant period. LCPT has greater relative bioavailability and lower peak-to-trough fluctuation compared with PR-Tac.

Trial registration

Registered at ClinicalTrials.gov; study number NCT02500212.

Funding

Chiesi Farmaceutici S.p.A.

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From deep learning to transfer learning for the prediction of skeletal muscle forces

Abstract

Skeletal muscle forces may be estimated using rigid musculoskeletal models and neural networks. Neural network (NN) approach has the advantages of real-time estimation ability and promising prediction accuracy. However, most of the developed NN models are based on conventional feedforward NNs, which do not take dynamic temporal relationships of the muscle force profiles into consideration. The objectives of this present paper are twofold: (1) to develop a recurrent deep neural network (RDNN) incorporating dynamic temporal relationships to estimate skeletal muscle forces from kinematics data during a gait cycle; (2) then to establish a transfer learning strategy to improve the accuracy of muscle force estimation. A long short-term memory (LSTM) model as a RDNN was developed and evaluated. A weight transfer strategy was established. Three databases were established for training and evaluation purposes. The predictions of rectus femoris, soleus, and tibialis anterior forces with developed LSTM network show root mean square error range of 2.4–84.6 N. Relative root mean square error (RMSE) deviations for internal and external validations are less than 5% and 10% for all analyzed muscles respectively. Pearson correlation coefficients (R) range of 0.95–0.999 showed perfect waveform similarity between data and predicted muscle forces for all analyzed muscles. The use of weight transfer leads to an improvement of 1.3% for the relative deviation between simulation outcome and LSMT prediction. This present study suggests that the recurrent deep neural network is a powerful and accurate computational tool for the prediction of skeletal muscle forces. Moreover, the coupling between this deep learning approach and a transfer learning strategy leads to improve the prediction accuracy. In future work, this coupling approach will be incorporated into a developed decision support tool for functional rehabilitation with real-time estimation and tracking of skeletal muscle forces.

Graphical abstract

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M1/M2 Macrophages Play Different Roles in Adipogenic Differentiation of PDGFRα + Preadipocytes In Vitro

Abstract

Background

PGGFRα⁺ preadipocytes are the major subpopulations that can regenerate into adipocytes. Two different types of macrophages exist in the fat tissue: the classically activated macrophage (M1) and the alternatively activated macrophage (M2). In this study, we investigated whether M1/M2 macrophages play distinct roles in adipogenic differentiation of PDGFRα⁺ preadipocytes.

Methods

Mouse preadipocytes and macrophages were isolated from C57BL/6 male mice of 6–8 weeks. The culture supernate of M1 and M2 macrophages was collected and co-cultured with the PDGFRα⁺ preadipocytes. After 3 days, Oil Red O staining was used to evaluate to adipogenic differentiation of PDGFRα⁺ preadipocytes and the expression of adipogenic-related transcription factors (C/EBP-α, PPARγ) were also tested.

Results

The results showed that when cultured in vitro, M1 macrophages could significantly suppress the adipogenesis of PDGFRα⁺ preadipocytes as well as the C/EBP-α and PPARγ expression, but M2 macrophages did not have significant influence on the adipogenesis of PDGFRα⁺ preadipocytes nor on C/EBP-α and PPARγ expression compared with the control group.

Conclusions

M1 macrophages significantly suppress PDGFRα⁺ preadipocyte adipogenesis which provides a possible way to improve adipogenesis and fat retention after fat-free grafting by mitigating acute inflammation and manipulating M1 macrophage levels.

No Level Assigned

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

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Editorial and Review: 33 rd Asilomar Conference on Mass Spectrometry—Impact of Metabolomics in Translational and Clinical Research

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