Randomized controlled trial on the effect of 1-hour infusion of vincristine versus push injection on neuropathy in children with cancer (final analysis)

Introduction: Vincristine is an integral component of treatment for children with cancer. Its main dose-limiting side effect is vincristine-induced peripheral neuropathy (VIPN). The VINCA trial was a randomized controlled trial that explored the effect of 1-hour infusion compared with push injection of vincristine on the development of VIPN in children with cancer. The short-term outcomes (median follow-up 9 months) showed that there was no difference in VIPN between the randomization groups. However, 1-hour infusion was less toxic in children who also received azoles. We now report the results of the final analyses (median follow-up 20 months), which includes treatment outcome as a secondary objective (follow-up 3 years). Methods: VIPN was measured 1–7 times per participant using the Common Terminology Criteria for Adverse Events (CTCAE) and the pediatric-modified total neuropathy score. Poisson mixed model and logistic generalized estimating equation analysis for repeated measures were performed.Results: Forty-five participants per randomization group were included. There was no significant effect of 1-hour infusion compared with push injection on VIPN. In participants receiving concurrent azoles, the total CTCAE score was significantly lower in the one-hour group (rate ratio 0.52, 95% confidence interval 0.33–0.80, p = 0.003). Four patients in the one-hour group and one patient in the push group relapsed. Two patients in the one-hour group died. Conclusion:1-hour infusion of vincristine is not protective against VIPN. However, in patients receiving concurrent azoles, 1-hour infusion may be less toxic. The difference in treatment outcome is most likely the result of differences in risk profile.</p

Central venous catheter–associated complications in pediatric patients diagnosed with Hodgkin lymphoma: implications for catheter choice

Purpose The purpose of this study was to determine the most optimal central venous catheter (CVC) for pediatric patients with Hodgkin lymphoma (HL) in terms of complications.Methods A retrospective study including patients diagnosed with HL from 2015 to 2021 at the Princess Maxima Center was performed. Patients were followed from CVC insertion until removal or 06-2021, whichever came first. The primary outcome was the CVC-related complication incidence rate (IR) per 1000 CVC-days. Furthermore, the incidence rate ratio (IRR) was calculated by comparing complication IRs between peripherally inserted central catheters (PICC) and totally implantable venous access ports (TIVAP). Additionally, risk factors for central venous thrombosis (CVT) were identified.Results A total of 98 patients were included. The most frequently observed complications were local irritation/infections (18%; IR 0.93), malfunctions (15%; IR 0.88), and CVC-related CVTs (10%; IR 0.52). Single lumen PICCs were associated with a higher risk of complications (49% vs. 26%; IRR 5.12, CI95% 2.76-9.50), severe complications (19% vs. 7%; IRR 11.96, CI95% 2.68-53.42), and early removal (18% vs. 7%; IRR 9.96, CI95% 2.18-45.47). A single lumen PICC was identified as a risk factor for CVC-related CVT when compared to TIVAPs (12% vs. 7%, IRR 6.98, CI95% 1.45-33.57).Conclusion The insertion of a TIVAP rather than a PICC should be recommended for pediatric patients with HL, especially in the presence of CVT-related risk factors. Future trials should evaluate the efficacy and safety of direct oral anticoagulants for the primary prevention of CVT in pediatric patients with a PICC and other CVT-related risk factors.Analysis and Stochastic

Consensus molecular subtype classification of colorectal adenomas

Consensus molecular subtyping is an RNA expression-based classification system for colorectal cancer (CRC). Genomic alterations accumulate during CRC pathogenesis, including the premalignant adenoma stage, leading to changes in RNA expression. Only a minority of adenomas progress to malignancies, a transition that is associated with specific DNA copy number aberrations or microsatellite instability (MSI). We aimed to investigate whether colorectal adenomas can already be stratified into consensus molecular subtype (CMS) classes, and whether specific CMS classes are related to the presence of specific DNA copy number aberrations associated with progression to malignancy. RNA sequencing was performed on 62 adenomas and 59 CRCs. MSI status was determined with polymerase chain reaction-based methodology. DNA copy number was assessed by low-coverage DNA sequencing (n = 30) or array-comparative genomic hybridisation (n = 32). Adenomas were classified into CMS classes together with CRCs from the study cohort and from The Cancer Genome Atlas (n = 556), by use of the established CMS classifier. As a result, 54 of 62 (87%) adenomas were classified according to the CMS. The CMS3 ‘metabolic subtype’, which was least common among CRCs, was most prevalent among adenomas (n = 45; 73%). One of the two adenomas showing MSI was classified as CMS1 (2%), the ‘MSI immune’ subtype. Eight adenomas (13%) were classified as the ‘canonical’ CMS2. No adenomas were classified as the ‘mesenchymal’ CMS4, consistent with the fact that adenomas lack invasion-associated stroma. The distribution of the CMS classes among adenomas was confirmed in an independent series. CMS3 was enriched with adenomas at low risk of progressing to CRC, whereas relatively more high-risk adenomas were observed in CMS2. We conclude that adenomas can be stratified into the CMS classes. Considering that CMS1 and CMS2 expression signatures may mark adenomas at increased risk of progression, the distribution of the CMS classes among adenomas is consistent with the proportion of adenomas expected to progress to CRC

Quantificação de fatores de crescimento na pele de equinos tratada com plasma rico em plaquetas

O plasma rico em plaquetas (PRP) é um produto derivado da centrifugação do sangue total, sendo rico em fatores bioativos, como os de crescimento. Apesar da ampla utilização em processos cicatriciais, há controvérsia sobre a eficácia da terapia na cicatrização cutânea. O objetivo desse estudo foi quantificar e comparar a concentração dos fatores TGF-β1 e PDGF-BB no PRP, plasma sanguíneo e pele, durante diferentes fases do processo de cicatrização da pele tratada ou não com PRP. Foram utilizados sete equinos machos castrados, mestiços, hígidos, com idade entre 16 e 17 (16,14±0,63) anos. Três lesões em formato quadrangular (6,25cm²) foram produzidas cirurgicamente nas regiões glúteas direita e esquerda de todos os animais. Doze horas após indução das feridas, 0,5mL do PRP foi administrado em cada uma das quatro extremidades das feridas de uma das regiões glúteas (Grupo tratado = GT), escolhida aleatoriamente. A região contralateral foi utilizada como controle (GC). As feridas foram submetidas à limpeza diária com água Milli Q, e amostras foram obtidas mediante biópsias realizadas com Punch de 6mm. Foram obtidas seis biópsias de pele, sendo a primeira realizada logo após a produção da ferida (T0), e as demais com 1 (T1) 2 (T2) 7 (T3) e 14 (T4) dias após a indução da lesão. A sexta biópsia (T5) foi obtida após completo fechamento da pele, que ocorreu aproximadamente aos 37 dias (36,85±7,45, GC; 38,85±6,46, GT). Também foram obtidas amostras de sangue com EDTA em todos os tempos mencionados. A quantificação dos fatores de crescimento TGF-β1 e PDGF-BB na pele, PRP e plasma sanguíneo foi realizada pela técnica ELISA. Os dados foram analisados estatisticamente pelo teste t, correlação de Pearson e regressão, utilizando nível de significância de 5%. Não houve diferença entre os grupos, nos valores dos dois fatores de crescimento mensurados na pele, nos diferentes tempos. Também não houve correlação entre a quantidade dos fatores de crescimento presentes na pele e no plasma. Por outro lado, correlação positiva foi observada entre PRP e pele no grupo tratado, para os fatores de crescimento TGF-β1 (r=0,31) e PDGF-BB (r=0,38), bem como entre ambos os fatores de crescimento presentes no PRP (r=0,81). Considerando as concentrações dos fatores de crescimento no T0, os maiores valores cutâneos (p<0,05) do TGF-β1, em ambos os grupos, ocorreram nos tempos T3 e T5. Valores mais elevados (p<0,05) do PDGF-BB ocorreram no T4 (GT) e T5 (GC). No plasma não houve alteração nas concentrações desses fatores em relação ao T0, o que sugere que o PRP não acarreta efeito sistêmico, quando os procedimentos adotados na presente pesquisa são utilizados. A administração local de PRP no volume estudado, 12 h após indução cirúrgica de ferida cutânea na região glútea de equinos não ocasiona maiores concentrações dos fatores de crescimento TGF-β1 e PDGF-BB no plasma sanguíneo e pele, durante o processo de cicatrização

Volumetric breast density from full-field digital mammograms and its association with breast cancer risk factors: a comparison with a threshold method.

INTRODUCTION: Breast density, a strong breast cancer risk factor, is usually measured on the projected breast area from film screen mammograms. This is far from ideal, as breast thickness and technical characteristics are not taken into account. We investigated whether volumetric density measurements on full-field digital mammography (FFDM) are more strongly related to breast cancer risk factors than measurements with a computer-assisted threshold method. METHODS: Breast density was measured on FFDMs from 370 breast cancer screening participants, using a computer-assisted threshold method and a volumetric method. The distribution of breast cancer risk factors among quintiles of density was compared between both methods. We adjusted for age and body mass index (BMI) with linear regression analysis. RESULTS: High percent density was strongly related to younger age, lower BMI, nulliparity, late age at first delivery and pre/perimenopausal status, to the same extent with both methods (all P < 0.05). Similarly strong relationships were seen for the absolute dense area but to a lesser extent for absolute dense volume. A larger dense volume was only significantly associated with late age at menopause, use of menopausal hormone therapy, and, in contrast to the other methods, high BMI. CONCLUSION: Both methods related equally well to known breast cancer risk factors. IMPACT: Despite its alleged higher precision, the volumetric method was not more strongly related to breast cancer risk factors. This is in agreement with other studies. The definitive relationship with breast cancer risk still needs to be investigated

Het Audi Duo concept in de praktijk: milieuprestaties en de kansen en belemmeringen voor marktintroductie, bepaald in het Demonstratieproject Audi duo

Gezamenlijk met ECN is dit rapport samengesteld. Dit rapport is bijdrage 2. Om de milieuprestaties van de Audi Duo in kaart te brengen is in het onderzoek voor de volgende emissies gekozen: koolstofmonoxide (CO), koolwaterstoffen (HC), stikstofoxiden (NOx), zwaveldioxide (SO2), deeltjes (PM), koolstofdioxide (CO2). De opwekking van elektrische energie en de productie van diesel gaat ook gepaard met emissies. Deze emissies zijn ook in het onderzoek betrokken. Om deze emissies te kunnen bepalen moet tevens het dieselverbruik en het elektrisch energiegebruik van het voertuig worden onderzocht. In de komende paragrafen wordt de methodiek besproken die gehanteerd is om de technologie, het gebruik van het voertuig en het gedrag van de bestuurder in relatie tot de milieuprestatie te onderzoeken

Systematic review and meta-analysis concerning near-infrared imaging with fluorescent agents to identify the sentinel lymph node in oncology patients

Sentinel node procedures (SNP) are performed with the use of tracer-agents, mainly radio-colloid and/or blue dye. Fluorescent agents have emerged as a new tracer-agent to identify the SLN intra-operatively with near-infrared imaging. Our aim is to compare the detection rate of fluorescent agents to current "golden standards" (blue dye and/or radio-colloid) for the SNP by means of a systematic review and meta-analysis without any restrictions based on tumor type.A systematic search in PubMed, Embase and The Cochrane Library was performed. Articles that compared the detection rates of fluorescent agents with radio-colloid and/or blue dye were included. Meta-analyses were performed for breast, gynecological and dermatological cancer using a random effects model.In total 6195 articles were screened which resulted in a final inclusion of 55 articles. All studies used indocyanine green (ICG) as fluorescent agent. Meta-analyses comparing ICG with blue dye showed a significant and clinically relevant difference in detection rate in favor of ICG, for both breast, dermatological and gynecological cancer. Meta-analyses comparing ICG with radio-colloid did not show any significant differences, with the exception of ICG versus radio-colloid + blue dye for the bilateral SLN detection in gynecological cancer.Near-infrared fluorescence imaging using ICG provides a higher detection rate compared to blue dye for the SNP in a range of different tumor types. SLN detection rates of ICG are comparable to radiocolloid. Due to their complementary characteristics in terms of spatial resolution and transdermal sensitivity, we suggest to use a combination of both ICG and a radio-colloid. (C) 2020 The Authors. Published by Elsevier Ltd.Development and application of statistical models for medical scientific researc

Efficacies of bacterial and fungal isolates in biocontrol of Botrytis cinerea and Pseudomonas syringae pv. tomato and growth promotion in tomato do not correlate

There is a need to develop more biological control agents to fulfil the increasing demand for biological crop protection. Testing for consistent efficacy in disease control under the relevant range of environmental conditions is one of the most demanding steps during screening programs. Bioassays were conducted to target three major diseases of tomato, stem canker caused by Botrytis cinerea, leaf spot caused by B. cinerea, and bacterial spot caused by Pseudomonas syringae pv. tomato, and to assess possible growth promotion of tomato seedlings. Nine quantitative screening approaches were analyzed for a test panel of approximately 100 isolates of bacteria and fungi, all obtained from tomato, and several known antagonists as reference isolates. Even with such a limited number of isolates promising antagonists, partly not yet described as antagonists, could be selected for control of the targeted diseases when labor and resource demanding in planta bioassays had been applied. Also some promising isolates enhancing seedling development could be identified. Independent screening assays for the different traits were needed since no correlation between the different traits were found. Attempts to simplify screening assays to high-throughput systems failed since there were no positive correlations with in planta bioassays. In conclusion, the often suggested first screening rounds using in vitro tests for huge numbers of isolates followed by in planta testing of a selected group of candidates, e.g. those with high in vitro production of certain secondary metabolites or biosurfactants, may not exploit the entire potential of antagonists. Especially antagonists combining various modes of action may be excluded by in vitro screening with a bias on a specific mode of action. Therefore, independent in planta assays are proposed to screen against different pathogens and for growth promotion

Process Mining: Discovering Direct Successors in Process Logs

Workflow management technology requires the existence of explicit process models, i.e. a completely specified workflow design needs to be developed in order to enact a given workflow process. Such a workflow design is time consuming and often subjective and incomplete. We propose a learning method that uses the workflow log, which contains information about the process as it is actually being executed. In our method we will use a logistic regression model to discover the direct connections between events of a realistic not complete workflow log with noise. Experimental results are used to show the usefulness and limitations of the presented method

Intraperitineal hypercoagulation and hypofibrinolysis is present in childhood peritonitis

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