The tumor microenvironment and immune targeting therapy in pediatric renal tumors

alexandrossfakianakis shared this article with you from Inoreader The tumor microenvironment and immune targeting therapy in pediatric renal tumors via Pediatric Blood & Cancer Abstract This review highlights the role of several immunomodulating elements contributing to the tumor microenvironment of various pediatric renal tumors including Wilms tumor. The roles of innate and adaptive immune cells in renal tumors are summarized as well as immunomodulatory cytokines and other proteins. The expression and the predictive role of checkpoint modulators like PD-L1 and immunomodulating proteins like glypican-3, B7-H3, COX-2 are highlighted with a translational view toward potential therapeutic innovations. We further discuss the current state of preclinical models in advancing this field of study. Finally, examples of clinical trials of immunomodulating strategies such as monoclonal antibodies and chimeric antigen receptor T (CAR-T) cells for relapsed/refractory/progressive pediatric renal tumors are described. View on Web

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Management of biologics in pregnant, lactating patients with inflammatory bowel disease and the impact on neonatal vaccination: A systematic review of clinical practice guidelines and consensus statements

alexandrossfakianakis shared this article with you from Inoreader Management of biologics in pregnant, lactating patients with inflammatory bowel disease and the impact on neonatal vaccination: A systematic review of clinical practice guidelines and consensus statements via Journal of Clinical Pharmacy and Therapeutics Biologics can be given safely during pregnancy but require suspension at the right time to protect the foetus, The roles of vedolizumab and ustekinumab are vague. The use of most biologics during lactation is safe, but no guidelines recommend vedolizumab. A delay in infants' live vaccination schedule is needed if their mothers are treated with biologics. Abstract What Is Known and Objective The management of biological agents during pregnancy poses challenges as maternal and infant safety must be addressed. This study aims to compare the recommendations of existing guidelines on managing the use of biologics during pregnancy, lactation for patients with inflammatory bowel disease, and the influence on neonatal vaccination. Methods The PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database and China Biomedical Database were systematically searched from the inception date to 11 May 2022, to screen all relevant guidelines. Quality assessment was performed using the guideline methodology reporting tool AGREE II. Results and Discussion Fourteen guidelines and consensus statements with detailed recommendations were included. All guidance documents cover management comments during pregnancy, and most consider that biologics can be given safely during pregnancy but require suspension at the right time to protect the foetus. However, the roles of vedolizumab and ustekinumab are disputed. Five documents guide lactation and the use of most biologics during lactation is safe, but no guidelines recommend vedolizumab. Six papers provide recommendations for newborns' vaccination, suggesting a delay in infants' live vaccination schedule if their mothers are treated with biologics. What Is New and Conclusion Our study concluded that future guidelines could consider incorporating newer, more robust evidence to update recommendations. The development of future guidelines needs to consider the involvement of multidisciplinary experts, adequately report on the evidence retrieval process, and provide strategies for implementation. Besides, more research is needed to explore the use of biologics during pregnancy and lactation in patients with inflammatory bowel disease. View on Web

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Patient experiences of weight loss and eating after bariatric surgery: A Systematic Review and Qualitative Synthesis

alexandrossfakianakis shared this article with you from Inoreader Patient experiences of weight loss and eating after bariatric surgery: A Systematic Review and Qualitative Synthesis via Journal of Human Nutrition and Dietetics Abstract Background An estimated 26% of men and 29% of women in the UK are living with obesity according to recent statistics. Bariatric Surgery (BS) can induce significant weight loss and improve co-morbidity status. However previous studies highlight challenges in maintaining dietary changes and weight loss. This systematic review aimed to investigate patient experiences of weight loss and eating in the first two years following surgery, to provide clinical recommendations to support this group. Methods Ethical approval was granted by the University. A systematic search was conducted in four databases. Studies were selected according to the predefined eligibility criteria and methodological quality, assessed via the CASP tool. Data were extracted and analysed using a thematic synthesis method. Rigour was enhanced via use of a data extraction tool, a validated method for data synthesis, peer-review and transparent reporting. Results In total, 507 record s were screened; nine studies met the inclusion criteria. The thematic synthesis yielded four, interlinked analytical themes based on 154 patients' experiences: relationship with food, relationship with oneself, relationship with others and unfinished journey. Positive experiences were reported including development of healthy eating behaviours and significant weight loss, improving physical and psychosocial wellbeing. On the other hand, challenges in adjusting to life after surgery were also reported. Conclusions This study highlighted the need for personalised dietary advice, addressing the psychological aspects of eating. Support should be extended to the family. Ongoing psychological support must be incorporated in the post-surgery care pathway to help patients deal with the negative outcomes of surgery such as excess skin. This article is protected by copyright. All rights reserved. View on Web

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A comprehensive single cell data analysis of in lymphoblastoid cells reveals the role of Super‐enhancers in maintaining EBV latency

alexandrossfakianakis shared this article with you from Inoreader A comprehensive single cell data analysis of in lymphoblastoid cells reveals the role of Super‐enhancers in maintaining EBV latency via Journal of Medical Virology Abstract We probed the lifecycle of EBV on a cell-by-cell basis using single cell RNA sequencing (scRNA-seq) data from nine publicly available lymphoblastoid cell lines (LCL). While the majority of LCLs comprised cells containing EBV in the latent phase, two other clusters of cells were clearly evident and were distinguished by distinct expression of host and viral genes. Notably, both were high expressors of EBV LMP1/BNLF2 and BZLF1 compared to another cluster that expressed neither gene. The two novel clusters differed from each other in their expression of EBV lytic genes, including glycoprotein gene GP350. The first cluster, comprising GP350 – LMP1 hi cells, expressed high levels of HIF1A and was transcriptionally regulated by HIF1-α. Treatment of LCLs with Pevonedistat, a drug that enhances HIF1-α signaling, markedly induced this cluster. The second cluster, containing GP350 + LMP1 hi cells, expressed EBV lytic genes. Host genes that are controlled by super-enhancers (SEs), such as transcription factors MYC and IRF4, had the lowest expression in this cluster. Functionally, the expression of genes regulated by MYC and IRF4 in GP350 + LMP1 hi cells were lower compared to other cells. Indeed, induction of EBV lytic reactivation in EBV+ AKATA reduced the expression of these SE-regulated genes. Furthermore, CRISPR-mediated perturbation of the MYC or IRF4 SEs in LCLs induced the lytic EBV gene expression, suggesting that host SEs and/or SE target genes are required for maintenance of EBV latency. Collectively, our study revealed EBV associated heterogeneity among LCLs that may have functional consequence on host and viral biology. This article is protected by copyright. All rights reserved. View on Web

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Kutane Plattenepithelkarzinome im Kopf- und Halsbereich

alexandrossfakianakis shared this article with you from Inoreader Kutane Plattenepithelkarzinome im Kopf- und Halsbereich via Laryngo-Rhino-Otologie Laryngorhinootologie DOI: 10.1055/a-1953-7374 Hintergrund Das kutane Plattenepithelkarzinom (kPEK) als weltweit zweithäufigster Hauttumor ist überwiegend an Kopf und Gesicht lokalisiert. Aufgrund der steigenden Anzahl älterer Menschen und der dadurch zunehmenden Inzidenz gewinnt es in den letzten Jahren an Relevanz im HNO-Fachgebiet. Material und Methoden Diese Übersichtsarbeit basiert auf einer selektiven Literaturrecherche in PubMed, der deutschen und europäischen Leitlinie sowie klinikeigenen Erfahrungen. Ergebnisse Ätiologisch ist neben der chronischen UV-Exposition eine Störung des körpereigenen Abwehrsystems zunehmend bedeutend. Die vertikale Tumordicke ist mit dem höchsten Risiko einer Metastasierung und eines Lokalrezidivs assoziiert. Weitere bedeutende Risikofaktoren sind: horizontaler Tumordurchmesser, Entdifferenzierung, Desmoplasie, perineurales Wachstum und Lokalisation im Gesicht. Zumeist ist die Exzision mit histologischer Schnittrandkontrolle als Therapie ausreichend. Bei klinischem Verdacht auf lokoregionäre Metastasen sollen je nach Lokalisation des Primärtumors die drainierenden zervikalen Lymphknotenlevel ausgeräumt werden. kPEK der oberen Gesichtshaut und der Ohrmuschel metastasieren bevorzugt zuerst in die Glandula parotidea. Mit der Zulassung des PD-1-Antikörpers Cemiplimab in Europa steht erstmals ein Wirkstoff zur Behandlung fortgeschrittener, chirurgisch oder durch Strahlentherapie nicht therapierbarer kPEK zur Verfügung. Schlussfolgerungen Die grundsätzlich sehr niedrige Mortalität des kPEK erhöht sich erheblich, wenn Metastasen auftreten. Dementsprechend sollen sich bildgebende Verfahren, chirurgische Therapie und Nachsorgeintervalle an den Risikofaktoren orientieren. Hierdurch können Metastasen oder Lokalrezidive frühzeitig erkannt und die Prognose verbessert werden. [...] Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on Web

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