Predictors of COVID-19 hospitalization after sotrovimab in hematologic malignancy patients during the BA.1 Omicron surge

alexandrossfakianakis shared this article with you from Inoreader Predictors of COVID-19 hospitalization after sotrovimab in hematologic malignancy patients during the BA.1 Omicron surge via Clinical Infectious Diseases Advance Access ABSTRACT Background Sotrovimab is an anti-spike neutralization monoclonal antibody (mAB) developed to reduce the risk of Coronavirus Disease 2019 (COVID-19) progression and advancement to hospitalization in high-risk patients. Currently, there is limited research describing the association of sotrovimab treatment in patients with hematologic malignancies (HM) and the predictive factors of hospitalization. Methods We performed an observational study of 156 consec utive cancer patients who received sotrovimab at Memorial Sloan Kettering Cancer Center in New York City during the BA.1 Omicron surge. We evaluated the demographic, clinical, and laboratory characteristics of the patients who had subsequent COVID-19-related hospitalization(s) compared to those who did not. Results Among the 156 study patients, seventeen (17, 11%) were hospitalized of which four were readmitted for COVID-19-related complications; three deaths were attributed to COVID-19. Results from multivariable logistic regression show significant factors associated with hospitalization include patients on anti-CD20 therapy (adjusted OR = 5.59, 95% CI (1.73 - 18.12), p = 0.004) and with relapse/refractory disease (adjusted OR = 5.69, 95% CI (1.69 - 19.16), p = 0.005). Additionally, whole-genome sequencing of SARS-CoV-2 detected high occurrences of mutations in the spike gene associated with treatment-related resistance longitudinal samples from 11 patients treate d with sotrovimab. Conclusions While sotrovimab is effective at reducing COVID-19 hospitalization and disease severity in HM patients when administered early, patients who received anti-CD20 antibodies showed substantial morbidity. Due to the high potential for resistance mutation to sotrovimab and increased morbidity in patients on anti-CD20 therapy, combination treatment should be explored to determine whether it provides added benefits compared to monotherapy. 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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Leigh syndrome is the main clinical characteristic of PTCD3 deficiency

alexandrossfakianakis shared this article with you from Inoreader Leigh syndrome is the main clinical characteristic of PTCD3 deficiency via Brain Pathology In this manuscript the authors describe three patients from two unrelated families carrying mutations in PTCD3 and provide definitive evidence that PTCD3 deficiency is associated to Leigh syndrome. Functional complementation studies performed in both, immortalized patients' fibroblasts and cell models demonstrated the pathogenicity of the identified variants and their impact on the mitochondrial function. Abstract Mitochondrial translation defects are a continuously growing group of disorders showing a large variety of clinical symptoms including a wide range of neurological abnormalities. To date, mutations in PTCD3, encoding a component of the mitochondrial ribosome, have only been reported in a single individual with clinical evidence of Leigh syndrome. Here, we describe three additional PTCD3 individuals from two unrelated families, broadening the genetic and phenotypic spectrum of this disorder, and provide definitive evidence that PTCD3 deficiency is associated with Leigh syndrome. The patients presented in the first months of life with psychomotor delay, respiratory insufficiency and feeding difficulties. The neurologic phenotype included dystonia, optic atrophy, nystagmus and tonic–clonic seizures. Brain MRI showed optic nerve atrophy and thalamic changes, consistent with Leigh syndrome. WES and RNA-seq identified compound heterozygous variants in PTCD3 in both famil ies: c.[1453-1G>C];[1918C>G] and c.[710del];[902C>T]. The functional consequences of the identified variants were determined by a comprehensive characterization of the mitochondrial function. PTCD3 protein levels were significantly reduced in patient fibroblasts and, consistent with a mitochondrial translation defect, a severe reduction in the steady state levels of complexes I and IV subunits was detected. Accordingly, the activity of these complexes was also low, and high-resolution respirometry showed a significant decrease in the mitochondrial respiratory capacity. Functional complementation studies demonstrated the pathogenic effect of the identified variants since the expression of wild-type PTCD3 in immortalized fibroblasts restored the steady-state levels of complexes I and IV subunits as well as the mitochondrial respiratory capacity. Additionally, minigene assays demonstrated that three of the identified variants were pathogenic by altering PTCD3 mRN A processing. The fourth variant was a frameshift leading to a truncated protein. In summary, we provide evidence of PTCD3 involvement in human disease confirming that PTCD3 deficiency is definitively associated with Leigh syndrome. 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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