Booster vaccination against SARS-CoV-2 induces potent immune responses in people with HIV

alexandrossfakianakis shared this article with you from Inoreader Booster vaccination against SARS-CoV-2 induces potent immune responses in people with HIV via Clinical Infectious Diseases Advance Access Abstract Background People with HIV on antiretroviral therapy with good CD4 T cell counts make effective immune responses following vaccination against SARS-CoV-2. There are few data on longer term responses and the impact of a booster dose. Methods Adults with HIV were enrolled into a single arm open label study. Two doses of ChAdOx1 nCoV-19 were followed twelve months later by a third heterologous vaccine dose. Participants had undetectable viraemia on ART and CD4 counts >350 cells/µl. Immune responses to the ancestral strain and variants of concern were measured by anti-spike IgG ELISA, MesoScale Discovery (MSD) anti-spike platform, ACE-2 inhibition, Activation Induced Marker (AIM) assay and T cell proliferation. Findings 54 participants received two doses of ChAdOx1 nCoV-19. 43 received a third dose (42 with BNT162b2; 1 with mRNA-1273) one year after the first dose. After the third dose, total anti-SARS-CoV-2 spike IgG titres (MSD), ACE-2 inhibition and IgG ELISA results were significantly higher compared to Day 182 titres (P < 0.0001 for all three). SARS-CoV-2 specific CD4+ T cell responses measured by AIM against SARS-CoV-2 S1 and S2 peptide pools were significantly increased after a third vaccine compared to 6 months after a first dose, with significant increases in proliferative CD4 + and CD8+ T cell responses to SARS-CoV-2 S1 and S2 after boosting. Responses to Alpha, Beta, Gamma, and Delta variants were boosted, although to a lesser extent for Omicron. Conclusions In PWH receiving a third vaccine dose, there were significant increases in B and T cell immunity, including to known VOCs. View on Web

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Role of sentinel lymph node biopsy for oral squamous cell carcinoma: Current evidence and future challenges

alexandrossfakianakis shared this article with you from Inoreader Role of sentinel lymph node biopsy for oral squamous cell carcinoma: Current evidence and future challenges via Head & Neck Abstract Sentinel lymph node biopsy (SLNB) has been used across oncological specialties for prognostication, staging, and identification of occult nodal metastasis. Recent studies demonstrated the potential clinical utility of SLNB in oral cavity squamous cell carcinoma (OCSCC). Elective neck dissection is the current standard of care in early management of OCSCC with depth of invasion greater than 2–4 mm; however, majority of patients ultimately do not have nodal disease on final pathology. SLNB is an alternative procedure widely adopted in early cancer management in many oncological subspecialities. Several considerations such as depth of invasion, nodal mapping, histopathology methods, operator variability, postoperative complications, and advancement in preoperative and intraoperative imaging technology can guide the appropriate application to SLNB in OCSCC. The aim of this review is to discuss the current evidence for SLNB in the treatment of early stage OCSCC, imaging technologie s that support SLNB procedures, and studies that are currently underway. View on Web

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RNA‐sequencing analysis reveals potential molecular mechanism of RAD54B in the proliferation of inflamed human dental pulp cells

alexandrossfakianakis shared this article with you from Inoreader RNA‐sequencing analysis reveals potential molecular mechanism of RAD54B in the proliferation of inflamed human dental pulp cells via International Endodontic Journal Abstract Aim To investigate the role of RAD54B in the proliferation of inflamed human dental pulp cells (hDPCs) induced by lipopolysaccharide (LPS). Methodology Normal, carious, and pulpitic human dental pulp tissues were collected. Total RNA was subjected to RNA-sequencing (seq) and gene expression profiles were studied by Gene Ontology (GO) and KEGG pathway analysis. Differentially expressed genes (DEGs) in homologous recombination repair (HRR) were validated with qRT-PCR. The expression of RAD54B and TNF-α in human dental pulp tissues was detected using immunohistochemistry. HDPCs were cultured and RAD54B level in hDPCs was detected after LPS stimulation using western blot. CCK-8 was used to investigate the proliferation of hDPCs transfected with negative control (Nc) small interfering RNA (siRNA), RAD54B siRNA, P53 siRNA or both siRNAs with or without LPS stimulation. Flow cytometry was used to detect the cell cycle distribution, and western blot and immunofluorescence were used to analyze the expression of RAD54B, P53 and P21 under the above treatments. One-way and two-way ANOVA followed by LSD posttest were used for statistical ana lysis. Results RNA-seq results identified DEGs among the three groups. KEGG pathway analysis revealed enrichment of DEGs in the replication and repair pathway. HRR and non-homologous end joining (NHEJ) components were further verified and qRT-PCR results were basically consistent with the sequencing data. RAD54B, an HRR accessory factor highly expressed in carious and pulpitic tissues as compared to that in the normal pulps, was chosen as our gene of interest. High RAD54B expression was confirmed in inflamed human dental pulp tissues and LPS-stimulated hDPCs. Upon RAD54B knockdown, P53 and P21 expressions in hDPCs were upregulated whereas the proliferation was significantly downregulated, accompanied by increased G2/M phase arrest. After inhibiting P53 expression in RAD54B-knockdown hDPCs, P21 expression and cell proliferation were reversed. Conclusions Gene expression profiles of normal, carious and pulpitic human dental pulp tissues were revealed. HRR components was elucidated to function in dental pulp inflammation. Among the DEGs in HRR, RAD54B regulated the proliferation of inflamed hDPCs via P53/P21 signalling. This research deepens understanding of dental pulp inflammation and provides a new insight to clarify the underlying mechanisms. View on Web

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Irinotecan dose schedule for the treatment of Ewing sarcoma

alexandrossfakianakis shared this article with you from Inoreader Irinotecan dose schedule for the treatment of Ewing sarcoma via Pediatric Blood & Cancer Abstract Irinotecan and temozolomide achieve objective responses in patients with Ewing sarcoma that recurs after initial therapy. Optimal dose schedules have not been defined. We reviewed published series of patients treated with irinotecan and temozolomide for Ewing sarcoma that recurred after initial therapy. We compared objective response rates for patients who received 5-day irinotecan treatment schedules to response rates for patients who achieved 10-day irinotecan treatment schedules. Among 89 patients treated with a 10-day irinotecan schedule, there were 47 objective responses (53%). Among 180 patients treated with a 5-day irinotecan schedule, there were 52 responses (29%). In the treatment of recurrent Ewing sarcoma, investigators should consider the use of a 10-day schedule for administration of irinotecan. View on Web

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Anaplastic lymphoma kinase positive histiocytosis presenting as hemocytopenia in an infant

alexandrossfakianakis shared this article with you from Inoreader Anaplastic lymphoma kinase positive histiocytosis presenting as hemocytopenia in an infant via Pediatric Blood & Cancer View on Web

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Imaging of pediatric ovarian tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

alexandrossfakianakis shared this article with you from Inoreader Imaging of pediatric ovarian tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper via Pediatric Blood & Cancer Abstract Ovarian tumors in children are uncommon. Like those arising in the adult population, they may be broadly divided into germ cell, sex cord, and surface epithelium subtypes; however, germ cell tumors comprise the majority of lesions in children, whereas tumors of surface epithelial origin predominate in adults. Diagnostic workup, including the use of imaging, requires an approach that often differs from that required in an adult. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary ovarian malignancy at diagnosis and during follow-up. View on Web

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Relationship between the timing of chemotherapy and surgical complications following surgical biopsy in children with malignant solid tumors

alexandrossfakianakis shared this article with you from Inoreader Relationship between the timing of chemotherapy and surgical complications following surgical biopsy in children with malignant solid tumors via Pediatric Blood & Cancer Abstract Background Biopsies for diagnosis before chemotherapy is common in children with malignant solid tumors. Wound healing is delayed by chemotherapy; however, the ideal interval between biopsy and chemotherapy remains unknown. We aimed to summarize the relationship between chemotherapy timing and postoperative surgical complications. Procedure We retrospectively reviewed patients with malignant solid tumors who underwent chemotherapy after surgical biopsy at our institution between January 2014 and August 2020. The primary outcomes were postoperative surgical complications (within 30 days) and the timing of chemotherapy. Results Forty-three patients were analyzed. The types of tumors were neuroblastoma (n = 20), hepatoblastoma (n = 10), Ewing sarcoma (n = 5), germ cell tumor (n = 3), angiosarcoma (n = 1), clear cell sarcoma (n = 1), ganglioneuroblastoma (n = 1), rhabdoid tumor (n = 1), and rhabdomyosarcoma (n = 1). The operative procedures were thoracoscopy (n = 5), laparotomy (n = 17), laparoscopy (n = 14), and superficial (n = 7). The median time [range] to chemotherapy after biopsy was 4 [0–21] days. No surgical complications occurred before chemotherapy, and two (4.7%) patients experienced complications after chemotherapy. These included postoperative hemorrhage (grade 3) and surgical site infection (grade 1). Chemotherapy was initiated 1 and 6 days after biopsy, respectively, in these cases. Complications occurred 10 and 23 days after biopsy, respectively. Conclusion The rate of postoperative surgical complications related to biopsy seems acceptable, even when chemotherapy was initiated in the early postoperative period. Early initiation of chemotherapy after biopsy may be a suitable option, particularly in children with bulky or symptomatic malignant solid tumors. View on Web

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Imaging of pediatric adrenal tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

alexandrossfakianakis shared this article with you from Inoreader Imaging of pediatric adrenal tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper via Pediatric Blood & Cancer Abstract Adrenal tumors other than neuroblastoma are uncommon in children. The most frequently encountered are adrenocortical carcinoma and pheochromocytoma. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary adrenal malignancy other than neuroblastoma at diagnosis and during follow-up. View on Web

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Surgical margins of the oral cavity: is 5 mm really necessary?

alexandrossfakianakis shared this article with you from Inoreader Surgical margins of the oral cavity: is 5 mm really necessary? via Most Recent Articles: Journal of Otolaryngology - Head & Neck Surgery Squamous cell carcinoma is the most common malignancy of the oral cavity. Primary treatment involves surgical resection of the tumour with a surrounding margin. Historically, the most commonly accepted margin ... View on Web

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Characterizing the biology of primary brain tumors and their microenvironment via single-cell profiling methods

alexandrossfakianakis shared this article with you from Inoreader Characterizing the biology of primary brain tumors and their microenvironment via single-cell profiling methods via Neuro-Oncology Advance Access Abstract Genomic and transcriptional heterogeneity is prevalent among the most common and aggressive primary brain tumors in children and adults. Over the past 20 years, advances in bioengineering, biochemistry and bioinformatics have enabled the development of an array of techniques to study tumor biology at single-cell resolution. The application of these techniques to study primary brain tumors has helped advance our understanding of their intra-tumoral heterogeneity and uncover new insights regarding their co-option of developmental programs and signaling from their microenvironment to promote tumor proliferation and invasion. These insights are currently being harnessed to develop new therapeutic approaches. Here we provide an overview of current single-cell techniques and discuss relevant biology and therapeutic insights uncovered by their application to primary brain tumors in children and adults. View on Web

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Oral biofilm dysbiosis during experimental periodontitis

alexandrossfakianakis shared this article with you from Inoreader Oral biofilm dysbiosis during experimental periodontitis via Molecular Oral Microbiology Abstract Objectives We have previously characterized the main osteoimmunological events that occur during ligature periodontitis. This study aims to determine the polymicrobial community shifts that occur during disease development. Methods Periodontitis was induced in C57BL/6 mice using the ligature-induced periodontitis model. Healthy oral mucosa swabs and ligatures were collected every 3-days from 0 to 18 days post-ligature placement. Biofilm samples were evaluated by 16SrRNA gene sequencing (Illumina MiSeq) and QIIME. Timecourse changes were determined by relative abundance, diversity, and rank analyses (PERMANOVA, Bonferroni-adjusted). Results Microbial differences between health and periodontal inflammation were observed at all phylogenic levels. An evident microbial community shift occurred in 25 genera during the advancement of "gingivitis" (3-6d) to periodontitis (9-18d). From day 0–18, dramatic changes were identified Streptococcus levels, with an overall decrease (54.04-0.02%) as well an overall increase of Enterococcus and Lactobacillus (23.7-73.1% and 10.1%-70.2%, respectively). Alpha-diversity decreased to its lowest at 3d, followed by an increase in diversity as disease advancement. Beta-diversity increased after ligature placement, indicating that bone loss develops in response to a greater microbial variability (p = 0.001). Levels of facultative and strict anaerobic bacteria augmented over the course of disease progression, with a total of 8 species significantly different during the 18-day period. Conclusion The data supports that murine gingival inflammation and alveolar bone loss develop in response to microbiome shifts. Bacterial diversity increased during progression to bone loss. These findings further support the utilization of the periodontitis ligature model for microbial shift analysis under different experimental conditions. This article is protected by copyright. All rights reserved View on Web

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