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

alexandrossfakianakis shared this article with you from Inoreader Imaging of pediatric neuroblastoma: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper via Pediatric Blood & Cancer ABSTRACT Neuroblastoma is the most common extracranial solid neoplasm in children. This manuscript provides consensus-based imaging recommendations for pediatric neuroblastoma patients 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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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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Bupivacaine inhibits the TLR4 ‐ and TLR2 ‐ Myd88/NF‐κB pathways in human leukocytes

alexandrossfakianakis shared this article with you from Inoreader Bupivacaine inhibits the TLR4 ‐ and TLR2 ‐ Myd88/NF‐κB pathways in human leukocytes via Fundamental & Clinical Pharmacology Abstract Background Local anesthetics have anti-inflammatory effects. Because most previous experiments were performed with supra-therapeutic concentrations, we measured the effects of clinically relevant concentrations of bupivacaine on the TLR4- and TLR2-MyD88-NF-κB pathways. Methods We measured TNF-α and PGE2 release, p38 MAP-kinase phosphorylation and translocation of NF-κB in human peripheral blood mononuclear cells (hPBMC) and human monocytes challenged with LPS (lipopolysaccharide) or Pam3CSK4 (tripalmitoylated lipopeptide Pam3CysSerLys4) in the presence or absence of bupivacaine. Similarly, we measured the effect of bupivacaine on HEK293 cells expressing the hTLR4 and the hTLR2 genes and challenged with LPS or Pam3CSK4. Finally, molecular docking simulations of R(+)- and S(-)-bupivacaine binding to the TLR4-MD-2 complex and to the TLR2/TLR1 heterodimer were performed. Results In PBMCs, bupivacaine from 0.1 to 100 μM inhibited LPS-induced TNF-α and PGE2 secretion, phosphorylation of p38 and nuclear translocation of NF-κB in monocytes. Bupivacaine similarly inhibited the effects of Pam3CSK4 on TNF-α secretion. Bupivacaine inhibited the effect of LPS on HEK293 cells expressing the human TLR4 receptor and the effect of Pam3CSK4 on HEK293 cells expressing the human TLR2 receptor. Molecular docking showed that bupivacaine binds to the MD-2 co-receptor of TLR4 and to the TLR2 receptor. Conclusions Contrary to numerous experiments performed with supratherapeutic doses, our results were obtained with concentrations of bupivacaine as low as 0.1 μM. We conclude that bupivacaine modulates the inflammatory reactions such as those observed after surgery or trauma, at least partly by inhibiting the TLR4- and TLR2-NF-κB pathways. View on Web

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Immunomodulatory effect of IL‐1RA in LPS activated macrophage/dental pulp stem cells co‐culture

alexandrossfakianakis shared this article with you from Inoreader Immunomodulatory effect of IL‐1RA in LPS activated macrophage/dental pulp stem cells co‐culture via International Endodontic Journal Abstract Aims: Lipopolysaccharides (LPS) activated human dental pulp stem cells (hDPSCs) and macrophage co-cultures showed downregulated TNF-α secretion that is modulated by hDPSCs through IDO axis, whereas the secretory levels of IL-1β remained unchanged. Therefore, sustained production of IL-1β could contribute to progressive dental pulp inflammation. However, the role of IL-1 receptor antagonists (IL-1RA) in downregulating the secretion of IL-1β and TNF-α in LPS activated M0/M1/M2 macrophage and hDPSCs co-culture has not been studied yet. Therefore, the aim of the present study is to determine the immunomodulatory role of blocking IL-1 receptors in DPSCs macrophage co-culture activated with LPS. Methodology: Human monocytic cell line THP-1 was polarised to M0, M1, and M2 macrophages and co-cultured with hDPSCs. The viability of the co-cultured cells was assessed by apoptosis assay. Co-cultures were activated with LPS followed by the assessment of gene expression and protein levels of IL-1β and TNF-α with and without IL-1RA blocking via qRT-PCR and cytokine flex assay by flow cytometry. Data from three separate experiments was analysed using One-way ANOVA followed by Tukey's Post-hoc test and a p value of <0.05 was considered statistically significant. Results: THP-1 derived M0, M1, and M2 macrophages co-cultured with hDPSCs showed spindle and round-shaped cells, with > 90% viability when assessed by apoptosis assay. Inflammatory TNF-α and IL-1β profile in stimulated co-cultures showed upregulated IL-1β whereas TNF-α was downregulated (p< 0.05). Anti-inflammatory gene expression levels of IL-10, TGF-β were downregulated (p< 0.05). Blocking with IL-1RA resulted in remarkable decrease of IL-1β at the gene expression and protein production levels while TNF-α levels remained low (p< 0.05). Levels of anti-inflammatory cytokine IL-10 showed no significant difference. Conclusion: Blocking the IL-1 receptor in hDPSCs and macrophage (M0, M1, M2) co-cultures activated with LPS resulted in down regulation of inflammatory cytokines IL-1β and TNF-α. These findings highlight the immunomodulatory effect of IL-1RA in inflammatory conditions of dental pulp infections. View on Web

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Estimation of the time-varying incremental effect of low dose aspirin on incidence of pregnancy

alexandrossfakianakis shared this article with you from Inoreader Estimation of the time-varying incremental effect of low dose aspirin on incidence of pregnancy via Epidemiology - Published Ahead-of-Print Background. In many research settings, the intervention implied by the average causal effect of a time-varying exposure is impractical or unrealistic, and we might instead prefer a more realistic target estimand. Instead of requiring all individuals to be always exposed vs. unexposed, incremental effects quantify the impact of merely shifting each individual's probability of being exposed. Methods. We demonstrate estimation of incremental effects in the time-varying setting, using data from the Effects of Aspirin in Gestation and Reproduction trial, which assessed the effect of preconception low-dose aspirin on pregnancy outcomes. Compliance to aspirin or placebo was summarized weekly and was affected by time-varying confounders such as bleeding or nausea. We sought to estimate what the incidence of pregnancy by 26 weeks post-randomization would have been if we shifted each participant's probability of taking aspirin or placebo in each week by odds ratios (OR) between 0.30 and 3.00. Results. Under no intervention (OR=1), the incidence of pregnancy was 77% (95% CI: 74%, 80%). Decreasing women's probability of complying with aspirin had little estimated effect on pregnancy incidence. When we increased women's probability of taking aspirin, estimated incidence of pregnancy increased, from 83% (95% CI: 79%, 87%) for OR=2 to 89% (95% CI: 84%, 93%) for OR=3. We observed similar results when we shifted women's probability of complying with placebo. Conclusions. These results estimated that realistic interventions to increase women's probability of taking aspirin would have yielded little to no impact on the incidence of pregnancy, relative to similar interventions on placebo. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. View on Web

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Magnetic Resonance Imaging Directed Surgical Decision Making for Lateral Pelvic Lymph Node Dissection in Rectal Cancer After Total Neoadjuvant Therapy (TNT)

alexandrossfakianakis shared this article with you from Inoreader Magnetic Resonance Imaging Directed Surgical Decision Making for Lateral Pelvic Lymph Node Dissection in Rectal Cancer After Total Neoadjuvant Therapy (TNT) via Annals of Surgery - Most Popular Articles Objective: Lateral pelvic lymph node (LPLN) metastases are an important cause of preventable local failure in rectal cancer. The aim of this study was to evaluate clinical and oncological outcomes following magnetic resonance imaging (MRI)-directed surgical selection for lateral pelvic lymph node dissection (LPLND) after total neoadjuvant therapy (TNT). Methods: A retrospective consecutive cohort analysis was performed of rectal cancer patients with enlarged LPLN on pretreatment MRI. Patients were categorized as LPLND or non-LPLND. The main outcomes were lateral local recurrence rate, perioperative and oncological outcomes and factors associated with decision making for LPLND. Results: A total of 158 patients with enlarged pretreatment LPLN and treated with TNT were identified. Median follow-up was 20 months (interquartile range 10–32). After multidisciplinary review, 88 patients (56.0%) underwent LPLND. Mean age was 53 (SD±12) years, and 54 (34.2%) were female. Total operative time (509 vs 429 minutes; P=0.003) was greater in the LPLND group, but median blood loss (P=0.70) or rates of major morbidity (19.3% vs 17.0%) did not differ. LPLNs were pathologically positive in 34.1%. The 3-year lateral local recurrence rates (3.4% vs 4.6%; P=0.85) did not differ between groups. Patients with LPLNs demonstrating pretreatment heterogeneity and irregular margin (odds ratio, 3.82; 95% confidence interval: 1.65–8.82) or with short-axis ≥5 mm post-TNT (odds ratio 2.69; 95% confidence interval: 1.19–6.08) were more likely to undergo LPLND. Conclusions: For rectal cancer patients with evidence of LPLN metastasis, the appropriate selection of patients for LPLND can be facilitated by a multidisciplinary MRI-directed approach with no significant difference in perioperative or oncologic outcomes. View on Web

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Polyethylenglycol – Freund oder Feind?

alexandrossfakianakis shared this article with you from Inoreader Polyethylenglycol – Freund oder Feind? via Laryngo-Rhino-Otologie Laryngorhinootologie 2022; 101: 784-786 DOI: 10.1055/a-1861-7047 Anaphylaktische Reaktionen nach Impfungen sind selten. Zwei Fälle von Reaktionen nach der Pfizer-BioNTech-Covid-19-Vakzine, BNT162b2, wurden aus dem UK berichtet, weitere 19 aus den USA. Als möglicher Auslöser wurde Polyethylenglycol (PEG) angeschuldigt. Pegylierung ist ein üblicher Vorgang in der Impfstoffherstellung, um die Substanzen vor schnellem immunologischem Abbau zu schützen. PEG ist ein Polyether (Synonyme z. B. Laureth-9, Polidocanol, Thesit, Macrogol) und findet sich in Kosmetika, Körperpflegeprodukten, Nahrungsmitteln, Liposomen und Nanopartikeln als Drug-Delivery-Systeme für Medikamente und als osmotisches Laxans vor Gastro-/Koloskopien. IgM-Antikörper auf PEG werden bei 70% der Bevölkerung nachgewiesen. Bei 2 Fällen von Soforttyp-Reaktionen auf PEG fanden sich IgE-Antiköper, bei anderen Medikamentengaben mit PEG geht man von pseudoallergischen Reaktionen über die Komplement-Aktivierungs-related Pseudoallergie (CARPA) aus. In Relation zum weit verbreiteten Einsatz von PEG sind die Impfreaktionen sehr selten und aktuell kein Grund, Allergiker oder Menschen mit Anaphylaxien bei entsprechenden Vorsichtsmaßnahmen auf bekannte Auslöser auszuschließen. Aufgrund der Meldepflicht (Gesundheitsamt und Arzneimittelkommission der deutschen Ärzteschaft) ist bald mit weiteren Erkenntnissen zu rechnen. [...] 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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