Longitudinal Immune Response to Three Doses of mRNA Vaccine Against COVID-19 in Pediatric Patients Receiving Chemotherapy for Cancer

alexandrossfakianakis shared this article with you from Inoreader Longitudinal Immune Response to Three Doses of mRNA Vaccine Against COVID-19 in Pediatric Patients Receiving Chemotherapy for Cancer via Clinical Infectious Diseases Advance Access Abstract Our study in 21 pediatric cancer patients demonstrates that three doses of SARS-CoV-2 mRNA vaccine (BioNTech/Pfizer) elicited both humoral and cellular immunity in most patients during chemotherapy. Immunity was stronger in children with solid tumors and during maintenance therapy compared to those with hematological malignancies or during intensive chemotherapy. View on Web

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No Reduction in the 226-Hz Probe Tone Acoustic Reflex Amplitude Following Severe Inner Hair Cell Loss in Chinchillas

alexandrossfakianakis shared this article with you from Inoreader No Reduction in the 226-Hz Probe Tone Acoustic Reflex Amplitude Following Severe Inner Hair Cell Loss in Chinchillas via JARO - Journal of the Association for Research in Otolaryngology via MedWorm.com AbstractThe relationship between the middle ear acoustic reflex (AR) and inner hair cell (IHC) loss is currently unknown. Given that IHC are believed to convey nearly all acoustic information to the central auditory nervous system, it has been assumed that loss of IHC would significantly impact the AR. To evaluate this relationship, we assessed the presence and amplitude of the AR in chinchillas before and after treatment with carboplatin, an anticancer drug that reliably and selectively destroys IHC in this species. Baseline measures of hearing sensitivity, including auditory brainstem response (ABR) thresholds and distortion product otoacoustic emissions (DPOAE), were assessed and then re-evaluated following carboplatin treatment. Post-carboplatin ABR thresholds and DPOAE were found to b... View on Web

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Menopausal hormone therapy and subclinical cardiovascular disease in women with and without HIV

alexandrossfakianakis shared this article with you from Inoreader Menopausal hormone therapy and subclinical cardiovascular disease in women with and without HIV via Clinical Infectious Diseases Advance Access Abstract Background Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with HIV who have heightened immune activation and cardiovascular risks. Methods Among 609 post-menopausal women (1,234 person-visits) in the Women's Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis – carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004-2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors. Results Women (mean age = 51, 80% HIV+) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio = 0.57; 95% CI = [0.40, 0.80]; p < 0.01), 2.51 µm less progression of CIMT per year (95% CI = [-4.60, -0.41]; p = 0.02), and marginally lower incidence of plaque over ∼7 years (risk ratio = 0.38; 95% CI = [0.14, 1.03]; p = 0.06), compared with never users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment. Conclusions HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low. View on Web

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Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe COVID-19: The PANCOVID Randomized Clinical Trial

alexandrossfakianakis shared this article with you from Inoreader Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe COVID-19: The PANCOVID Randomized Clinical Trial via Clinical Infectious Diseases Advance Access Abstract Background This study was designed to evaluate if patients with high risk for severe COVID-19 would benefit from treatment with TDF/FTC followed by baricitinib in case of hypoxemia and systemic inflammation. Methods PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥ 2 comorbidities or older than 60 years conducted between 10 October 2020 and 23 September 2021. In the first randomization patients received TDF/FTC or not TDF/FTC. In the second randomization patients with room-air O2 saturation <95% and at least one increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in th e number of cases and a mortality rate substantially lower than expected EudraCT registration number: 2020-001156-18. Results Of the 355 included participants 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% CI 0.52-5.91; p= 0.379); it was 0.42 (95% CI 0.11-1.59; p= 0.201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI 0.66-1.40; p = 0.774); it was 0.90 (95%CI 0.61-1.33; p = 0.687) for those treated with baricitinib. Conclusions Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials. View on Web

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Cytocompatibility and bioactive potential of AH Plus Bioceramic Sealer: an in vitro study

alexandrossfakianakis shared this article with you from Inoreader Cytocompatibility and bioactive potential of AH Plus Bioceramic Sealer: an in vitro study via International Endodontic Journal Abstract Abstract Aim To assess the cytocompatibility and bioactive potential of the new calcium silicate cement-based sealer AH Plus Bioceramic Sealer (AHPbcs) on human periodontal ligament stem cells (hPDLSCs) compared to the epoxy resin-based sealer AH Plus (AHP) and the calcium silicate cement-based sealer Endosequence BC Sealer (ESbcs). Methodology Standardized sample discs and 1:1, 1:2, and 1:4 eluates of the tested materials were prepared. The following assays were performed: surface element distribution via SEM-EDX, cell attachment and morphology via SEM, cell viability via a MTT assay, cell migration/proliferation via a wound-healing assay, osteo/cemento/odontogenic marker expression via RT-qPCR, and cell mineralized nodule formation via Alizarin Red S staining. HPDLSCs were isolated from extracted third molars. Comparisons were made with hPDLSCs cultured in unconditioned (negative control) or osteogenic (positive control) culture media. Statistical significance was established at p<0.05. Results A higher peak of Ca2+ was detected from ESbcs compared with AHPbcs and AHP in SEM-EDX. Both AHPbcs and ESbcs showed significantly positive results in the cytocompatibility assays (cell viability, migration/proliferation, attachment, and morphology) compared with a negative control group, while AHP showed significant negative results. Both AHPbcs and ESbcs exhibited an upregulation of at least one osteo/odonto/cementogenic marker compared to the negative and positive control groups. Both ESbcs and AHPbcs showed a significantly higher calcified nodule formation than the negative and positive control groups, indicative of their biomineralization potential, and were also significantly higher than AHP group. Conclusion AH Plus Bioceramic Sealer exhibited a significantly higher cytocompatibility and bioactive potential than AH Plus, and a similar cytocompatibility to that of Endosequence BC Sealer. Endosequence BC Sealer exhibited a significantly higher mineralization potential than the other tested sealers. The results from this in vitro study act as supporting evidence for the use of AH Plus bioceramic sealer in root canal treatment. View on Web

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Newborn body composition and child cardiovascular risk markers: a prospective multi-ethnic Asian cohort study

alexandrossfakianakis shared this article with you from Inoreader Newborn body composition and child cardiovascular risk markers: a prospective multi-ethnic Asian cohort study via International Journal of Epidemiology - Advance Access Abstract Background Early epidemiological studies have associated low birthweight with increased cardiovascular risk. We aimed to examine whether the fat and fat-free components of birthweight have differing relationships with childhood cardiovascular risk markers. Methods In the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort, air displacement plethysmography was conducted within 24 h after delivery in 290 naturally conceived singletons. We investigated associations of newborn cohort-specific standardized z-score of fat mass, fat-free mass, body fat percentage and birthweight on child (at 6 years of age) carotid intima-media thickness, pulse wave velocity, blood pressure, prehypertension/hypertension (>110/70 mmHg) and standardized systolic and diastolic blood pressure (SBP and DBP) trajectories (at 3–6 years of age), taking account of maternal education, height, tobacco exposure, parity, ethnicity, child� �s sex, gestational age, age at follow-up, and other maternal factors. Results Clear inverse associations were seen for blood pressure with z-score of fat mass [SBP, β (95% CI): −1.31 mmHg (−2.57, −0.06); DBP: −0.79 mmHg (−1.74, 0.15)] and body fat percentage [SBP: −1.46 mmHg (−2.73, −0.19); DBP: −0.80 mmHg (−1.75, 0.16)], but not with fat-free mass [SBP: 0.27 mmHg (−1.29, 1.83)]; DBP: −0.14 mmHg (−1.30, 1.03)]. Being in the lowest tertile of fat mass or body fat percentage was associated with higher blood pressure trajectories and prehypertension/hypertension risk [OR (95% CI), fat mass: 4.23 (1.41, 12.68); body fat percentage: 3.22 (1.09, 9.53)] without concomitantly higher overweight/obesity risk. Conclusions At birth, low adiposity was associated with increased childhood blood pressure. Low newborn adiposity might serve as a marker of poor fetal growth or suboptimal intrauterine conditions associated with hypertension risk later in life. View on Web

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Eano-Euracan-Sno Guidelines on Circumscribed Astrocytic GLIOMAS, Glioneuronal and Neuronaltumors

alexandrossfakianakis shared this article with you from Inoreader Eano-Euracan-Sno Guidelines on Circumscribed Astrocytic GLIOMAS, Glioneuronal and Neuronaltumors via Neuro-Oncology Advance Access Abstract In the new WHO 2021 Classification of CNS Tumors the chapter "Circumscribed astrocytic gliomas, glioneuronal and neuronal tumors" encompasses several different rare tumor entities, which occur more frequently in children, adolescents and young adults. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is low particularly for adult patients, and draw recommendations accordingly. Tumor diagnosis, based on WHO 2021, is primarily performed using conventional histological techniques; however, molecular workup is important for differential diagnosis, in particular DNA methylation profiling for the definitive classification of histologically unresolved cases. Molecular factors are increasingly of prognostic and predictive importance. MRI finding are non specific, but for some tumors are characteristic and suggestive. Gross total resection, when feasible, is the most important treatment in terms of prolonging survival and achieving long-term seizure control. Conformal radiotherapy should be considered in grade 3 and incompletely resected grade 2 tumors. In recurrent tumors reoperation and radiotherapy, including stereotactic radiotherapy, can be useful. Targeted therapies may be used in selected patients: BRAF and MEK inhibitors in pilocytic astrocytomas, pleomorphic xanthoastrocytomas, and gangliogliomas when BRAF altered, and mTOR inhibitor everolimus in subependymal giant cells astrocytomas .Sequencing to identify molecular targets is advocated for diagnostic clarification and to direct potential targeted therapies. View on Web

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Facial nerve palsy: Narrative review on the importance of the eye and its assessment

alexandrossfakianakis shared this article with you from Inoreader Facial nerve palsy: Narrative review on the importance of the eye and its assessment via Head & Neck Abstract New solutions are emerging that address specific facial regions in facial nerve palsy (FNP). However the most dreaded consequence of FNP is paralytic lagophthalmos threatening the eye. A way to prioritize these regions is thus required. A review of the literature is conduced to capture the current concepts in evaluating FNP. Overall, patients are assessed from three perspectives: from the clinician's perspective using validated clinician-based grading instruments, from patient's perspective based on FNP-specific patient-reported outcome measures, and from the perspective of the layperson. The existing tools however provide limited information regarding the relative importance of different regions of the face. The eye appears to be an area of great concern for the patient where most surgical therapies are directed at. Addressing ocular problems in FNP carry a high priority but this is not clearly reflected by the standard systems. View on Web

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Cross-platform analysis reveals cellular and molecular landscape of glioblastoma invasion

alexandrossfakianakis shared this article with you from Inoreader Cross-platform analysis reveals cellular and molecular landscape of glioblastoma invasion via Neuro-Oncology Advance Access Abstract Background Improved treatment of glioblastoma (GBM) needs to address tumor invasion, a hallmark of the disease that remains poorly understood. In this study, we profiled GBM invasion through integrative analysis of histological and single-cell RNA sequencing (scRNA-seq) data from ten patients. Methods Human histology samples, patient-derived xenograft mouse histology samples, and scRNA-seq data were collected from ten GBM patients. Tumor invasion was characterized and quantified at the phenotypic level using H&E and Ki-67 histology stains. Crystallin alpha B (CRYAB) and CD44 were identified as regulators of tumor invasion from scRNA-seq transcriptomic data and validated in vitro, in vivo, and in a mouse GBM resection model. Results At the cellular level, we found that invasive GBM are less dense and proliferative than their non-invasive counterparts. At the molecular level, we identified unique transcriptomic features that significantly contribute to GBM invasion. Specifically, we found that CRYAB significantly contributes to post-operative recurrence and is highly co-expressed with CD44 in invasive GBM samples. Conclusions Collectively, our analysis identifies differentially expressed features between invasive and nodular GBM, and describes a novel relationship between CRYAB and CD44 that contributes to tumor invasiveness, establishing a cellular and molecular landscape of GBM invasion. View on Web

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Genetic predisposition & evolutionary traces of pediatric cancer risk: A prospective 5-year population-based genome sequencing study of children with CNS tumors

alexandrossfakianakis shared this article with you from Inoreader Genetic predisposition & evolutionary traces of pediatric cancer risk: A prospective 5-year population-based genome sequencing study of children with CNS tumors via Neuro-Oncology Advance Access Abstract Background The etiology of central nervous system (CNS) tumors in children is largely unknown and population-based studies of genetic predisposition are lacking. Methods In this prospective, population-based study, we performed germline whole-genome sequencing in 128 children with CNS tumors, supplemented by a systematic pedigree analysis covering 3,543 close relatives. Results Thirteen children (10%) harbored pathogenic variants in known cancer genes. These children were more likely to have medulloblastoma (OR 5.9, CI 1.6-21.2) and develop metasynchronous CNS tumors (p=0.01). Similar carrier frequencies were seen among children with low-grade glioma (12.8%) and high-grade tumors (12.2%). Next, considering the high mortality of childhood CNS tumors throughout most of human evolution, we explored known pediatric-onset cancer genes, showing that they are more evolutionarily constrained than genes associated with risk of adult-onset malignancies (p=5e-4) and all other genes (p=5e-17). Based on this observation, we expanded our analysis to 2 986 genes exhibiting high evolutionary constraint in 141 456 humans. This analysis identified eight directly causative loss-of-functions variants, and showed a dose-response association between degree of constraint and likelihood of pathogenicity - raising the question of the role of other highly constrained gene alterations detected. Conclusions ∽10% of pediatric CNS tumors can be attributed to rare variants in known cancer genes. Genes associated with high risk of childhood cancer show evolutionary evidence of constraint. View on Web

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