Features of cytomegalovirus DNAemia and virus‐specific T‐cell responses in allogeneic hematopoietic stem‐cell transplant recipients during prophylaxis with letermovir

alexandrossfakianakis shared this article with you from Inoreader Features of cytomegalovirus DNAemia and virus‐specific T‐cell responses in allogeneic hematopoietic stem‐cell transplant recipients during prophylaxis with letermovir via Transplant Infectious Disease Abstract Background There is scarce information on the natural kinetics of cytomegalovirus (CMV) DNAemia and dynamics of CMV-specific T-cell reconstitution in allogeneic hematopoietic transplant recipients (allo-HSCT) undergoing letermovir (LMV) prophylaxis. Methods Twelve adult CMV-seropositive high-risk recipients (median age, 53 years; 9 males/3 females) undergoing LMV prophylaxis and 13 non-LMV allo-HSCT controls (median age, 58 years; 7 males/6 females) were included. CMV DNAemia in plasma was monitored by real-time polymerase chain reaction. Preemptive antiviral therapy (PET) was administered upon detection of ≥1500 IU/ml. CMV-specific interferon-gamma (IFN-γ)-producing CD8+ and CD4+ T cells were enumerated by flow cytometry around days +30, +60, and +90 after allo-HSCT. Ex vivo experiments assessing of the potential effect of LMV on CMV-specific T-cell expansion in a single CMV-seropositive donor were also conducted. Results Five LMV patients (41.6%) developed CMV DNAemia that cleared spontaneously. Four patients (33.3%) developed CMV DNAemia after LMV cessation, of which two required PET. Nine non-LMV patients (69.2%) developed CMV DNAemia (five required PET). The percentage of LMV and non-LMV patients exhibiting detectable CMV-specific T-cell responses was comparable (7/10 vs. 10/13; p = .71). Nevertheless, median CMV-specific CD4+ and CD8+ T-cell counts were lower in LMV patients by days +60 (p = .006 and .02, respectively) and +90 (p = .08 and .02). Ex vivo, CMV-specific CD8+ T cells expanded to the same level either in the presence (19.8%) or in the absence of LMV (20.6%). Conclusions In our series, episodes of CMV DNAemia in LMV patients cleared spontaneously. A diminished degree of CMV-specific T-cell reconstitution in LMV patients compared to non-LMV patients was observed. View on Web

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Parvovirus B19 infection in pediatric allogeneic hematopoietic cell transplantation – Single‐center experience and review

alexandrossfakianakis shared this article with you from Inoreader Parvovirus B19 infection in pediatric allogeneic hematopoietic cell transplantation – Single‐center experience and review via Transplant Infectious Disease Abstract Background Parvovirus B19 (B19V) infection following pediatric hematopoietic cell transplantation (HCT) is a rare complication and available data is scarce. Therefore, we present the experience with B19V Infection in allogeneic pediatric HCT recipients at our transplant center together with a systematic review of the literature. Methods Pediatric HCT patients with Parvovirus B19 infection treated at the University Children's Hospital Münster between 1999 and 2021 were retrospectively identified and clinical data were analyzed. Additionally, a systematic MEDLINE search to identify relevant articles was performed. Results We identified three out of 445 patients (0.6%) with B19V infection post-transplantation. B19V infection occurred in combination with other complications like Graft-versus-Host disease, additional infections, or autoimmune-mediated hemolysis potentially triggered by B19V. In one patient these complications lead to a fatal outcome. The review of the literature showed considerable morbidity of B19V infection with the potential for life-threatening complications. Most patients were treated by red blood cell transfusion and intravenous immunoglobulins (IVIG) with a high succession rate. Conclusion Symptomatic B19V infection following HCT remains a rare but potentially challenging complication. A causal antiviral therapy does not exist as well as general recommendations on dosage and duration of IVIG therapy. Despite this, most patients are treated successfully with these measures. Additionally, transmission via blood or stem cell products is also rare and no general recommendations on B19V screenings exist. View on Web

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Genomic profiling and prognostic factors of H3 K27M‐mutant spinal cord diffuse glioma

alexandrossfakianakis shared this article with you from Inoreader Genomic profiling and prognostic factors of H3 K27M‐mutant spinal cord diffuse glioma via Brain Pathology In a large cohort (n=77), we characterized the molecular, clinicopathological, and prognostic characteristics of H3 K27M-mutant spinal cord diffuse glioma. ATRX mutation, CDK6 amplification, RB pathway alteration, a higher number of Copy number variant (CNV) events, chromosome (Chr) 9p deletion, and Chr 10p deletion is associated with worse survival. Glioblastoma histological type and a high Ki-67 index (>10%) are associated with a worse prognosis. Interestingly, the histological type, an independent prognostic factor in multivariate Cox regression, can stratify molecular features of H3 K27M-mutant spinal cord glioma, including the RB pathway and PI3K pathway. Abstract H3 K27-altered diffuse midline glioma is a highly lethal pediatric-type tumor without efficacious treatments. Recent findings have highlighted the heterogeneity among diffuse midline gliomas with different locations and ages. Compared to tumors located in the brain stem and thalamus, the molecular and clinicopathological features of H3 K27-altered spinal cord glioma are still largely elusive, thus hindering the accurate management of patients. Here we aimed to characterize the clinicopathological and molecular features of H3 K27M-mutant spinal cord glioma in 77 consecutive cases. We found that the H3 K27M-mutant spinal cord glioma, with a median age of 35 years old, had a significantly better prognosis than H3 K27M-mutant brain tumors. We noticed a molecular heterogeneity of H3 K27M-mutant spinal cord astrocytoma via targeted sequencing with 34 cases. TP53 mutation which occurred in 58.8% of cases is mutually exclusive with PPM1D (26%) and NF1 (44%) mutation s. The TP53-mutant cases had a significantly higher number of copy number variants (CNV) and a marginally higher proportion of pediatric patients (age at diagnosis <18 years old, p = 0.056). Cox regression and Kaplan–Meier curve analysis showed that the higher number of CNV events (≥3), chromosome (Chr) 9p deletion, Chr 10p deletion, ATRX mutation, CDK6 amplification, and retinoblastoma protein (RB) pathway alteration are associated with worse survival. Cox regression analysis with clinicopathological features showed that glioblastoma histological type and a high Ki-67 index (>10%) are associated with a worse prognosis. Interestingly, the histological type, an independent prognostic factor in multivariate Cox regression, can also stratify molecular features of H3 K27M-mutant spinal cord glioma, including the RB pathway, KRAS/PI3K pathway, and chromosome arms CNV. In conclusion, although all H3 K27M-mutant spinal cord d iffuse glioma were diagnosed as WHO Grade 4, the histological type, molecular features representing chromatin instability, and molecular alterations associated with accelerated cell proliferative activity should not be ignored in clinical management. View on Web

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Adjuvant Radiation and Survival Following Surgical Resection of Sinonasal Adenocarcinoma

alexandrossfakianakis shared this article with you from Inoreader Adjuvant Radiation and Survival Following Surgical Resection of Sinonasal Adenocarcinoma via The Laryngoscope Sinonasal adenocarcinoma is a rare primary malignancy treated with surgical resection with or without adjuvant radiotherapy. In this study, we saw that radiation therapy may not have an attributable survival benefit. Objectives This study aims to investigate the utility of adjuvant radiation in patients who undergo surgical resection for the management of node-negative sinonasal adenocarcinoma (SNAC). Study Design Retrospective database review. Methods The 2004–2016 National Cancer Data Base (NCDB) was used to extract patients with surgically resected node-negative SNAC. Kaplan–Meier survival analysis and Cox-Proportional Hazards Modelling were used to analyze the impact of adjuvant radiation on overall survival (OS) following surgery. Results 349 patients with SNAC underwent surgical resection. Of these patients, 154 (44.1%) received adjuvant radiotherapy (RT). Although there was no significant difference in race, age, or sex of those receiving RT, those receiving RT have more advanced diseases and are more likely to have positive margins. Kaplan Meier analysis showed no significant difference in 5-year OS in patient who received adjuvant RT in comparison to those who underwent surgical resection alone (65.7% vs. 72.6%, respectively; p = 0.378). In addition, when looking at only patients with positive margins, 5-year OS still did not have a significant difference (73.8% vs. 61.6%, respectively; p = 0.101). Only patients with clinical AJCC T4 showed a statistically significant survival benefit with adjuvant RT (56.9% vs. 29.9%, respectively; p = 0.009). Conclusions Adjuvant RT does not appear to provide a significant survival benefit in patients with resected SNAC, with the exception of those with clinically AJCC T4 disease. Level of Evidence 4 Laryngoscope, 2023 View on Web

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Prevalence of Apical Periodontitis in Patients with Autoimmune Diseases: A Case Control Study

alexandrossfakianakis shared this article with you from Inoreader Prevalence of Apical Periodontitis in Patients with Autoimmune Diseases: A Case Control Study via International Endodontic Journal Abstract Aim The purpose of this case-control study was to compare the prevalence of Apical Periodontitis (AP) in patients affected by Autoimmune Disorders (AD) [Inflammatory Bowel Disease (IBD), Rheumatoid Arthritis (RA), and Psoriasis (Ps)] with the prevalence of AP in subjects without AD. The prevalences of AP in patients taking biologic medications, conventional medications and no medication were also compared. Methodology 89 patients (2,145 teeth) with AD were investigated and the control group included 89 patients (2,329 teeth) with no systemic diseases. Full dental panoramic tomograms were used to determine the periapical status of the teeth. Additional variables investigated included patient's socio-demographic characteristics, medications taken by AD patients, the Decayed, Missing, and Filled Teeth (DMFT) index. The chi-square test and logistic regression analysis were used to evaluate the correlation between AD and AP. P-values lower than 0.05 were considered to be statistically significant. Results The prevalence of AP was 89.9% in AD patients and 74.2% in control subjects (odds ratio [OR]=3.75, p=0.015). The DMFT score was found to be significantly higher in the AD group (p=0.004). Patients with RA had the highest risk of being affected by AP, whereas those with IBD had the lowest risk. Multiple binary logistic regression analysis indicated that the teeth of AD patients who were not taking any medication or were being treated with biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) had a higher risk of being affected by AP than did the teeth of the control subjects (OR=1.42 and OR=2.03 respectively; p=0.010). The teeth of patients taking conventional DMARDs (cDMARDs) were less affected by AP compared with those of patients taking bDMARDs. Conclusions Patients with AD, whether treated or not with biologic medications, showed a higher prevalence of AP than did those in the control group. The DMFT index score, which was higher in AD patients compared with controls was identified as a significant predictor of AP prevalence. View on Web

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Estimating the effect of physical activity on cognitive function within the UK Biobank cohort

alexandrossfakianakis shared this article with you from Inoreader Estimating the effect of physical activity on cognitive function within the UK Biobank cohort via International Journal of Epidemiology - Advance Access Abstract Background Physical activity (PA) has been associated with benefits for cognitive function (CF), but previous estimates of the strength of this relationship may have been biased due to limitations in statistical modelling practices that are common among observational studies. We aimed to address this by using a rigorously constructed conceptual causal model to guide an empirical analysis estimating the effect of PA on CF in the UK Biobank cohort of middle-aged and older adults. Methods This study analysed a subsample of 334 227 adults from the UK Biobank prospective cohort study. PA was measured subjectively by self-report and by device using accelerometry, and CF was measured using objective cognitive tests. Composite CF measures were derived to represent general and domain-specific performance. Effect coefficients were estimated using regression models, adjusting for a wide range of confounders specified by the assumed caus al model, including genetic risk factors, and relevant health, sociodemographic and behavioural variables from across the lifespan. Results Results indicated very small effect sizes (standardized mean difference estimates all <0.01) of inconsistent direction, for both cross-sectional and longitudinal analyses. Conclusions The expected protective effect of PA on CF was not observed. This may reflect selection bias within UK Biobank, or the relatively young age of the sample at follow-up. View on Web

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Monkeypox keratoconjunctivitis with associated Wessley immune ring in an immunocompetent patient

alexandrossfakianakis shared this article with you from Inoreader Monkeypox keratoconjunctivitis with associated Wessley immune ring in an immunocompetent patient via Journal of Medical Virology ABSTRACT Monkeypox is a neglected zoonotic disease caused by Monkeypox virus (MPXV), a double-stranded DNA virus of the genus Orthopoxvirus. Here we present a case report of a 32-year-old man with MPXV infection who developed keratoconjunctivitis and Wessley immune ring with no identifiable cause other than ocular involvement by MPXV. We highlight the need of ophthalmologists exploring any ocular symptoms in MPXV-infected individuals. This article is protected by copyright. All rights reserved. View on Web

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Discovery of Isojacareubin as a covalent inhibitor of SARS‐CoV‐2 main protease using structural and experimental approaches

alexandrossfakianakis shared this article with you from Inoreader Discovery of Isojacareubin as a covalent inhibitor of SARS‐CoV‐2 main protease using structural and experimental approaches via Journal of Medical Virology Abstract The ongoing pandemic with the emergence of immune evasion potential and particularly the current omicron sub variants intensified the situation further. Although vaccine are available but the immune evasion capabilities of the recent variants demand further efficient therapeutic choices to control the SARS-CoV-2 pandemic. Hence, considering the necessity of the small molecule inhibitor we target the main protease (3CLpro) which is an appealing target for the development of anti-viral drugs against the SARS-CoV-2. High-throughput molecular in silico screening of South African natural compounds database (SANCDB) reported as Isojacareubin and Glabranin the potential inhibitors for main protease. The calculated docking scores were reported to be -8.47 kcal/mol and -8.03 kcal/mol respectively. Moreover, the structural-dynamic assessment reported that Isojacareubin in complex with 3CLpro exhibit more stable dynamic behaviour than Glabranin. Inhibition assay indicated that Isojacareubin could inhibit SARS-CoV-2 3CLpro in a time- and dose-dependent manner, with IC50 values of 16.00±1.35 μM (60-min incubation). Next, the covalent binding sites of Isojacareubin on SARS-CoV-2 3CLpro was identified by biomass spectrometry which reported that Isojacareubin can covalently bind to thiols or Cysteine through Michael addition. To evaluate the inactivation potency of Isojacareubin, the inactivation kinetics was further investigated. The inactivation kinetic curves were plotted according to various concentrations with gradient-ascending incubation times. The K I value of Isojacareubin was determined as 30.71 μM, while the K inact value was calculated as 0.054 min-1. These results suggest that Isojacareubin is a covalent inhibitor of SARS-CoV-2 3CLpro. This article is protected by copyright. All rights reserved. View on Web

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Characteristics of Adults Undergoing Soft Tissue and Orthognathic Surgery for Obstructive Sleep Apnea

alexandrossfakianakis shared this article with you from Inoreader Characteristics of Adults Undergoing Soft Tissue and Orthognathic Surgery for Obstructive Sleep Apnea via The Laryngoscope Of those with obstructive sleep apnea, unique clinical and demographic characteristics were identified in those who underwent soft tissue and orthognathic sleep surgery. Trends in palate-related surgery, as well as the proportion that was female, were examined over time. Objective To identify clinical and demographic characteristics of adults with obstructive sleep apnea (OSA) undergoing soft tissue and orthognathic sleep surgery, assess temporal trends in surgery type and proportion of women undergoing surgery, and provide clinical perspective before wide-spread implementation of hypoglossal nerve stimulation (HGNS). Methods In a retrospective cohort study, adults diagnosed with OSA from 2009 to 2016 were identified in a large integrated healthcare system. Characteristics between cohort members who did and did not undergo sleep surgeries were compared. Multivariable logistic regression models examined associations of different characteristics with whether surgery was performed. Results Of 172,216 adults with OSA, 2,262 (1.3%) underwent sleep surgery during 2009–2017. The most common sleep surgery was palate surgery (56.9%), which decreased proportionately over time. In multivariable analysis, older age and obesity were associated with lower odds of undergoing surgery. Those who underwent tonsillectomy and adenoidectomy were more likely to have larger tonsils and not require additional surgery, whereas tongue reduction recipients were more likely to have severe OSA and require multiple surgery types. The proportion of women undergoing surgery increased over time (p < 0.001 from trend test). Conclusion Clinical and demographic characteristics associated with soft tissue and orthognathic sleep surgery were identified in a large adult cohort prior to widespread implementation of HGNS. An increase in sleep surgery among women and a decrease in palate surgery over time were observed. The findings provide clinical perspective on sleep surgery performed prior to implementation of HGNS and may inform future studies examining its associations with patient characteristics. Level of Evidence 3 Laryngoscope, 2023 View on Web

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α‐KG Up‐regulates Autophagic Activity in Peri‐implant Environment and Enhances Dental Implant Osseointegration in Osteoporotic Mice

alexandrossfakianakis shared this article with you from Inoreader α‐KG Up‐regulates Autophagic Activity in Peri‐implant Environment and Enhances Dental Implant Osseointegration in Osteoporotic Mice via Journal of Clinical Periodontology Abstract Aim The osseointegration of dental implants is impaired among patients with osteoporosis, leading to significantly higher failure rate. This study set out to investigate the potential effects of alpha-ketoglutarate (α-KG) on implant osseointegration in an osteoporotic mouse model. Material and Methods Female C57BL/6 mice received ovariectomy and bilateral first maxillary molars extraction at the age of seven weeks. Dental implants were inserted eight weeks after tooth extraction. In one of the groups, α-KG was administered via drinking water throughout the experiment period. Specimens were collected on post-implant day (PID) 3, 7, 14, and 21 for micro-CT, histological and immunohistochemical analyses. At the same time, bone marrow-derived mesenchymal stem cells (BMMSCs) treated with α-KG were interrogated for osteogenic differentiation, autophagic activity, and apoptosis. Results α-KG supplement in drinking water resulted in enhanced dental implant osseointegration in ovariectomized mice, with upregulated osteogenic and autophagic activity and downregulated osteoclast differentiation and cell apoptosis. α-KG treated BMMSCs demonstrated enhanced activity in proliferation, survival, colony formation, osteogenic differentiation, as well as autophagic activity. Conclusions Systemic α-KG supplement effectively prevents the failure of dental implant osseointegration in mice under an osteoporotic state. This article is protected by copyright. All rights reserved. View on Web

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