Density of antibiotic use and infectious complications in pediatric allogeneic hematopoietic cell transplantationa

alexandrossfakianakis shared this article with you from Inoreader Density of antibiotic use and infectious complications in pediatric allogeneic hematopoietic cell transplantationa via Transplant Infectious Disease Abstract Background : Antibiotics, while an essential component of supportive care in allogeneic hematopoietic cell transplant (allo-HCT), can have adverse effects and select for antibiotic resistance. Understanding of patterns of use will inform antimicrobial stewardship (AMS) interventions. Methods : Retrospective, single center cohort of children undergoing first allo-HCT (n = 125). Antibiotic prescription and infection data were included from the date conditioning was commenced until 30 days post allo-HCT. Antibiotic use was reported as length of therapy (LOT) (number days a patient received an antibiotic) and days of therapy (DOT (aggregating all antibiotics prescribed per day). Infections were classified as microbiologically documented (MDI) or clinically documented infections (CDI). Results : At least one course of antibiotics was administered to 124 (99%) patients. The LOT was 636 per 1000 patient days and DOT was 959 per 1000 patient days. The median duration of cumulative antibiotic exposure per patient was 24 days (inter-quartile range (IQR) 20 – 30 days). There were 131 days of fever per 1000 patient days with patients febrile for a median of four days (IQR 1–7 days). Piperacillin-tazobactam was used for 116 (94%) of patients with a LOT of 532 per 1000 patient days. A total of 119 MDI episodes occurred in 74 (59%) patients, including blood stream infection in 30 (24%) and a proven/probable invasive fungal infection in four (3%). Conclusion : Pediatric HCT patients receive prolonged courses of broad-spectrum antibiotics relative to the frequency of fever and bacterial infections. This study has identified opportunities for AMS intervention to improve outcomes for our HCT patients. This article is protected by copyright. All rights reserved View on Web

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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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The Effect of Metformin on Vestibular Schwannoma Growth: A Systematic Review and Meta‐analysis

alexandrossfakianakis shared this article with you from Inoreader The Effect of Metformin on Vestibular Schwannoma Growth: A Systematic Review and Meta‐analysis via The Laryngoscope A systematic review and meta-analysis were performed to evaluate metformin's potential impact on VS growth. Metformin use may reduce the odds of VS growth. Objectives To systematically review and evaluate metformin's potential impact on vestibular schwannoma (VS) growth. Data Sources PubMed, Cochrane Library, and Embase. Review Methods A retrospective cohort study was performed on sporadic VS patients undergoing initial observation who had at least two magnetic resonance imaging studies. Patients were stratified by metformin use during the observation period. Primary endpoint was VS growth, defined as at least a 2 mm increase in diameter. Survival free of tumor growth was evaluated between groups. Systematic review and meta-analysis were performed to produce a pooled odds ratio [OR]. Study heterogeneity was assessed and post-hoc power analysis was performed. Results A total of 123 patients were included, of which 17% were taking metformin. Median patient age was 56.6 years (range, 25.1–84.5). There were no statistically significant differences between the groups. Survival analysis did not demonstrate a statistically significant difference in time to VS growth between groups (hazard ratio = 0.61, 95% confidence interval [CI] = 0.29–1.29). Furthermore, logistic regression analysis did not demonstrate a statistically significant difference between groups in the odds of VS growth (OR = 0.46, 95% CI = 0.17–1.27). Systematic review identified 3 studies. Meta-analysis suggested that metformin reduces the odds of developing VS growth (pooled OR = 0.45, 95% CI = 0.29–0.71). Studies demonstrated low between-study heterogeneity. Power analysis demonstrated a sample size of 220 patients with equal randomization would be required to prospectively identify a true difference with 80% powe r. Conclusions Metformin use may reduce the odds of VS growth. A randomized trial would be ideal to identify an unbiased estimate of metformin's effect on VS growth. 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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Usefulness of dried blood spot samples for monitoring hepatitis C treatment outcome and reinfection among people who inject drugs in a test‐and‐treat program

alexandrossfakianakis shared this article with you from Inoreader Usefulness of dried blood spot samples for monitoring hepatitis C treatment outcome and reinfection among people who inject drugs in a test‐and‐treat program via Journal of Medical Virology Abstract Background Dried blood spots (DBS) are a reliable tool to diagnose viremic HCV infection. We evaluated the clinical performance of a DBS-based molecular assay for the assessment of cure and reinfection after on-site treatment at a harm reduction centre (HRC). Genotyping from DBS samples was also assessed to discriminate reinfection from treatment failure. Methods People who inject drugs (PWID) from an ongoing microelimination pilot at the largest HRC in Barcelona were included in the study. HCV-RNA detection from DBS collected after treatment (with follow-up at 12, 36 and 60 weeks) was compared with a molecular point-of-care test using finger-stick blood (GeneXpert). Baseline and follow-up DBS samples were genotyped by NS5B sequencing or commercial real-time PCR. Results Among treated patients, 193 follow-up DBS samples were tested. The DBS-based assay showed 100% specificity (129/129), and sensitivity ranged from 84.4% to 96.1% according to different viral load cut-offs (from detectable to 3000 IU/mL). Sensitivity as test of cure (follow-up 12) ranged from 85.1 to 97.4%. Among the 64 patients with recurrent viremia, 10.9% had low viral loads (≤1000 IU/mL); HCV genotyping allowed us to classify 73.5% of viremic cases either as reinfection or as treatment failure. Conclusions DBS samples are useful to assess cure and differentiate reinfection from relapse after HCV antiviral treatment in the real world, facilitating decentralization of treatment and post-treatment follow-up in PWID. However, a fraction of patients presented with low viral loads, limiting viremia detection and genotyping in DBS and, therefore, repeat testing is recommended. This article is protected by copyright. All rights reserved. View on Web

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Autogenous dentin graft versus alloplastic graft combined with socket shield for pre-implant socket preservation: a split-mouth randomized clinical trial

alexandrossfakianakis shared this article with you from Inoreader Autogenous dentin graft versus alloplastic graft combined with socket shield for pre-implant socket preservation: a split-mouth randomized clinical trial via International Journal of Oral and Maxillofacial Surgery via MedWorm.com After tooth extraction, alveolar bone resorption and labial bone plate thinning occur due to the lack of periodontal ligaments. The socket shield method was developed to preserve the alveolar ridge. A split-mouth study was performed in which eight patients were treated using alloplast with socket shield on one side (alloplast group, control) and autogenous dentin graft with socket shield on the contralateral side (dentin group, test). After 3 months, a trephine bone core was collected from all sites and evaluated by histological, histomorphometric, and radiographic analysis. (Source: International Journal of Oral and Maxillofacial Surgery) View on Web

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