Molecular heterogeneity of pediatric choroid plexus carcinomas determines the distinctions in clinical course and prognosis

alexandrossfakianakis shared this article with you from Inoreader Molecular heterogeneity of pediatric choroid plexus carcinomas determines the distinctions in clinical course and prognosis via Neuro-Oncology Advance Access Abstract Background Choroid plexus carcinomas (CPCs) are rare aggressive pediatric tumors of the brain with no treatment standards. Genetic profiling of CPCs is often confined to possible association with Li–Fraumeni syndrome, though only about a half of CPCs develop from syndromic predispositions. Whole-chromosome gains and losses typical of CPCs reflect genomic instability of these tumors, but only partially explain the aggressive clinical course. Methods This retrospective study enrolled 25 pediatric patients with CPC, receiving treatment between January 2009 and June 2022. Molecular genetic testing was performed for 20 cases with available tumor tissue and encompassed mutational status, chromosomal aberrations and gene expression profiles. We analyzed several factors presumably influencing the outcomes, including molecular profiles and clinical parameters. The median follow-up constituted 5.2 years (absolute range 2.8–12.6 years ). Results All studied CPCs had smooth mutational profiles with the only recurrent event being TP53 variants, either germline or somatic, encountered in 13 cases. Unbalanced whole-chromosome aberrations, notably multiple monosomies, were highly typical. In seven tumors, chromosome losses were combined with complex genomic rearrangements: segmental gains and losses or signs of chromothripsis. This phenomenon was associated with extremely low 5-year survival: 20.0±17.9% vs. 85.7±13.2%; p=0.009. Transcriptomically, the cohort split into two polar clusters Ped_CPC1 and Ped_CPC2 differing by survival: 31.3±17.8% vs. 100%; p=0.012. Conclusion CPCs split into at least two molecular subtypes distinguished both genomically and transcriptomically. Clusterization of the tumors into Ped_CPC1 and Ped_CPC2 significantly correlates with survival. The distinct ion may prove relevant in clinical trials for dedicated and patient-oriented optimization of clinical protocols for these rare tumors. View on Web

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Impact of SARS-CoV-2 variants on inpatient clinical outcome

alexandrossfakianakis shared this article with you from Inoreader Impact of SARS-CoV-2 variants on inpatient clinical outcome via Clinical Infectious Diseases Advance Access Abstract Background Prior observation has shown differences in COVID-19 hospitalization risk between SARS-CoV-2 variants, but limited information describes hospitalization outcomes. Methods Inpatients with COVID-19 at five hospitals in the eastern United States were included if they had hypoxia, tachypnea, tachycardia, or fever, and SARS-CoV-2 variant data, determined from whole genome sequencing or local surveillance inference. Analyses were stratified by history of SARS-CoV-2 vaccination or infection. The average effect of SARS-CoV-2 variant on 28-day risk of severe disease, defined by advanced respiratory support needs, or death was evaluated using models weighted on propensity scores derived from baseline clinical features. Results Severe disease or death within 28 days occurred for 977 (29%) of 3,369 unvaccinated patients and 269 (22%) of 1,230 patients with history of vaccination or prior SARS-CoV-2 infection. Among unvac cinated patients, the relative risk of severe disease or death for Delta variant compared to ancestral lineages was 1.30 (95% confidence interval [CI] 1.11-1.49). Compared to Delta, this risk for Omicron patients was 0.72 (95% CI 0.59-0.88) and compared to ancestral lineages was 0.94 (95% CI 0.78-1.1). Among Omicron and Delta infections, patients with history of vaccination or prior SARS-CoV-2 infection had half the risk of severe disease or death (adjusted hazard ratio 0.40, 95% CI 0.30-0.54), but no significant outcome difference by variant. Conclusions Although risk of severe disease or death for unvaccinated inpatients with Omicron was lower than Delta, it was similar to ancestral lineages. Severe outcomes were less common in vaccinated inpatients, with no difference between Delta and Omicron infections. View on Web

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Errors of Interpretation - correcting the record on the comparative efficacy of surgical masks versus respirators

alexandrossfakianakis shared this article with you from Inoreader Errors of Interpretation - correcting the record on the comparative efficacy of surgical masks versus respirators via Clinical Infectious Diseases Advance Access View on Web

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Tuberculosis and the Risk of Ischemic Heart Disease: A Nationwide Cohort Study

alexandrossfakianakis shared this article with you from Inoreader Tuberculosis and the Risk of Ischemic Heart Disease: A Nationwide Cohort Study via Clinical Infectious Diseases Advance Access Abstract Background Little is known about the risk of ischemic heart disease (IHD) in tuberculosis (TB) survivors. Methods We performed a population-based retrospective cohort study using the Korean National Health Insurance Service database. TB survivors (n = 60,602) and their 1:1 age- and sex-matched controls (n = 60,602) were enrolled. Eligible participants were followed up from 1 year after their TB diagnosis to the date of an IHD event, date of deat h, or the end of the study period (December 31, 2018), whichever came first. The risk of IHD was estimated using a Cox proportional hazards regression, and stratified analyses were performed for related factors. Among IHD events, we additionally analyzed for myocardial infarction (MI). Results During a median of 3.9 years of follow-up, 2.7% of TB survivors (1,633/60,602) and 2.0% of the matched controls (1,228/60,602) developed IHD, and 0.6% of TB patients (341/60,602) and 0.4% of the matched controls (223/60,602) developed MI. The overall risk of developing IHD and MI was higher in TB patients (adjusted hazard [aHR] 1.21, 95% CI 1.12–1.32 for IHD and aHR 1.48, 95% CI 1.23–1.78 for MI) than in the matched controls. Stratified analyses showed that TB survivors have an increased risk of IHD and MI regardless of income, place of residence, smoking status, alcohol consumption, physical activity, body mass index, and Charlson comorbidity index. Conclusions TB surviv ors have a higher risk of IHD than matched controls. Strategies are needed to reduce the burden of IHD in TB survivors. View on Web

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Recommendation for imaging follow‐up strategy based on time‐specific disease failure for nasopharyngeal carcinoma

alexandrossfakianakis shared this article with you from Inoreader Recommendation for imaging follow‐up strategy based on time‐specific disease failure for nasopharyngeal carcinoma via Head & Neck Abstract Background To develop a common follow-up strategy for appropriate imaging examination at an appropriate time for nasopharyngeal carcinoma (NPC). Methods Independent prognostic factors were identified by Cox regression analysis, and a nomogram model was developed. Random survival forest (RSF) model was constructed to depict probability of disease failure during a 5-year follow-up and establish a reasonable risk-based follow-up strategy. Results The nomogram model finally categorized the patients into three risk groups. RSF model demonstrated distribution trends for local and regional recurrences, bone metastasis, liver metastasis, and lung metastasis of NPC. Adequate imaging at follow-up should be considered between 10 and 21 months for patients at moderate-risk of recurrence or metastasis and 7–36 months for those at high-risk. Conclusions The temporal distribution of incidence rates of recurrence or metastasis varied among different risk groups. We recommend implementing a focused and targeted imaging surveillance intervention at appropriate times to improve its efficiency and reduce costs. View on Web

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Tuberculosis treatment without rifampin in kidney/kidney–pancreas transplantation: A case series report

alexandrossfakianakis shared this article with you from Inoreader Tuberculosis treatment without rifampin in kidney/kidney–pancreas transplantation: A case series report via Transplant Infectious Disease Tuberculosis treatment without rifampin in kidney/kidney pancreas transplantation. Abstract Background The best approach to tuberculosis (TB) treatment in transplanted patients is still unknown. Current guidelines are based on evidence either extrapolated from other populations or observational. Rifampin-containing regimens have strong pharmacokinetic interactions with immunosuppressive regimens, with high rates of organ dysfunction and ∼20% mortality. This report describes the results obtained using non-rifampin-containing regimens to treat confirmed TB in adult patients with kidney/kidney–pancreas transplantation. Methods Retrospective data analysis from confirmed TB cases in adult kidney/kidney–pancreas transplant recipients (2006–2019), treated "de novo" with non-rifampin-containing regimens. Results Fifty-seven patients had confirmed TB. Thirty patients were treated "de novo" with non-rifampin-containing regimens. These patients' mean age was 49.24 (±11.50) years. Induction immunosuppression was used in 22 patients. Maintenance immunosuppression was tacrolimus–mycophenolate–steroids in 13 (43%), sirolimus–mycophenolate–steroids in 6 (20%), and other immunosuppressive regimens in 11 (36%). Belatacept was used in four patients. TB localizations: pulmonary 43%; disseminated 23%; extrapulmonary 33%. Twenty-seven (90%) patients completed treatment with isoniazid, ethambutol, and levofloxacin (12 months, 23; 9 months, 3; 6 months, 1); 12 of these patients also received pyrazinamide for the first 2 months and were cured with functioning grafts. One patient (3%) lost the graft while on treatment. Two patients (7%) died while on TB treatment. Median (range) follow-up after completion of TB treatment was 32 (8–150) months. No TB relapses were observed. Conclusions Results with non-rifampin-containing TB treatments in this case series were better (in terms of mortality and graft dysfunction) than those previously described with rifampin-containing regimens in transplanted patients. View on Web

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Acute‐phase response following one‐stage full‐mouth versus quadrant non‐surgical periodontal treatment in subjects with comorbid type 2 diabetes: A randomized clinical trial

alexandrossfakianakis shared this article with you from Inoreader Acute‐phase response following one‐stage full‐mouth versus quadrant non‐surgical periodontal treatment in subjects with comorbid type 2 diabetes: A randomized clinical trial via Journal of Clinical Periodontology Abstract Aim To compare the level of inflammatory markers and endothelial function 24 hours (Day1) and 90 days (Day90) after conventional quadrant-wise (Q-SRP) versus one-stage full-mouth scaling (FM-SRP) in patients affected by type 2 diabetes mellitus (T2DM). Methods Patients affected by periodontitis and T2DM were randomly allocated to receive FM-SRP or Q-SRP and followed up at Day1 and Day90. Serum samples, vital signs and flow-mediated dilation (FMD) parameters were collected at baseline, Day1 and Day90. Periodontal variables were collected at baseline and Day90. The primary outcome was the C-reactive Protein (CRP) concentration at Day1 after periodontal treatment. The Student t-test for independent samples was used for between-group comparisons (Mann Whitney U test for non-normal data), while the ANOVA with post-hoc Tukey tests (Kruskal Wallis and Dunn tests for non-normal data) were used for intragroup comparisons. Results 40 subjects were included. FM-SRP produced a significant increase in CRP and a significant reduction in FMD at Day1 compared to Q-SRP (p<0.05). The absolute change in HbA1c (mmol/mol) from baseline to Day90 was significantly improved in the Q-SRP (ΔHbA1c=-1.59 (SD=1.20)) compared to the FM-SRP group (ΔHbA1c=-0.8 (SD=0.95)) (p=0.04). Conclusions FM-SRP triggers a robust acute-phase response at 24 hours after treatment compared to Q-SRP. Such systemic acute perturbations may offset the benefic systemic effects of periodontal treatment in terms of HbA1c reduction and improvement in endothelial function in T2DM subjects. View on Web

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Long‐term impact of patients' compliance to peri‐implant maintenance therapy on the incidence of peri‐implant diseases: An 11‐year prospective follow‐up clinical study

alexandrossfakianakis shared this article with you from Inoreader Long‐term impact of patients' compliance to peri‐implant maintenance therapy on the incidence of peri‐implant diseases: An 11‐year prospective follow‐up clinical study via Clinical Implant Dentistry and Related Research Abstract Objective To prospectively evaluate the incidence of peri-implant diseases and the associated risk factors during 11 years of peri-implant maintenance therapy (PIMT). Material and Methods A sample of 80 partially edentulous individuals rehabilitated with dental implants was invited to participate in a PIMT program (T1—prior to entering the PIMT program). After 11 years, 51 individuals remained regularly or irregularly adherent to PIMT (T2—last recall after 11 years) and were classified as regular (RC; n = 27) or irregular (IC; n = 24) compliers. Data of interest were analyzed using univariate and multivariate logistic regression analyses. Results The incidence of peri-implant mucositis and peri-implantitis observed at T2 in the IC group (70.8% and 37.5%, respectively) were significantly higher than those observed in the RC group (37.0% and 11.1%, respectively). The incidence of peri-implant diseases was mostly attributable to potentially modifiable risk factors, as such: RC group—PM (p = 0.013); IC group—high plaque index (p < 0.001), irregular compliance (p < 0.001), the presence of PM (p = 0.015) and periodontitis (p < 0.039). Conclusion Regular compliance during PIMT had a strong effect in minimizing the incidence of peri-implant diseases. Increasing regular dental visits and improving oral hygiene would provide benefits for preventing peri-implant diseases. View on Web

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Detection and Monitoring of Circulating Tumor HPV DNA in HPV-Associated Sinonasal and Nasopharyngeal Cancers

alexandrossfakianakis shared this article with you from Inoreader Detection and Monitoring of Circulating Tumor HPV DNA in HPV-Associated Sinonasal and Nasopharyngeal Cancers via JAMA Otolaryngology–Head & Neck Surgery Online First This prospective observational study examines if circulating tumor human papillomavirus DNA can be used as an accurate measure of disease status at the time of diagnosis, throughout treatment, and during monitoring in human papillomavirus-associated sinonasal and nasopharyngeal squamous cell carcinomas. View on Web

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Exome Sequencing Expands the Genetic Diagnostic Spectrum for Pediatric Hearing Loss

alexandrossfakianakis shared this article with you from Inoreader Exome Sequencing Expands the Genetic Diagnostic Spectrum for Pediatric Hearing Loss via The Laryngoscope We describe the results of exome sequencing for genetic diagnosis of hearing loss among a clinically heterogeneous cohort of 218 pediatric patients. We found a higher diagnostic rate for unilateral hearing loss than previously reported as well as a significant number of syndromic forms of hearing loss. Based on these results, we advocate for expanded access to genetic testing for phenotypically diverse hearing loss patients. Objectives Genetic testing is the standard-of-care for diagnostic evaluation of bilateral, symmetric, sensorineural hearing loss (HL). We sought to determine the efficacy of a comprehensive genetic testing method, exome sequencing (ES), in a heterogeneous pediatric patient population with bilateral symmetric, bilateral asymmetric, and unilateral HL. Methods Trio-based ES was performed for pediatric patients with confirmed HL including those with symmetric, asymmetric, and unilateral HL. Results ES was completed for 218 probands. A genetic cause was identified for 31.2% of probands (n = 68). The diagnostic rate was 40.7% for bilateral HL, 23.1% for asymmetric HL, and 18.3% for unilateral HL, with syndromic diagnoses made in 20.8%, 33.3%, and 54.5% of cases in each group, respectively. Secondary or incidental findings were identified in 10 families (5.52%). Conclusion ES is an effective method for genetic diagnosis for HL including phenotypically diverse patients and allows the identification of secondary findings, discovery of deafness-causing genes, and the potential for efficient data re-analysis. Level of Evidence Level IV Laryngoscope, 2022 View on Web

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