Study of the inflammatory activating process in the early stage of Fusobacterium nucleatum infected PDLSCs

alexandrossfakianakis shared this article with you from Inoreader Study of the inflammatory activating process in the early stage of <i>Fusobacterium nucleatum</i> infected PDLSCs via International Journal of Oral Science - Issue International Journal of Oral Science, Published online: 08 February 2023; doi:10.1038/s41368-022-00213-0 Study of the inflammatory activating process in the early stage of Fusobacterium nucleatum infected PDLSCs View on Web

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Gaps in Depression Symptom Management for Patients With Head and Neck Cancer

alexandrossfakianakis shared this article with you from Inoreader Gaps in Depression Symptom Management for Patients With Head and Neck Cancer via The Laryngoscope We sought to understand practice patterns and identify care gaps within a large-scale depression screening program for patients with head and neck cancer. A high proportion of head and neck patients report depressive symptoms, though this triggers a referral in a small number of cases. These data highlight areas for improvement in depression screening care pathways. Objective To understand practice patterns and identify care gaps within a large-scale depression screening program for patients with head and neck cancer (HNC). Study Design Retrospective cohort study. Methods This was a population-based study of adults diagnosed with a HNC between January 2007 and October 2020. Each patient was observed from time of first symptom assessment until end of study date, or death. The exposure of interest was a positive depressive symptom screen on the Edmonton Symptom Assessment System (ESAS). Outcomes of interest included psychiatry/psychology assessment, social work referral, or palliative care assessment. Cause specific hazard models with a time-varying exposure were used to investigate the exposure-outcome relationships. Results Of 14,054 patients with HNC, 9016 (64.2%) reported depressive symptoms on at least one ESAS assessment. Within 60 days of first reporting depressive symptoms, 223 (2.7%) received a psychiatry assessment, 646 (7.9%) a social work referral, and 1131 (13.9%) a palliative care assessment. Rates of psychiatry/psychology assessment (HR 3.15 [95% CI 2.67–3.72]), social work referral (HR 1.83 [95% CI 1.64–2.02]), and palliative care assessment (HR 2.34 [95% CI 2.19–2.50]) were higher for those screening positive for depression. Certain patient populations were less likely to receive an assessment including the elderly, rural residents, and those without a prior psychiatric history. Conclusion A high proportion of head and neck patients report depressive symptoms, though this triggers a referral in a small number of cases. These data highlight areas for improvement in depression screening care pathways. Level of Evidence 3 Laryngoscope, 2023 View on Web

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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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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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