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Neonatology 2021The diagnosis of neonatal meningitis often rests on microscopic and biochemical findings in the cerebrospinal fluid (CSF). There is ongoing uncertainty about age-related...
BACKGROUND
The diagnosis of neonatal meningitis often rests on microscopic and biochemical findings in the cerebrospinal fluid (CSF). There is ongoing uncertainty about age-related normal values for CSF findings in neonates, and many previous studies have included infants in whom antibiotics were administered before lumbar puncture or in whom viral meningitis was not excluded.
METHODS
A systematic search was done using MEDLINE and EMBASE to identify original studies which investigated CSF normal values in either healthy neonates or febrile neonates in whom bacterial and viral meningitis were reliably excluded.
RESULTS
We identified seven studies investigating 270 term and 96 preterm neonates. There were minimal differences between preterm and term neonates in the CSF white blood cell (WBC) count and glucose concentration. In contrast, the CSF neutrophil count and protein concentration were influenced by gestational and chronological age. In the four studies that reported individual patient data, in 95% of cases the CSF WBC count was <12 cells/μL in preterm and <10 cells/μL in term neonates, the neutrophil count was <16 and 8 cells/μL, and the protein concentration was <210 and 110 mg/dL, respectively.
CONCLUSION
The normal range for CSF parameters in neonates is different to that in older infants, and some parameters are influenced by gestational and chronological age. CSF parameters alone are not sufficiently reliable to exclude meningitis.
Topics: Aged; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Leukocyte Count; Meningitis; Reference Values; Retrospective Studies; Spinal Puncture
PubMed: 34818234
DOI: 10.1159/000517630 -
Trends in Immunology Apr 2023Reinvigorating the function of exhausted CD8 T cells during chronic viral infection and cancer is a major goal of current immunotherapy regimens. Here, we discuss recent... (Review)
Review
Reinvigorating the function of exhausted CD8 T cells during chronic viral infection and cancer is a major goal of current immunotherapy regimens. Here, we discuss recent advances in our understanding of exhausted CD8 T cell heterogeneity as well as the potential differentiation trajectories that exhausted T cells follow during chronic infection and/or cancer. We highlight surmounting evidence suggesting that some T cell clones are divergent in nature and can develop into either terminally differentiated effector or exhausted CD8 T cells. Lastly, we consider the potential therapeutic implications of such a bifurcation model of CD8 T cell differentiation, including the intriguing hypothesis that redirecting progenitor CD8 T cell differentiation along an effector pathway may serve as a novel approach to mitigate T cell exhaustion.
Topics: Humans; CD8-Positive T-Lymphocytes; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Cell Differentiation; Neoplasms
PubMed: 36907685
DOI: 10.1016/j.it.2023.02.006 -
No Shinkei Geka. Neurological Surgery Sep 2022Viral central nervous system(CNS)infections due to direct viral infection in the CNS include encephalitis/myelitis and meningitis. Acute encephalopathy is a CNS disorder...
Viral central nervous system(CNS)infections due to direct viral infection in the CNS include encephalitis/myelitis and meningitis. Acute encephalopathy is a CNS disorder that is mainly associated with viral respiratory infections. This article outlines herpes encephalitis, poliomyelitis, enterovirus A71 brainstem encephalitis/myelitis, and enterovirus D68 paralytic myelitis as acute encephalitis/myelitis, enteroviral meningitis and mumps meningitis as acute viral meningitis, and influenza encephalopathy and HHV-6 encephalopathy as acute encephalopathy.
Topics: Encephalitis; Enterovirus Infections; Humans; Meningitis; Myelitis
PubMed: 36128809
DOI: 10.11477/mf.1436204653 -
Nature Immunology Jul 2019Progenitor-like CD8 T cells mediate long-term immunity to chronic infection and cancer and respond potently to immune checkpoint blockade. These cells share...
Progenitor-like CD8 T cells mediate long-term immunity to chronic infection and cancer and respond potently to immune checkpoint blockade. These cells share transcriptional regulators with memory precursor cells, including T cell-specific transcription factor 1 (TCF1), but it is unclear whether they adopt distinct programs to adapt to the immunosuppressive environment. By comparing the single-cell transcriptomes and epigenetic profiles of CD8 T cells responding to acute and chronic viral infections, we found that progenitor-like CD8 T cells became distinct from memory precursor cells before the peak of the T cell response. We discovered a coexpression gene module containing Tox that exhibited higher transcriptional activity associated with more abundant active histone marks in progenitor-like cells than memory precursor cells. Moreover, thymocyte selection-associated high mobility group box protein TOX (TOX) promoted the persistence of antiviral CD8 T cells and was required for the programming of progenitor-like CD8 T cells. Thus, long-term CD8 T cell immunity to chronic viral infection requires unique transcriptional and epigenetic programs associated with the transcription factor TOX.
Topics: Animals; Biomarkers; CD8-Positive T-Lymphocytes; Chromatin Immunoprecipitation; Epigenesis, Genetic; Gene Expression Profiling; Gene Expression Regulation; High-Throughput Nucleotide Sequencing; Homeodomain Proteins; Host-Pathogen Interactions; Immunologic Memory; Infections; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice; Single-Cell Analysis; Time Factors; Transcriptome
PubMed: 31209400
DOI: 10.1038/s41590-019-0403-4 -
Molecular Cell Jun 2021CD8 T cells play an essential role in defense against viral and bacterial infections and in tumor immunity. Deciphering T cell loss of functionality is complicated by...
CD8 T cells play an essential role in defense against viral and bacterial infections and in tumor immunity. Deciphering T cell loss of functionality is complicated by the conspicuous heterogeneity of CD8 T cell states described across experimental and clinical settings. By carrying out a unified analysis of over 300 assay for transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencing (RNA-seq) experiments from 12 studies of CD8 T cells in cancer and infection, we defined a shared differentiation trajectory toward dysfunction and its underlying transcriptional drivers and revealed a universal early bifurcation of functional and dysfunctional T cell states across models. Experimental dissection of acute and chronic viral infection using single-cell ATAC (scATAC)-seq and allele-specific single-cell RNA (scRNA)-seq identified state-specific drivers and captured the emergence of similar TCF1 progenitor-like populations at an early branch point, at which functional and dysfunctional T cells diverge. Our atlas of CD8 T cell states will facilitate mechanistic studies of T cell immunity and translational efforts.
Topics: Acute Disease; Atlases as Topic; CD8-Positive T-Lymphocytes; Chromatin; Chronic Disease; Epigenesis, Genetic; Gene Expression Profiling; Gene Regulatory Networks; High-Throughput Nucleotide Sequencing; Humans; Immunity, Cellular; Lymphocyte Activation; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Neoplasms; Principal Component Analysis; Single-Cell Analysis; Transcription Factors; Transcription, Genetic; Transposases
PubMed: 33891860
DOI: 10.1016/j.molcel.2021.03.045 -
Nature Immunology Oct 2023Persistent exposure to antigen during chronic infection or cancer renders T cells dysfunctional. The molecular mechanisms regulating this state of exhaustion are thought...
Persistent exposure to antigen during chronic infection or cancer renders T cells dysfunctional. The molecular mechanisms regulating this state of exhaustion are thought to be common in infection and cancer, despite obvious differences in their microenvironments. Here we found that NFAT5, an NFAT family transcription factor that lacks an AP-1 docking site, was highly expressed in exhausted CD8 T cells in the context of chronic infections and tumors but was selectively required in tumor-induced CD8 T cell exhaustion. Overexpression of NFAT5 in CD8 T cells reduced tumor control, while deletion of NFAT5 improved tumor control by promoting the accumulation of tumor-specific CD8 T cells that had reduced expression of the exhaustion-associated proteins TOX and PD-1 and produced more cytokines, such as IFNɣ and TNF, than cells with wild-type levels of NFAT5, specifically in the precursor exhausted PD-1TCF1TIM-3CD8 T cell population. NFAT5 did not promote T cell exhaustion during chronic infection with clone 13 of lymphocytic choriomeningitis virus. Expression of NFAT5 was induced by TCR triggering, but its transcriptional activity was specific to the tumor microenvironment and required hyperosmolarity. Thus, NFAT5 promoted the exhaustion of CD8 T cells in a tumor-selective fashion.
Topics: Humans; Lymphocytic Choriomeningitis; Transcription Factors; CD8-Positive T-Lymphocytes; T-Cell Exhaustion; Persistent Infection; Tumor Microenvironment; Programmed Cell Death 1 Receptor; Lymphocytic choriomeningitis virus; Neoplasms
PubMed: 37709986
DOI: 10.1038/s41590-023-01614-x -
Frontiers in Public Health 2022The comprehensive epidemiology and impact of climate on viral meningitis (VM) in Kazakhstan are unknown. We aimed to study the incidence, in-hospital mortality and...
BACKGROUND
The comprehensive epidemiology and impact of climate on viral meningitis (VM) in Kazakhstan are unknown. We aimed to study the incidence, in-hospital mortality and influence of climatic indicators on VM from 2014 to 2019.
METHODS
Nationwide electronic healthcare records were used to explore this study. ICD-10 codes of VM, demographics, and hospital outcomes were evaluated using descriptive statistics and survival analysis.
RESULTS
During the 2014-2019 period, 10,251 patients with VM were admitted to the hospital. 51.35% of them were children, 57.85% were males, and 85.9% were from the urban population. Enteroviral meningitis was the main cause of VM in children. The incidence rate was 13 and 18 cases per 100,000 population in 2014 and 2019, respectively. Case fatality rate was higher in 2015 (2.3%) and 2017 (2.0%). The regression model showed 1°C increment in the daily average temperature might be associated with a 1.05-fold (95% CI 1.047-1.051) increase in the daily rate of VM cases, 1hPa increment in the average air pressure and 1% increment in the daily average humidity might contribute to a decrease in the daily rate of VM cases with IRRs of 0.997 (95% CI 0.995-0.998) and 0.982 (95% CI 0.981-0.983), respectively. In-hospital mortality was 35% higher in males compared to females. Patients residing in rural locations had a 2-fold higher risk of in-hospital death, compared to city residents. Elderly patients had a 14-fold higher risk of in-hospital mortality, compared to younger patients.
CONCLUSION
This is the first study in Kazakhstan investigating the epidemiology and impact of climate on VM using nationwide healthcare data. There was a tendency to decrease the incidence with outbreaks every 5 years, and mortality rates were higher for Russians and other ethnicities compared to Kazakhs, for males compared to females, for elder patients compared to younger patients, and for patients living in rural areas compared to city residents. The climatic parameters and the days of delay indicated a moderate interaction with the VM cases.
Topics: Male; Child; Female; Humans; Aged; Hospital Mortality; Kazakhstan; Meningitis, Viral; Incidence; Russia
PubMed: 36684964
DOI: 10.3389/fpubh.2022.1041135 -
Proceedings of the National Academy of... Oct 2023CD8 T cells play an essential role in antitumor immunity and chronic viral infections. Recent findings have delineated the differentiation pathway of CD8 T cells in...
CD8 T cells play an essential role in antitumor immunity and chronic viral infections. Recent findings have delineated the differentiation pathway of CD8 T cells in accordance with the progenitor-progeny relationship of TCF1 stem-like and Tim-3TCF1 more differentiated T cells. Here, we investigated the characteristics of stem-like and differentiated CD8 T cells isolated from several murine tumor models and human lung cancer samples in terms of phenotypic and transcriptional features as well as their location compared to virus-specific CD8 T cells in the chronically lymphocytic choriomeningitis virus (LCMV)-infected mice. We found that CD8 tumor-infiltrating lymphocytes (TILs) in both murine and human tumors exhibited overall similar phenotypic and transcriptional characteristics compared to corresponding subsets in the spleen of chronically infected mice. Moreover, stem-like CD8 TILs exclusively responded and produced effector-like progeny CD8 T cells in vivo after antigenic restimulation, confirming their lineage relationship and the proliferative potential of stem-like CD8 TILs. Most importantly, similar to the preferential localization of PD-1 stem-like CD8 T cells in T cell zones of the spleen during chronic LCMV infection, we found that the PD-1 stem-like CD8 TILs in lung cancer samples are preferentially located not in the tumor parenchyma but in tertiary lymphoid structures (TLSs). The stem-like CD8 T cells are present in TLSs located within and at the periphery of the tumor, as well as in TLSs closely adjacent to the tumor parenchyma. These findings suggest that TLSs provide a protective niche to support the quiescence and maintenance of stem-like CD8 T cells in the tumor.
Topics: Humans; Animals; Mice; Lymphocytic Choriomeningitis; Programmed Cell Death 1 Receptor; CD8-Positive T-Lymphocytes; Lymphocytic choriomeningitis virus; Persistent Infection; Lung Neoplasms; Mice, Inbred C57BL
PubMed: 37782797
DOI: 10.1073/pnas.2221985120