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The Lancet. Neurology Aug 2023Although meningitis is largely preventable, it still causes hundreds of thousands of deaths globally each year. WHO set ambitious goals to reduce meningitis cases by...
BACKGROUND
Although meningitis is largely preventable, it still causes hundreds of thousands of deaths globally each year. WHO set ambitious goals to reduce meningitis cases by 2030, and assessing trends in the global meningitis burden can help track progress and identify gaps in achieving these goals. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we aimed to assess incident cases and deaths due to acute infectious meningitis by aetiology and age from 1990 to 2019, for 204 countries and territories.
METHODS
We modelled meningitis mortality using vital registration, verbal autopsy, sample-based vital registration, and mortality surveillance data. Meningitis morbidity was modelled with a Bayesian compartmental model, using data from the published literature identified by a systematic review, as well as surveillance data, inpatient hospital admissions, health insurance claims, and cause-specific meningitis mortality estimates. For aetiology estimation, data from multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature studies were analysed by use of a network analysis model to estimate the proportion of meningitis deaths and cases attributable to the following aetiologies: Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, group B Streptococcus, Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Staphylococcus aureus, viruses, and a residual other pathogen category.
FINDINGS
In 2019, there were an estimated 236 000 deaths (95% uncertainty interval [UI] 204 000-277 000) and 2·51 million (2·11-2·99) incident cases due to meningitis globally. The burden was greatest in children younger than 5 years, with 112 000 deaths (87 400-145 000) and 1·28 million incident cases (0·947-1·71) in 2019. Age-standardised mortality rates decreased from 7·5 (6·6-8·4) per 100 000 population in 1990 to 3·3 (2·8-3·9) per 100 000 population in 2019. The highest proportion of total all-age meningitis deaths in 2019 was attributable to S pneumoniae (18·1% [17·1-19·2]), followed by N meningitidis (13·6% [12·7-14·4]) and K pneumoniae (12·2% [10·2-14·3]). Between 1990 and 2019, H influenzae showed the largest reduction in the number of deaths among children younger than 5 years (76·5% [69·5-81·8]), followed by N meningitidis (72·3% [64·4-78·5]) and viruses (58·2% [47·1-67·3]).
INTERPRETATION
Substantial progress has been made in reducing meningitis mortality over the past three decades. However, more meningitis-related deaths might be prevented by quickly scaling up immunisation and expanding access to health services. Further reduction in the global meningitis burden should be possible through low-cost multivalent vaccines, increased access to accurate and rapid diagnostic assays, enhanced surveillance, and early treatment.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Child; Humans; Global Burden of Disease; Bayes Theorem; Meningitis; Risk Factors; Global Health
PubMed: 37479374
DOI: 10.1016/S1474-4422(23)00195-3 -
Annals of Clinical and Translational... Jun 2024Fabry disease is caused by enzymatic defects in alpha-galactosidase A that leads to the accumulation of glycosphingolipids throughout the body, resulting in a...
OBJECTIVE
Fabry disease is caused by enzymatic defects in alpha-galactosidase A that leads to the accumulation of glycosphingolipids throughout the body, resulting in a multisystemic disorder. The most common neurological manifestations are neuropathic pain, autonomic nervous system dysfunction and strokes, but some rarer neurological manifestations exist. Among these, aseptic meningitis is a possible complication. Our objectives were to measure the prevalence of this complication in a cohort of patients with Fabry disease, and to describe its clinical features.
METHODS
We conducted a retrospective review of Fabry disease patients followed at our tertiary referral center between 1995 and September 2023 with at least one episode of meningitis, and performed a systematic review to identify similar published cases.
RESULTS
Four patients out of 107 (3.7%) had at least one episode of aseptic meningitis. Our systematic review identified 25 other observations. The median age of these 29 patients was 29.0 years, the median cerebrospinal fluid leukocyte count was 24 cells/mm3 with a predominance of lymphocytes in 64.7% of cases. In 82.8% of the patients, the diagnosis of Fabry disease was unknown before the meningitis. Large artery stenosis was present in 17.2% of patients and 57.1% of patients had a recent stroke concomitant with the meningitis. Several differential diagnoses were evoked, such as multiple sclerosis or central nervous system vasculitis.
INTERPRETATION
Our study suggests that Fabry disease should be considered as a cause of aseptic meningitis. The pathophysiological mechanisms underlying meningeal inflammation remain largely unknown but may reflect the dysregulation of pro-inflammatory signaling pathways.
Topics: Humans; Fabry Disease; Meningitis, Aseptic; Adult; Male; Female; Retrospective Studies; Middle Aged; Young Adult; Adolescent; Aged; Child
PubMed: 38717582
DOI: 10.1002/acn3.52043 -
Journal of Clinical Medicine Sep 2023Spheno-orbital meningiomas (SOMs) are rare tumors arising from the meninges surrounding the sphenoid bone and orbital structures. Surgical resection is the primary... (Review)
Review
BACKGROUND
Spheno-orbital meningiomas (SOMs) are rare tumors arising from the meninges surrounding the sphenoid bone and orbital structures. Surgical resection is the primary treatment approach for SOMs. Several surgical approaches have been described during the decades, including microsurgical transcranial (MTAs), endoscopic endonasal (EEAs), endoscopic transorbital (ETOAs), and combined approaches, and the choice of surgical approach remains a topic of debate.
PURPOSE
This systematic review and meta-analysis aim to compare the clinical and surgical outcomes of different surgical approaches used for the treatment of SOMs, discussing surgical techniques, outcomes, and factors influencing surgical decision making.
METHODS
A comprehensive literature review of the databases PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted for articles published on the role of surgery for the treatment of SOMs until 2023. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Meta-analysis was performed to estimate pooled event rates and assess heterogeneity. Fixed- and random-effects were used to assess 95% confidential intervals (CIs) of presenting symptoms, outcomes, and complications.
RESULTS
A total of 59 studies comprising 1903 patients were included in the systematic review and meta-analysis. Gross total resection (GTR) rates ranged from 23.5% for ETOAs to 59.8% for MTAs. Overall recurrence rate after surgery was 20.7%. Progression-free survival (PFS) rates at 5 and 10 years were 75.5% and 49.1%, respectively. Visual acuity and proptosis improvement rates were 57.5% and 79.3%, respectively. Postoperative cranial nerve (CN) focal deficits were observed in 20.6% of cases. The overall cerebro-spinal fluid (CSF) leak rate was 3.9%, and other complications occurred in 13.9% of cases. MTAs showed the highest GTR rates (59.8%, 95%CI = 49.5-70.2%; = 0.001) but were associated with increased CN deficits (21.0%, 95%CI = 14.5-27.6%). ETOAs had the lowest GTR rates (23.5%, 95%CI = 0.0-52.5%; = 0.001), while combined ETOA and EEA had the highest CSF leak rates (20.3%, 95%CI = 0.0-46.7%; = 0.551). ETOAs were associated with better proptosis improvement (79.4%, 95%CI = 57.3-100%; = 0.002), while anatomical class I lesions were associated with better visual acuity (71.5%, 95%CI = 63.7-79.4; = 0.003) and proptosis (60.1%, 95%CI = 38.0-82.2; = 0.001) recovery. No significant differences were found in PFS rates between surgical approaches.
CONCLUSION
Surgical treatment of SOMs aims to preserve visual function and improve proptosis. Different surgical approaches offer varying rates of GTR, complications, and functional outcomes. A multidisciplinary approach involving a skull base team is crucial for optimizing patient outcomes.
PubMed: 37762781
DOI: 10.3390/jcm12185840 -
Frontiers in Immunology 2023The utility of metagenomic next-generation sequencing (mNGS) in the diagnosis of tuberculous meningitis (TBM) remains uncertain. We performed a meta-analysis to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The utility of metagenomic next-generation sequencing (mNGS) in the diagnosis of tuberculous meningitis (TBM) remains uncertain. We performed a meta-analysis to comprehensively evaluate its diagnostic accuracy for the early diagnosis of TBM.
METHODS
English (PubMed, Medline, Web of Science, Cochrane Library, and Embase) and Chinese (CNKI, Wanfang, and CBM) databases were searched for relevant studies assessing the diagnostic accuracy of mNGS for TBM. Review Manager was used to evaluate the quality of the included studies, and Stata was used to perform the statistical analysis.
RESULTS
Of 495 relevant articles retrieved, eight studies involving 693 participants (348 with and 345 without TBM) met the inclusion criteria and were included in the meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver-operating characteristic curve of mNGS for diagnosing TBM were 62% (95% confidence interval [CI]: 0.46-0.76), 99% (95% CI: 0.94-1.00), 139.08 (95% CI: 8.54-2266), 0.38 (95% CI: 0.25-0.58), 364.89 (95% CI: 18.39-7239), and 0.97 (95% CI: 0.95-0.98), respectively.
CONCLUSIONS
mNGS showed good specificity but moderate sensitivity; therefore, a more sensitive test should be developed to assist in the diagnosis of TBM.
Topics: Humans; Tuberculosis, Meningeal; Sensitivity and Specificity; ROC Curve; High-Throughput Nucleotide Sequencing; Databases, Factual
PubMed: 37822937
DOI: 10.3389/fimmu.2023.1223675 -
Journal of Nanobiotechnology Aug 2023Lymph nodes targeted drug delivery is an attractive approach to improve cancer immunotherapy outcomes. Currently, the depth of understanding of afferent and efferent... (Review)
Review
Lymph nodes targeted drug delivery is an attractive approach to improve cancer immunotherapy outcomes. Currently, the depth of understanding of afferent and efferent arms in brain immunity reveals the potential clinical applications of lymph node targeted drug delivery in brain tumors, e.g., glioblastoma. In this work, we systematically reviewed the microenvironment of glioblastoma and its structure as a basis for potential immunotherapy, including the glial-lymphatic pathway for substance exchange, the lymphatic drainage pathway from meningeal lymphatic vessels to deep cervical lymph nodes that communicate intra- and extracranial immunity, and the interaction between the blood-brain barrier and effector T cells. Furthermore, the carriers designed for lymph nodes targeted drug delivery were comprehensively summarized. The challenges and opportunities in developing a lymph nodes targeted delivery strategy for glioblastoma using nanotechnology are included at the end.
Topics: Humans; Glioblastoma; Lymph Nodes; Brain Neoplasms; Brain; Drug Delivery Systems; Tumor Microenvironment
PubMed: 37542241
DOI: 10.1186/s12951-023-02011-0 -
Microorganisms Jul 2023Higher valency pneumococcal conjugate vaccines (PCV15 and PCV20) have been developed to address the disease burden of current non-vaccine serotypes. This review... (Review)
Review
Systematic Literature Review of the Epidemiological Characteristics of Pneumococcal Disease Caused by the Additional Serotypes Covered by the 20-Valent Pneumococcal Conjugate Vaccine.
Higher valency pneumococcal conjugate vaccines (PCV15 and PCV20) have been developed to address the disease burden of current non-vaccine serotypes. This review describes the epidemiological characteristics of serotypes beyond PCV13 (serotypes 8, 10A, 11A, 12F, 15B/C, 22F, and 33F; PCV20nonPCV13 serotypes). Peer-reviewed studies published between 1 January 2010 (the year PCV13 became available) and 18 August 2020 were systematically reviewed (PROSPERO number: CRD42021212875). Data describing serotype-specific outcomes on disease proportions, incidence, severity, and antimicrobial non-susceptibility were summarized for individual and aggregate PCV20nonPCV13 serotypes by age group and by type and duration of pediatric PCV immunization program. Of 1168 studies, 127 (11%) were included in the analysis. PCV20nonPCV13 serotypes accounted for 28% of invasive pneumococcal disease (IPD), although the most frequent serotypes differed between children (10A, 15B/C) and adults (8, 12F, 22F). In children, serotype 15B/C tended to be more frequently associated with pneumococcal meningitis and acute otitis media; in adults, serotype 8 was more frequently associated with pneumonia and serotype 12F with meningitis. Serotypes 10A and 15B/C in children and 11A and 15B/C in adults were often associated with severe IPD. Serotype 15B/C was also among the most frequently identified penicillin/macrolide non-susceptible PCV20nonPCV13 serotypes. These results could inform decision making about higher valency PCV choice and use.
PubMed: 37512988
DOI: 10.3390/microorganisms11071816 -
International Journal of Molecular... Aug 2023Giant arachnoid granulations (GAGs) are minimally investigated. Here, we systematically review the available data in published reports to better understand their... (Review)
Review
Giant arachnoid granulations (GAGs) are minimally investigated. Here, we systematically review the available data in published reports to better understand their etiologies, nomenclature, and clinical significance. In the literature, 195 GAGs have been documented in 169 persons of varied ages (range, 0.33 to 91 years; mean, 43 ± 20 years; 54% female). Prior reports depict intrasinus (i.e., dural venous sinus, DVS) (84%), extrasinus (i.e., diploic or calvarial) (15%), and mixed (1%) GAG types that exhibit pedunculated, sessile, or vermiform morphologies. GAG size ranged from 0.4 to 6 cm in maximum dimension (mean, 1.9 ± 1.1 cm) and encompassed symptomatic or non-symptomatic enlarged arachnoid granulations (≥1 cm) as well as symptomatic subcentimeter arachnoid granulations. A significant difference was identified in mean GAG size between sex (females, 1.78 cm; males, 3.39 cm; < 0.05). The signs and symptoms associated with GAGs varied and include headache (19%), sensory change(s) (11%), and intracranial hypertension (2%), among diverse and potentially serious sequelae. Notably, brain herniation was present within 38 GAGs (22%). Among treated individuals, subsets were managed medically (19 persons, 11%), surgically (15 persons, 9%), and/or by endovascular DVS stenting (7 persons, 4%). Histologic workup of 53 (27%) GAG cases depicted internal inflammation (3%), cystic change consistent with fluid accumulation (2%), venous thrombosis (1%), hemorrhage (1%), meningothelial hyperplasia (1%), lymphatic vascular proliferation (1%), and lymphatic vessel obliteration (1%). This review emphasizes heterogeneity in GAG subtypes, morphology, composite, location, symptomatology, and imaging presentations. Additional systematic investigations are needed to better elucidate the pathobiology, clinical effects, and optimal diagnostic and management strategies for enlarged and symptomatic arachnoid granulation subtypes, as different strategies and size thresholds are likely applicable for medical, interventional, and/or surgical treatment of these structures in distinct brain locations.
Topics: Male; Humans; Female; Brain; Clinical Relevance; Disease Progression; Headache; Vascular Diseases; Arachnoid
PubMed: 37629195
DOI: 10.3390/ijms241613014 -
Brain Communications 2024New treatments are needed to improve the prognosis of pneumococcal meningitis. We performed a systematic review on adjunctive treatments in animal models of pneumococcal... (Review)
Review
New treatments are needed to improve the prognosis of pneumococcal meningitis. We performed a systematic review on adjunctive treatments in animal models of pneumococcal meningitis in order to identify treatments with the most potential to progress to clinical trials. Studies testing therapy adjunctive to antibiotics in animal models of pneumococcal meningitis were included. A literature search was performed using Medline, Embase and Scopus for studies published from 1990 up to 17 February 2023. Two investigators screened studies for inclusion and independently extracted data. Treatment effect was assessed on the clinical parameters disease severity, hearing loss and cognitive impairment and the biological parameters inflammation, brain injury and bacterial load. Adjunctive treatments were evaluated by their effect on these outcomes and the quality, number and size of studies that investigated the treatments. Risk of bias was assessed with the SYRCLE risk of bias tool. A total of 58 of 2462 identified studies were included, which used 2703 experimental animals. Disease modelling was performed in rats (29 studies), rabbits (13 studies), mice (12 studies), gerbils (3 studies) or both rats and mice (1 study). Meningitis was induced by injection of into the subarachnoid space. Randomization of experimental groups was performed in 37 of 58 studies (64%) and 12 studies (12%) were investigator-blinded. Overall, 54 treatment regimens using 46 adjunctive drugs were evaluated: most commonly dexamethasone (16 studies), daptomycin (5 studies), complement component 5 (C5; 3 studies) antibody and Mn(III)tetrakis(4-benzoicacid)porphyrin chloride (MnTBAP; 3 studies). The most frequently evaluated outcome parameters were inflammation [32 studies (55%)] and brain injury [32 studies (55%)], followed by disease severity [30 studies (52%)], hearing loss [24 studies (41%)], bacterial load [18 studies (31%)] and cognitive impairment [9 studies (16%)]. Adjunctive therapy that improved clinical outcomes in multiple studies was dexamethasone (6 studies), C5 antibodies (3 studies) and daptomycin (3 studies). HMGB1 inhibitors, matrix metalloproteinase inhibitors, neurotrophins, antioxidants and paquinimod also improved clinical parameters but only in single or small studies. Evaluating the treatment effect of adjunctive therapy was complicated by study heterogeneity regarding the animal models used and outcomes reported. In conclusion, 24 of 54 treatment regimens (44%) tested improved clinically relevant outcomes in experimental pneumococcal meningitis but few were tested in multiple well-designed studies. The most promising new adjunctive treatments are with C5 antibodies or daptomycin, suggesting that these drugs could be tested in clinical trials.
PubMed: 38707710
DOI: 10.1093/braincomms/fcae131 -
Infectious Diseases and Therapy Nov 2023Streptococcus pneumoniae is the leading cause of meningitis, with a case fatality of up to about 50%. Children younger than 5 years are at greater risk for pneumococcal... (Review)
Review
INTRODUCTION
Streptococcus pneumoniae is the leading cause of meningitis, with a case fatality of up to about 50%. Children younger than 5 years are at greater risk for pneumococcal meningitis compared with other populations. It is of significant importance to provide a comprehensive understanding of the burden of pneumococcal meningitis among under-fives in the low pneumococcal conjugate vaccine (PCV) coverage period in China.
METHODS
A systematic review was conducted. We searched both English (PubMed, Ovid-EMBASE, Biosis, Web of Science, and Cochrane) and Chinese (CNKI, Wanfang, and ViP) databases for studies on bacterial meningitis in China published between January 1980 and July 2022. Ineligible studies were excluded based on study design and data integrity. Heterogeneity was assessed with I and estimates of bacterial meningitis morbidity and mortality were pooled using random-effects models. Subgroup analysis was conducted to trace the source of the heterogeneity and summarize average estimates.
RESULTS
A total of 13,082 studies were identified in the literature, and 56 studies were finally included for data analysis. The estimated incidence of pneumococcal meningitis was 2.10 cases per 100,000 children younger than 5 years each year (95% CI: 0.59-7.46), with a pooled case fatality rate of 24.59% (95%CI: 19.35-30.28%) in China. It was estimated that 1617.16 (95% CI: 454.35-5744.78) pneumococcal meningitis cases and 548.86 (95% CI: 474.80-627.62) deaths occurred among under-fives in China in 2020. Streptococcus pneumoniae played an important role in the etiology of confirmed bacterial meningitis cases, with a pooled proportion of 22.05% (95% CI: 17.83-26.27%). The most prevalent serotypes were 6B, 14, 19F, 19A, and 23F, which were preventable with a vaccine.
CONCLUSIONS
Pneumococcal meningitis remains one of the most important health problems among children younger than 5 years in China. Immunization programs should be promoted to avoid preventable cases and deaths.
PubMed: 37837523
DOI: 10.1007/s40121-023-00878-y -
Journal of Neurosurgery Dec 2023The relationship between patient and meningioma characteristics and hormone receptors (HRs) of progesterone, estrogen, and androgen remains poorly defined despite... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The relationship between patient and meningioma characteristics and hormone receptors (HRs) of progesterone, estrogen, and androgen remains poorly defined despite literature suggesting that meningiomas are sensitive to gonadal steroid hormones. Therefore, the authors sought to collect and compare data on this topic by performing a systematic review and meta-analysis of reported studies of HR status in meningiomas.
METHODS
A MEDLINE PubMed literature review conducted for articles published between January 1, 1951, and December 31, 2020, resulted in 634 unduplicated articles concerning meningiomas and HRs. There were 114 articles that met the criteria of detailed detection protocols for progesterone receptor (PR), estrogen receptor (ER), and/or androgen receptor (AR) using immunohistochemistry (IHC) or ligand-binding (LB) assays and simultaneous reporting of HR status with at least one variable among age, sex, histology, location, grade, or recurrence. Between-study heterogeneity and risk of bias were evaluated using graphical and statistical methods. The authors performed a multilevel meta-analysis using random-effects modeling on aggregated data (n = 4447) and individual participant data (n = 1363) with subgroup results summarized as pooled effects. A mixed-effects meta-regression using individual participant data was performed to analyze independently associated variables.
RESULTS
The 114 selected articles included data for 5810 patients with 6092 tumors analyzed to determine the expression of three HRs in human meningiomas: PRs, ARs, and ERs. The proportions of HR+ meningiomas were estimated to be 0.76 (95% CI 0.72-0.80) for PR+ and 0.50 (95% CI 0.33-0.66) for AR+ meningiomas. ER+ meningioma detection varied depending on the measurement method used and was 0.06 (95% CI 0.03-0.10) with IHC and 0.11 (95% CI 0.06-0.20) with LB assays. There were associations between age and PR and ER expression that varied between male and female patients. PR+ and AR+ were more common in female patients (OR 1.84, 95% CI 1.47-2.29 for PR and OR 4.16, 95% CI 1.62-10.68 for AR). Additionally, PR+ meningiomas were enriched in skull base locations (OR 1.89, 95% CI 1.03-3.48) and meningothelial histology (OR 1.86, 95% CI 1.23-2.81). A meta-regression showed that PR+ was independently associated with age (OR 1.11 95% CI 1.09-1.13; p < 0.0001) and WHO grade I tumors (OR 8.09, 95% CI 3.55-18.44; p < 0.0001). ER+ was negatively associated with meningothelial histology (OR 0.94, 95% CI 0.86-0.98; p = 0.044) and positively associated with convexity location (OR 1.12, 95% CI 1.05-1.18; p = 0.0003).
CONCLUSIONS
The association between HRs and meningioma features has been investigated but unexplained for decades. In this study the authors demonstrated that HR status has a strong association with known meningioma features, including WHO grade, age, female sex, histology, and anatomical location. Identifying these independent associations allows for a better understanding of meningioma heterogeneity and provides a foundation for revisiting targeted hormonal therapy in meningioma on the basis of proper patient stratification according to HR status.
Topics: Humans; Male; Female; Meningioma; Meningeal Neoplasms; Immunohistochemistry; Skull Base; Receptors, Estrogen; Gonadal Steroid Hormones
PubMed: 37243565
DOI: 10.3171/2023.3.JNS221838