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Child's Nervous System : ChNS :... Apr 2024We aimed to determine the safety and effectiveness of intraventricular antibiotics in neonates with meningitis and/or ventriculitis and analyze the quality of available... (Meta-Analysis)
Meta-Analysis
PURPOSE
We aimed to determine the safety and effectiveness of intraventricular antibiotics in neonates with meningitis and/or ventriculitis and analyze the quality of available evidence.
METHODS
DESIGN: Systematic review and meta-analysis.
DATA SOURCES
PubMed, EMBASE, LILACS, and SCOPUS up to 17 February 2023.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomized experimental and observational studies were included. The Cochrane methodology was used for systematic reviews.
RESULTS
Twenty-six observational studies and one randomized clinical trial involving 272 patients were included. The risk of bias in both pediatric and neurosurgical studies was high, and the quality of evidence was low (evidence level C). In the pediatric studies, no significant differences in mortality were found between intraventricular antibiotics and only systemic antibiotic [25.4% vs 16.1%, OR = 0.96 (0.42-2.24), P = 0.93]. However, when analyzing the minimum administered doses, we found a lower mortality when a minimum duration of 3 days for intraventricular antibiotics was used compared to only systemic antibiotic [4.3% vs 17%, OR = 0.22 (0.07-0.72), P = 0.01]. In the neurosurgical studies, the use of intraventricular antibiotics in ventriculitis generally results in a mortality of 5% and a morbidity of 25%, which is lower than that in cases where intraventricular antibiotics were not used, with an average mortality of 37.3% and a morbidity of 50%.
CONCLUSION
Considering the low quality of evidence in pediatric and neurosurgical studies, we can conclude with a low level of certainty that intraventricular antibiotics may not significantly impact mortality in neonatal meningitis and ventriculitis. However, reduced mortality was observed in cases treated with a minimum duration of 3 days of intraventricular antibiotic, particularly the multidrug-resistant or treatment-refractory infections. Higher-quality studies are needed to improve the quality of evidence and certainty regarding the use of intraventricular antibiotics for treating neonatal meningitis and ventriculitis.
Topics: Humans; Infant, Newborn; Anti-Bacterial Agents; Cerebral Ventriculitis; Meningitis; Randomized Controlled Trials as Topic
PubMed: 38015250
DOI: 10.1007/s00381-023-06240-4 -
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 -
Acta Neurochirurgica Oct 2023Meningiomas are the most common primary intracranial tumor. While the majority of meningiomas are benign, rarely they can metastasize extracranially. There is a need for...
BACKGROUND
Meningiomas are the most common primary intracranial tumor. While the majority of meningiomas are benign, rarely they can metastasize extracranially. There is a need for a more comprehensive review of these patients to improve our understanding of this rare phenomenon and its prevalence globally. Here we describe our institution's experience of patients presenting with metastatic meningiomas. We further perform a systematic review of the existing literature to explore common features of this rare manifestation of meningioma and review the efficacy of current treatments.
METHODS
We performed a retrospective clinical review of all adult patients with metastatic meningioma managed at our institution over the past 20 years, identifying 6 patients. We then performed a systematic review of cases of metastatic meningioma in the literature ranging from the years 1886 to 2022. A descriptive analysis was then conducted on the available data from 1979 onward, focusing on the grade and location of the primary tumor as well as the latency period to, and location of, the metastasis.
RESULTS
In total, we analyzed 155 cases. Fifty-four percent of patients initially presented with a primary meningioma located in the convexity. The most common site of metastasis was the lung. Risk factors associated with a shorter time to metastasis were male sex and a high initial grade of the tumor. Regarding treatment, the addition of chemotherapy was the most common adjunct to the standard management of surgery and radiotherapy. Despite an exhaustive review we were unable to identify effective treatments. The majority of published cases came from centers situated in high-income countries (84%) while only 16% came from lower- and middle-income countries.
CONCLUSIONS
Metastatic meningiomas pose a pertinent, and likely underestimated, clinical challenge within modern neurosurgery. To optimize management, timely identification of these patients is important. More research is needed to explore the mechanisms underlying these tumors to better guide the development of effective screening and management protocols. However, screening of each meningioma patient is not feasible, and at the heart of this challenge is the inability to control the primary disease. Ultimately, a consensus is needed as to how to correctly screen for and manage these patients; genomic and epigenomic approaches could hold the answer to finding druggable targets.
Topics: Adult; Female; Humans; Male; Brain Neoplasms; Meningeal Neoplasms; Meningioma; Retrospective Studies; Treatment Outcome
PubMed: 37491650
DOI: 10.1007/s00701-023-05687-3 -
The International Journal of... Jun 2024Central nervous system involvement by Brucella species is the most morbid form of brucellosis disease. Studies on neurobrucellosis are scarce and limited to case reports... (Meta-Analysis)
Meta-Analysis
PURPOSE
Central nervous system involvement by Brucella species is the most morbid form of brucellosis disease. Studies on neurobrucellosis are scarce and limited to case reports and series. Brucella is unable to infect or harm neurons without the assistance of monocytes. This raises the question of whether ceftriaxone-based regimens are effective.
METHODS
The primary aim of this study was to identify, evaluate, and summarize the findings of all relevant individual studies in the past 30 years to help better understand the disease. To achieve this, a broad systematic search was undertaken to identify all relevant records. Epidemiological and clinical features of the disease were assessed by the pooled analysis of descriptive studies. Through a meta-analysis, the treatment period duration was compared between the ceftriaxone-based and oral regimens using Standardized mean differences to measure effect size.
RESULTS
448 patients were included in the Meta-analyses from 5 studies. A moderate positive effect was found for ceftriaxone-based regimens over oral treatments, and there was a significant difference between these two groups (SMD 0.428, 95% CI -0.63 to -0.22, I 2 = 37.64). Neurobrucellosis has a different clinical picture in pediatric patients. The disease is less chronic in children. Fever, nausea and vomiting, fatigue, and abdominal pain were significantly more prevalent symptoms in children, and Convulsions, ascites, sensorineural hearing loss, and papilledema were significantly more prevalent signs in children than adults.
CONCLUSION
It is recommended to initiate the treatment of neurobrucellosis with IV ceftriaxone therapy in combination with oral therapy.
Topics: Adult; Humans; Child; Ceftriaxone; Administration, Oral; Brucella; Brucellosis; Fatigue
PubMed: 35930502
DOI: 10.1080/00207454.2022.2100776 -
Journal of Translational Medicine Oct 2023Animal models are widely used to study pathological processes and drug (side) effects in a controlled environment. There is a wide variety of methods available for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Animal models are widely used to study pathological processes and drug (side) effects in a controlled environment. There is a wide variety of methods available for establishing animal models depending on the research question. Commonly used methods in tumor research include xenografting cells (established/commercially available or primary patient-derived) or whole tumor pieces either orthotopically or heterotopically and the more recent genetically engineered models-each type with their own advantages and disadvantages. The current systematic review aimed to investigate the meningioma model types used, perform a meta-analysis on tumor take rate (TTR), and perform critical appraisal of the included studies. The study also aimed to assess reproducibility, reliability, means of validation and verification of models, alongside pros and cons and uses of the model types.
METHODS
We searched Medline, Embase, and Web of Science for all in vivo meningioma models. The primary outcome was tumor take rate. Meta-analysis was performed on tumor take rate followed by subgroup analyses on the number of cells and duration of incubation. The validity of the tumor models was assessed qualitatively. We performed critical appraisal of the methodological quality and quality of reporting for all included studies.
RESULTS
We included 114 unique records (78 using established cell line models (ECLM), 21 using primary patient-derived tumor models (PTM), 10 using genetically engineered models (GEM), and 11 using uncategorized models). TTRs for ECLM were 94% (95% CI 92-96) for orthotopic and 95% (93-96) for heterotopic. PTM showed lower TTRs [orthotopic 53% (33-72) and heterotopic 82% (73-89)] and finally GEM revealed a TTR of 34% (26-43).
CONCLUSION
This systematic review shows high consistent TTRs in established cell line models and varying TTRs in primary patient-derived models and genetically engineered models. However, we identified several issues regarding the quality of reporting and the methodological approach that reduce the validity, transparency, and reproducibility of studies and suggest a high risk of publication bias. Finally, each tumor model type has specific roles in research based on their advantages (and disadvantages).
SYSTEMATIC REVIEW REGISTRATION
PROSPERO-ID CRD42022308833.
Topics: Animals; Humans; Meningeal Neoplasms; Meningioma; Reproducibility of Results; Disease Models, Animal
PubMed: 37898750
DOI: 10.1186/s12967-023-04620-7 -
European Journal of Pediatrics Jan 2024The optimal duration of antibiotic treatment for the most common bacterial meningitis etiologies in the pediatric population, namely Streptococcus pneumoniae,... (Meta-Analysis)
Meta-Analysis Review
The optimal duration of antibiotic treatment for the most common bacterial meningitis etiologies in the pediatric population, namely Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, is not well-established in the literature. Therefore, we aimed to perform an updated meta-analysis comparing shorter versus longer antibiotic treatment in children with meningitis. PubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials (RCTs) that compared shorter (up to 7 days) versus longer (10 days or double the days of the equivalent short course) duration of antibiotic treatment in children with meningitis and reported the outcomes of treatment failure, death, neurologic sequelae, non-neurologic complications, hearing impairment, nosocomial infection, and relapse. Heterogeneity was examined with I statistics. RevMan 5.4.1 was used for statistical analysis and RoB-2 (Cochrane) for risk of bias assessment. Of 684 search results, 6 RCTs were included, with a cohort of 1333 children ages 3 weeks to 15.5 years, of whom 49.51% underwent a short antibiotic course. All RCTs included monotherapy with ceftriaxone, except one, which added vancomycin as well. No differences were found comparing the short and long duration of therapy concerning treatment failure, relapse, mortality, and neurologic complications at discharge and at follow-up. Conclusion: Because no statistically significant differences were found between groups for the analyzed outcomes, the results of this meta-analysis support shorter therapy. However, generalizing these results to complicated meningitis and infections caused by other pathogens should be made with caution. (PROSPERO identifier: CRD42022369843). What is Known: • Current recommendations on the duration of antibiotic therapy for bacterial meningitis are mostly based on clinical practice. • Defining an optimal duration of antibiotic therapy is essential for antimicrobial stewardship achievement, improving patient outcomes, and minimizing adverse effects. What is New: • There are no differences between shorter versus longer antibiotic treatment duration in regard to treatment failure, relapse, mortality, neurologic complications, and hearing impairment at discharge and at follow-up.
Topics: Child; Humans; Anti-Bacterial Agents; Meningitis, Bacterial; Ceftriaxone; Hearing Loss; Recurrence
PubMed: 37870611
DOI: 10.1007/s00431-023-05275-8 -
Neurosurgical Review Jul 2023Olfactory groove meningiomas (OGM) are a skull base neoplasm that represents between 8 and 13% of all intracranial meningiomas. Approach selection focuses on achieving... (Review)
Review
Olfactory groove meningiomas (OGM) are a skull base neoplasm that represents between 8 and 13% of all intracranial meningiomas. Approach selection focuses on achieving frontal lobe decompression, gross total resection and vision preservation. Recently, there has been a focus on olfaction and considering its preservation as a quality-of-life outcome measure. An electronic search of the databases Medline, Scopus, Embase, Web of Science and Cochrane library databases was performed and data extracted according 2020 Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) statement. Six articles were selected for inclusion mainly based due to reporting quantitative outcomes for olfaction assessed by a smell identification test (e.g. sniffin' sticks). Objective olfaction preservation can be achieved with a variety of surgical approaches. More research which includes objective assessment of olfactory function and ideally as well QoL outcome measures is needed to further optimize the treatment pathways in OGM patients.
Topics: Humans; Meningioma; Smell; Meningeal Neoplasms; Quality of Life; Olfaction Disorders
PubMed: 37500988
DOI: 10.1007/s10143-023-02096-z