Development and Validation of a Predictive Model for Postoperative Intracranial Infections in Neurosurgery with Risk Factor Analysis.

BACKGROUND: Currently, the diagnosis of postneurosurgical intracranial infection is mainly dependent on cerebrospinal fluid (CSF) bacterial culture, which has the disadvantages of being time-consuming, having a low detection rate, and being easily affected by other factors. These disadvantages bring some difficulties to early diagnosis. Therefore, it is very important to construct a nomogram model to predict the risk of infection and provide a basis for early diagnosis and treatment. METHODS: This retrospective study analyzed postneurosurgical patient data from the Fourth Affiliated Hospital of Harbin Medical University between January 2019 and September 2023. The patients were randomly assigned in an 8:2 ratio into the training cohort and the internal validation cohort. In the training cohort, initial screening of relevant indices was conducted via univariate analysis. Subsequently, the least absolute shrinkage and selection operator logistic regression identified significant potential risk factors for inclusion in the nomogram model. The model's discriminative ability was assessed using the area under the receiver operating characteristic curve, and its calibration was evaluated through calibration plots. The clinical utility of the model was determined using decision curve analysis and further validated by the internal validation cohort. RESULTS: Multivariate logistic regression analysis of the training cohort identified 7 independent risk factors for postoperative intracranial infection: duration of postoperative external drainage (odds ratio [OR] 1.19, P = 0.005), continued fever (OR 2.11, P = 0.036), CSF turbidity (OR 2.73, P = 0.014), CSF pressure (OR 1.01, P = 0.018), CSF total protein level (OR 1.26, P = 0.026), CSF glucose concentration (OR 0.74, P = 0.029), and postoperative serum albumin level (OR 0.84, P < 0.001). Using these variables to construct the final model. The area under the receiver operating characteristic curve value of the model was 0.868 in the training cohort and 0.900 in the internal validation cohort. Calibration and the decision curve analysis indicated high accuracy and clinical benefit of the nomogram, findings that were corroborated in the validation cohort. CONCLUSIONS: This study successfully developed a novel nomogram for predicting postoperative intracranial infection, demonstrating excellent predictive performance. It offers a pragmatic tool for the early diagnosis of intracranial infection.

Clinical spectrum, phenotypic and molecular characterization, and antifungal susceptibility of an emerging human pathogen, Acrophialophora, from India.

Acrophialophora is implicated in superficial and invasive infections, especially in immunosuppressed individuals. The present study was undertaken to provide clinical, microbiological, phylogenetic, and antifungal susceptibility testing (AFST) profile of Acrophialophora isolated from India. All the isolates identified as Acrophialophora species at the National Culture Collection for Pathogenic Fungi, Chandigarh, India were revived. Phenotypic and molecular characterization was performed, followed by temperature studies, scanning electron microscopy (SEM), and AFST. We also performed systematic review of all the cases of Acrophialophora species reported till date. A total of nine isolates identified as Acrophialophora species were identified by molecular method as A. fusispora (n = 8) and A. levis (n = 1), from brain abscess (n = 4), respiratory tract (n = 3), and corneal scraping (n = 2). All patients but two had predisposing factors/co-morbidities. Acrophialophora was identified as mere colonizer in one. Temperature studies and SEM divulged variation between both species. Sequencing of the internal transcribed spacer ribosomal DNA and beta-tubulin loci could distinguish species, while the LSU ribosomal DNA locus could not. AFST showed the lowest minimum inhibitory concentrations (MICs) for triazoles and the highest for echinocandins. Systematic literature review revealed 16 cases (11 studies), with ocular infections, pulmonary and central nervous system infections, and A. fusispora was common species. All the patients except three responded well. High MICs were noted for fluconazole, micafungin, and caspofungin. This is the first study delineating clinical, phenotypic, and genotypic characteristics of Acrophialophora species from India. The study highlights microscopic differences between both species and emphasizes the role of molecular methods in precise identification. Triazoles appear to be the most effective antifungals for managing patients.

We describe clinical, phenotypic, and genotypic characteristics of Acrophialophora species. This species causes mild infection to fatal infection in immunosuppressed individuals. Triazoles are effective in treating such infections.

Contribution of CNS and extra-CNS infections to neurodegeneration: a narrative review.

Central nervous system infections have been suggested as a possible cause for neurodegenerative diseases, particularly sporadic cases. They trigger neuroinflammation which is considered integrally involved in neurodegenerative processes. In this review, we will look at data linking a variety of viral, bacterial, fungal, and protozoan infections to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis and unspecified dementia. This narrative review aims to bring together a broad range of data currently supporting the involvement of central nervous system infections in the development of neurodegenerative diseases. The idea that no single pathogen or pathogen group is responsible for neurodegenerative diseases will be discussed. Instead, we suggest that a wide range of susceptibility factors may make individuals differentially vulnerable to different infectious pathogens and subsequent pathologies.

Varicella zoster virus-induced autophagy in human neuronal and hematopoietic cells exerts antiviral activity.

Autophagy is a degradational pathway with pivotal roles in cellular homeostasis and survival, including protection of neurons in the central nervous system (CNS). The significance of autophagy as antiviral defense mechanism is recognized and some viruses hijack and modulate this process to their advantage in certain cell types. Here, we present data demonstrating that the human neurotropic herpesvirus varicella zoster virus (VZV) induces autophagy in human SH-SY5Y neuronal cells, in which the pathway exerts antiviral activity. Productively VZV-infected SH-SY5Y cells showed increased LC3-I-LC3-II conversion as well as co-localization of the viral glycoprotein E and the autophagy receptor p62. The activation of autophagy was dependent on a functional viral genome. Interestingly, inducers of autophagy reduced viral transcription, whereas inhibition of autophagy increased viral transcript expression. Finally, the genotype of patients with severe ocular and brain VZV infection were analyzed to identify potential autophagy-associated inborn errors of immunity. Two patients expressing genetic variants in the autophagy genes ULK1 and MAP1LC3B2, respectively, were identified. Notably, cells of both patients showed reduced autophagy, alongside enhanced viral replication and death of VZV-infected cells. In conclusion, these results demonstrate a neuro-protective role for autophagy in the context of VZV infection and suggest that failure to mount an autophagy response is a potential predisposing factor for development of severe VZV disease.

TAK-3 Inhibits Lipopolysaccharide-Induced Neuroinflammation in Traumatic Brain Injury Rats Through the TLR-4/NF-κB Pathway.

Purpose: The activation of the inflammatory response is regarded as a pivotal factor in the pathogenesis of TBI. Central nervous system infection often leads to the exacerbation of neuroinflammation following TBI, primarily caused by Gram-negative bacteria. This study aims to elucidate the effects of the novel anti-inflammatory drug TAK-3 on LPS-induced neuroinflammation in TBI rats. Methods: In conjunction with the rat controlled cortical impact model, we administered local injections of Lipopolysaccharide to the impact site. Subsequently, interventions were implemented through intraperitoneal injections of TAK-3 and NF-κB activitor2 to modulate the TLR4/NF-κB axis The impact of LPS on neurological function was assessed using mNSS, open field test, and brain water content measurement. Inflammatory markers, including TNF-α, IL-1ß, IL-6 and IL-10 were assessed to evaluate the condition of neuritis by Elisa. The activation of the TLR-4/NF-κB signaling pathway was detected by immunofluorescence staining and Western blot to assess the anti-inflammatory effects of TAK-3. Results: The administration of LPS exacerbated neurological damage in rats with TBI, as evidenced by a reduction in motor activity and an increase in anxiety-like behavior. Furthermore, LPS induced disruption of the blood-brain barrier integrity and facilitated the development of brain edema. The activation of microglia and astrocytes by LPS at the cellular and molecular levels has been demonstrated to induce a significant upregulation of neuroinflammatory factors. The injection of TAK-3 attenuated the neuroinflammatory response induced by LPS. Conclusion: The present study highlights the exacerbating effects of LPS on neuroinflammation in TBI through activation of the TLR-4/NF-κB signaling pathway. TAK-3 can modulate the activity of this signaling axis, thereby attenuating neuroinflammation and ultimately reducing brain tissue damage.

EBV-associated CNS infection in an immunocompetent adult: A case report and literature review.

EBV infections rarely cause CNS involvement. For young adult patients with suspected CNS infection, bacterial and other common viral infections should be excluded first and treated empirically until proven otherwise. Challenges in diagnosing EBV-associated CNS infection, emphasizing the role of CSF PCR in confirming the diagnosis.

A Study of the Etiology, Clinical Profile, and Diagnosis of Various Types of Central Nervous System Infections in a Tertiary Care Center.

Introduction Infections affecting the central nervous system (CNS) can stem from various sources, including bacteria, viruses, and fungi, manifesting as conditions like meningitis, encephalitis, meningoencephalitis, and brain abscesses. Despite significant advancements in diagnosis and treatment, these infections continue to pose substantial risks to life. Several factors contribute to the causes of CNS infections. Demographic and geographic elements, the health status of individuals, their immune system's strength, the availability of diagnostic tools, and local prevention initiatives, all play pivotal roles. Consequently, the necessity of comprehensive local epidemiological data becomes undeniable as it guides the need for further studies and research. Understanding these factors is crucial for enhancing preventive measures and optimizing treatment strategies in tackling CNS infections. Aims and objectives This research aims to study the etiology and clinical features of different CNS infections among hospitalized patients and to diagnose cases of CNS infections based on laboratory and radiological investigations. Material and methods One hundred adults, seeking treatment for neurological impairments at a specialized tertiary care center in Gujarat, India, volunteered for this cross-sectional observational research. The study investigated the etiology, clinical profiles, and diagnoses of different CNS infections. It delved into the prevalence of these infections across age and sex categories while also observing mortality rates. Results In our research, we observed that bacterial causes were the most prevalent among CNS infections. Tubercular meningitis accounted for 36%, tuberculoma 14%, and pyogenic bacterial infections 23%. Following this, fungal infections emerged as the second most frequent, with mucormycosis at 9% and cryptococcus at 1%. Other less common CNS infections included viral encephalitis (4%), neurocysticercosis (3%), and brain abscess (1%). Middle-aged individuals between 41 and 60 years were most commonly affected (43%), followed by those aged 21-40 years (31%). Males accounted for a higher percentage of cases at 58%. Clinical symptoms revealed fever as the predominant feature (80%), with headaches following closely at 67%. Acute presentations were prevalent, representing 83% of cases, while neck stiffness was noted in 62% of patients. Most patients exhibited normal hemoglobin levels (96%) and a majority had a normal total leukocyte count (79%). Notably, 31% of the studied patients were identified as People Living With HIV (PLHIV). Out of 100 patients, 79 survived with appropriate treatment, resulting in a mortality of 21%. Conclusion The study identified various CNS infections, including bacterial (acute pyogenic meningitis, tubercular meningitis, tuberculoma, brain abscesses, and neurosyphilis), viral (viral meningitis and encephalitis), fungal (cryptococcal meningitis and CNS mucormycosis), and parasitic infections (neurocysticercosis and CNS toxoplasmosis). Tuberculous meningitis emerged as the most prevalent, followed by pyogenic meningitis. Clinical symptoms predominantly featured fever, headache, and altered sensorium, with less common occurrences of seizures, vomiting, weakness, and speech disturbances. Elevated CSF proteins and total leukocyte count were common findings in CSF analysis while consistent radiological observations included hypodensities in brain tissue and leptomeningeal enhancement.

Computed tomography and magnetic resonance imaging findings in central nervous system listeriosis.

PURPOSE: To describe the imaging findings and determine the incidence of a characteristic worm-like pattern along the white matter tracts in neurolisteriosis on CT/MRI. METHODS: An IRB-approved retrospective study in 21 consecutive neurolisteriosis cases during January 2002-July 2020. At least one of the following is required: (1) Positive Listeria monocytogenes (LM) in blood with clinical signs of meningeal irritation and/or abnormal CSF profile, (2) positive LM in blood with signs of encephalitis, (3) positive LM in CSF, (4) positive LM from brain biopsy/aspiration. Six cases were excluded due to the lack of contrast-enhanced images, leaving a total of 15 cases for analysis (mean age 53.5 years ± 18.8 SD). The imaging studies were independently reviewed by two blinded readers. Demographic data, imaging findings, and incidence of the worm-like pattern were reported. The Cohen's kappa was used to calculate interrater reproducibility. RESULTS: Of the 12 patients with relevant imaging findings, nine cases (75%) had parenchymal lesions (eight cases in supratentorial compartment and one case in infratentorial compartment), four cases (33.3%) had leptomeningeal enhancement and two cases (16.7%) had hydrocephalus. Brain abscesses were found in eight cases and nodules evocative of abscess in one case. Restricted diffusion in the central area and hemosiderin deposition were observed in all cases. The involvement of white matter tract in a worm-like pattern was demonstrated in eight of nine patients with parenchymal lesions (88.9%). CONCLUSION: Abnormal findings in brain CT/MRI images are common in neurolisteriosis. The incidence of worm-like spread along the white matter tracts is high and may help diagnose suspicious patients.

Microbiomes detected by cerebrospinal fluid metagenomic next-generation sequencing among patients with and without HIV with suspected central nervous system infection.

BACKGROUND: Opportunistic infections in the central nervous system (CNS) can be a serious threat to people living with HIV. Early aetiological diagnosis and targeted treatment are crucial but difficult. Metagenomic next-generation sequencing (mNGS) has significant advantages over traditional detection methods. However, differences in the cerebrospinal fluid (CSF) microbiome profiles of patients living with and without HIV with suspected CNS infections using mNGS and conventional testing methods have not yet been adequately evaluated. METHODS: We conducted a retrospective cohort study in the first hospital of Changsha between January 2019 and June 2022 to investigate the microbiomes detected using mNGS of the CSF of patients living with and without HIV with suspected CNS infections. The pathogens causing CNS infections were concurrently identified using both mNGS and traditional detection methods. The spectrum of pathogens identified was compared between the two groups. RESULTS: Overall, 173 patients (140 with and 33 without HIV) with suspected CNS infection were enrolled in our study. In total, 106 (75.7%) patients with and 16 (48.5%) patients without HIV tested positive with mNGS (p = 0.002). Among the enrolled patients, 71 (50.7%) with HIV and five (15.2%) without HIV tested positive for two or more pathogens (p < 0.001). Patients with HIV had significantly higher proportions of fungus (20.7% vs. 3.0%, p = 0.016) and DNA virus (59.3% vs. 21.2%, p < 0.001) than those without HIV. Epstein-Barr virus (33.6%) was the most commonly identified potential pathogen in the CSF of patients living with HIV using mNGS, followed by cytomegalovirus (20.7%) and torque teno virus (13.8%). The top three causative pathogens identified in patients without HIV were Streptococcus (18.2%), Epstein-Barr virus (12.1%), and Mycobacterium tuberculosis (9.1%). In total, 113 patients living with HIV were diagnosed as having CNS infections. The rate of pathogen detection in people living with HIV with a CNS infection was significantly higher with mNGS than with conventional methods (93.8% vs. 15.0%, p < 0.001). CONCLUSION: CSF microbiome profiles differ between patients living with and without HIV with suspected CNS infection. mNGS is a powerful tool for the diagnosis of CNS infection among people living with HIV, especially in those with mixed infections.

Diagnostic accuracy of inflammatory markers in adults with suspected central nervous system infections.

OBJECTIVES: We aimed to determine diagnostic accuracy of inflammatory markers in plasma and cerebrospinal fluid (CSF) for the diagnosis of central nervous system (CNS) infections and specifically bacterial meningitis. METHODS: We analyzed 12 cytokines, chemokines, and acute phase reactants in CSF and plasma of 738 patients with suspected neurological infection included in a multicenter prospective cohort. We determined diagnostic accuracy for predicting any CNS infection and bacterial meningitis. RESULTS: We included 738 episodes between 2017 and 2022, split into a derivation (n = 450) and validation cohort (n = 288). Of these patients, 224 (30%) were diagnosed with CNS infection, of which 81 (11%) with bacterial meningitis, 107 (14%) with viral meningitis or encephalitis, and 35 patients (5%) with another CNS infection. Diagnostic accuracy of CRP, IL-6, and Il-1ß in CSF was high, especially for diagnosing bacterial meningitis. Combining these biomarkers in a multivariable model increased accuracy and provided excellent discrimination between bacterial meningitis and all other disorders (AUC = 0.99), outperforming all individual biomarkers as well as CSF leukocytes (AUC = 0.97). When applied to the population of patients with a CSF leukocyte count of 5-1000 cells/mm3, accuracy of the model also provided a high diagnostic accuracy (AUC model = 0.97 vs. AUC CSF leukocytes = 0.80) with 100% sensitivity and 92% specificity. These results remained robust in a temporal validation cohort. CONCLUSIONS: Inflammatory biomarkers in CSF are able to differentiate CNS infections and especially bacterial meningitis from other disorders. When these biomarkers are combined, their diagnostic accuracy exceeds that of CSF leukocytes alone and as such these markers have added value to current clinical practice.

Clinical and Radiological Characterization of Central Nervous System Involvement in Nocardiosis: A 20-Year Experience.

Background This study aimed to present the clinical and radiological characteristics and the outcomes of patients with Nocardia infection of the central nervous system (CNS). Methodology We conducted a retrospective review of patients aged 18 and older admitted between August 1998 and November 2018 with culture-proven nocardiosis and CNS involvement. Results Out of 110 patients with nocardiosis, 14 (12.7%) patients had CNS involvement. The median age was 54.5 (27, 86) years, and 12 (85.7%) patients were male. Overall, 12 (85.7%) patients were immunosuppressed on high doses of glucocorticoids; seven (50%) patients were solid organ transplant recipients. Only eight (57.1%) patients had neurological symptoms at presentation, and the rest were diagnosed with CNS involvement after imaging surveillance. Three distinct radiologic patterns were identified, namely, single or multiple abscesses, focal cerebritis, and small, septic embolic infarcts. All isolates of Nocardia were susceptible to trimethoprim/sulfamethoxazole and amikacin, with susceptibility to linezolid and carbapenems being 90.9% and 79.5%, respectively. Despite receiving antibiotic therapy, six (42.8%) patients died, most of them within weeks of initial admission. All surviving patients underwent prolonged antimicrobial therapy until the resolution of MRI abnormalities. All solid organ transplant recipients recovered. Conclusions Nocardia CNS infection was a rare condition, even among a large, immunosuppressed patient population. CNS imaging surveillance is paramount for immunosuppressed patients with nocardiosis, as CNS involvement influences the choice and duration of therapy. Nocardia antibiotic susceptibility varied widely between strains and the empiric therapy should consist of multiple classes of antimicrobials with CNS penetration. Mortality was high, but all solid organ transplant recipients recovered.

Clinical presentation, management, and outcome of suspected central nervous system infections in Indonesia: a prospective cohort study.

BACKGROUND: Little is known about the etiology, clinical presentation, management, and outcome of central nervous system (CNS) infections in Indonesia, a country with a high burden of infectious diseases and a rising prevalence of HIV. METHODS: We included adult patients with suspected CNS infections at two referral hospitals in a prospective cohort between April 2019 and December 2021. Clinical, laboratory, and radiological assessments were standardized. We recorded initial and final diagnoses, treatments, and outcomes during 6 months of follow-up. RESULTS: Of 1051 patients screened, 793 were diagnosed with a CNS infection. Patients (median age 33 years, 62% male, 38% HIV-infected) presented a median of 14 days (IQR 7-30) after symptom onset, often with altered consciousness (63%), motor deficits (73%), and seizures (21%). Among HIV-uninfected patients, CNS tuberculosis (TB) was most common (60%), while viral (8%) and bacterial (4%) disease were uncommon. Among HIV-infected patients, cerebral toxoplasmosis (41%) was most common, followed by CNS TB (19%), neurosyphilis (15%), and cryptococcal meningitis (10%). A microbiologically confirmed diagnosis was achieved in 25% of cases, and initial diagnoses were revised in 46% of cases. In-hospital mortality was 30%, and at six months, 45% of patients had died, and 12% suffered from severe disability. Six-month mortality was associated with older age, HIV, and severe clinical, radiological and CSF markers at presentation. CONCLUSION: CNS infections in Indonesia are characterized by late presentation, severe disease, frequent HIV coinfection, low microbiological confirmation and high mortality. These findings highlight the need for earlier disease recognition, faster and more accurate diagnosis, and optimized treatment, coupled with wider efforts to improve the uptake of HIV services.

Pro-inflammatory cerebrospinal fluid profile of neonates with intraventricular hemorrhage: clinical relevance and contrast with CNS infection.

BACKGROUND: Interpretation of cerebrospinal fluid (CSF) studies can be challenging in preterm infants. We hypothesized that intraventricular hemorrhage (IVH), post-hemorrhagic hydrocephalus (PHH), and infection (meningitis) promote pro-inflammatory CSF conditions reflected in CSF parameters. METHODS: Biochemical and cytological profiles of lumbar CSF and peripheral blood samples were analyzed for 81 control, 29 IVH grade 1/2 (IVH1/2), 13 IVH grade 3/4 (IVH3/4), 15 PHH, 20 culture-confirmed bacterial meningitis (BM), and 27 viral meningitis (VM) infants at 36.5 ± 4 weeks estimated gestational age. RESULTS: PHH infants had higher (p < 0.02) CSF total cell and red blood cell (RBC) counts compared to control, IVH1/2, BM, and VM infants. No differences in white blood cell (WBC) count were found between IVH3/4, PHH, BM, and VM infants. CSF neutrophil counts increased (p ≤ 0.03) for all groups compared to controls except IVH1/2. CSF protein levels were higher (p ≤ 0.02) and CSF glucose levels were lower (p ≤ 0.003) for PHH infants compared to all other groups. In peripheral blood, PHH infants had higher (p ≤ 0.001) WBC counts and lower (p ≤ 0.03) hemoglobin and hematocrit than all groups except for IVH3/4. CONCLUSIONS: Similarities in CSF parameters may reflect common pathological processes in the inflammatory response and show the complexity associated with interpreting CSF profiles, especially in PHH and meningitis/ventriculitis.

Diagnostic accuracy of clinical and laboratory characteristics in suspected non-surgical nosocomial central nervous system infections.

BACKGROUND: The diagnosis of meningitis in non-surgical hospitalized patients is often difficult and diagnostic accuracy of clinical, laboratory, and radiological characteristics is unknown. AIM: To assess diagnostic accuracy for individual clinical characteristics of patients suspected of non-surgical nosocomial central nervous system (CNS) infections. METHODS: In a prospective multi-centre cohort study in the Netherlands with adults suspected of CNS infections, consecutive patients who underwent a lumbar puncture for the suspicion of a non-surgical nosocomial CNS infection were included. All episodes were categorized into five final clinical diagnosis categories, as reference standard: CNS infection, CNS inflammatory disease, systemic infection, other neurological disease, or non-systemic, non-neurological disease. FINDINGS: Between 2012 and 2022, 114 out of 1275 (9%) patients included in the cohort had suspected non-surgical nosocomial CNS infection: 16 (14%) had a confirmed diagnosis, including four (25%) with bacterial meningitis, nine (56%) with viral CNS infections, two (13%) fungal meningitis, and one (6%) parasitic meningitis. Diagnostic accuracy of individual clinical characteristics was generally low. Elevated CSF leucocyte count had the highest sensitivity (81%; 95% confidence interval (CI): 54-96) and negative predictive value (NPV) (96%; 95% CI: 90-99). When combining the presence of abnormalities in neurological or CSF examination, sensitivity for diagnosing a CNS infection was 100% (95% CI: 79-100) and NPV 100% (95% CI: 78-100). CSF examination changed clinical management in 47% of patients. CONCLUSION: Diagnostic accuracy for individual clinical characteristics was low, with elevated CSF leucocyte count having the highest sensitivity and NPV.

Techniques to Reduce the Rate of Infection in Surgeries for Cerebrospinal Fluid Shunting in Adults.

OBJECTIVE: Cerebrospinal fluid shunt placement is associated with high rates of infection. Multiple standardized protocols, particularly in pediatric populations, have been proposed to mitigate this infection rate. We sought to determine the effectiveness of a standardized shunt infection protocol in a large adult population. METHODS: A retrospective cohort study of adults presenting for primary cerebrospinal fluid shunt placement from 2012 to 2022. The primary outcome of interest was shunt infection. The primary exposure of interest was implementation of the shunt protocol (began October 2015). Secondary exposures of interest included use and type of perioperative antibiotics and total operating room time. RESULTS: In total, 820 patients were included, 140 before protocol implementation and 680 after protocol implementation. The overall number of infections over the study period was 15 (1.8% infection rate), with 8 infections preprotocol (5.7%) and 7 infections during the protocol period (1.0%). The infection protocol was associated with a decreased infection rate (odds rato [OR] 0.18, 95% confidence interval [CI] 0.05-0.58, P = 0.002). Total operating room time (OR 1.38 per 30-minute increase, 95% CI 1.05-1.81, P = 0.021) was associated with increased infection rate. Patients who received antibiotics with primarily gram-positive coverage (cefazolin or equivalent) did not have significantly different odds of shunt infection as patients who received broad-spectrum coverage (OR 2.10, 95% CI 0.56-7.88, P = 0.274). CONCLUSIONS: The implementation of an evidence-based perioperative shunt infection protocol is an effective method to decrease shunt infections. Broad-spectrum perioperative antibiotics may not have greater efficacy than gram-positive only coverage, but more research is required.

Application of cell-free plasma next-generation sequencing technology in the diagnosis and management of pediatric meningitis.

This retrospective study evaluates the clinical utility of CFPNGS in the diagnosis and management of pediatric meningitis. CFPNGS identified a causative pathogen in 36% of 28 subjects, compared to 50% for diverse conventional testing (57% combined). CFPNGS may be considered as an adjunct to standard testing.

Nomogram for Predicting Central Nervous System Infection Following Traumatic Brain Injury in the Elderly.

OBJECTIVE: This study aims to identify risk factors for central nervous system (CNS) infection in elderly patients hospitalized with traumatic brain injury (TBI) and to develop a reliable predictive tool for assessing the likelihood of CNS infection in this population. METHOD: We conducted a retrospective study on 742 elderly TBI patients treated at Tangdu Hospital, China. Clinical data was randomly split into training and validation sets (7:3 ratio). By conducting univariate and multivariate logistic regression analysis in the training set, we identified a list of variables to develop a nomogram for predicting the risk of CNS infection. We evaluated the performance of the predictive model in both cohorts respectively, using receiver operating characteristics curves, calibration curves, and decision curve analysis. RESULTS: Results of the logistic analysis in the training set indicated that surgical intervention (P = 0.007), red blood cell count (P = 0.019), C-reactive protein concentration (P < 0.001), and cerebrospinal fluid leakage (P < 0.001) significantly predicted the occurrence of CNS infection in elderly TBI patients. The model constructed based on these variables had high predictive capability (area under the curve-training = 0.832; area under the curve-validation = 0.824) as well as clinical utility. CONCLUSIONS: A nomogram constructed based on several key predictors reasonably predicts the risk of CNS infection in elderly TBI patients upon hospital admission. The model of the nanogram may contribute to timely interventions and improve health outcomes among affected individuals.

Molecular Mechanisms Associated with Neurodegeneration of Neurotropic Viral Infection.

Viral infections of the central nervous system (CNS) cause variable outcomes from acute to severe neurological sequelae with increased morbidity and mortality. Viral neuroinvasion directly or indirectly induces encephalitis via dysregulation of the immune response and contributes to the alteration of neuronal function and the degeneration of neuronal cells. This review provides an overview of the cellular and molecular mechanisms of virus-induced neurodegeneration. Neurotropic viral infections influence many aspects of neuronal dysfunction, including promoting chronic inflammation, inducing cellular oxidative stress, impairing mitophagy, encountering mitochondrial dynamics, enhancing metabolic rewiring, altering neurotransmitter systems, and inducing misfolded and aggregated pathological proteins associated with neurodegenerative diseases. These pathogenetic mechanisms create a multidimensional injury of the brain that leads to specific neuronal and brain dysfunction. The understanding of the molecular mechanisms underlying the neurophathogenesis associated with neurodegeneration of viral infection may emphasize the strategies for prevention, protection, and treatment of virus infection of the CNS.

The emerging mechanism behind viral infections and extracellular vesicles hypotheses leading to neuroinflammation and Alzheimer's disease pathology.

Despite decades of repeated and intense research, the etiology of sudden Alzheimer's disease (AD) symptoms is still unclear. AD progressive pathology mainly involves neuron damage, depositions of amyloid-beta (Aß), and hyperphosphorylated tau protein. All these defects are manifested by exaggerated cytokine storm and neuroinflammation leading to irreversible brain damage in the long term. Despite the numerous risks and drawbacks associated with AD, it is believed that there is a hidden unknown causative and predisposing factors for AD. Extracellular vesicles (EVs) are small vesicles released by cells as a type of intercellular communication. Several pieces of evidence support the inclusion of viral components within EVs facilitating their penetration into the blood-brain barrier leading to neuroinflammation. In light of the SARS-CoV-19 pandemic and its related neurological complications, it is mandatory to highlight the possibility and viability of viral infections such as varicella-zoster virus (VZV) and herpes simplex virus (HSV) on the onset of AD. Herein, the author is investigating the potential role of VZV and HSV along with highlighting the suggested route of pathogenesis entry resulting in AD manifestations. Additionally, this review aims to summarize the role of EVs in mediating the central nervous system viral infections leading to AD.

The Promise of Molecular Imaging: Focus on Central Nervous System Infections.

Central nervous system (CNS) infections can lead to high mortality and severe morbidity. Diagnosis, monitoring, and assessing response to therapy of CNS infections is particularly challenging with traditional tools, such as microbiology, due to the dangers associated with invasive CNS procedures (ie, biopsy or surgical resection) to obtain tissues. Molecular imaging techniques like positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging have long been used to complement anatomic imaging such as computed tomography (CT) and magnetic resonance imaging (MRI), for in vivo evaluation of disease pathophysiology, progression, and treatment response. In this review, we detail the use of molecular imaging to delineate host-pathogen interactions, elucidate antimicrobial pharmacokinetics, and monitor treatment response. We also discuss the utility of pathogen-specific radiotracers to accurately diagnose CNS infections and strategies to develop radiotracers that would cross the blood-brain barrier.