Project description:BackgroundCerebrospinal fluid shunt infection can be recalcitrant. Recurrence is common despite appropriate therapy for the pathogens identified by culture. Improved diagnostic and therapeutic approaches are required, and culture-independent molecular approaches to cerebrospinal fluid shunt infections have not been described.ObjectivesTo identify the bacteria and fungi present in cerebrospinal fluid from children with cerebrospinal fluid shunt infection using a high-throughput sequencing approach, and to compare those results to those from negative controls and conventional culture.MethodsThis descriptive study included eight children ≤18 years old undergoing treatment for culture-identified cerebrospinal fluid shunt infection. After routine aerobic culture of each cerebrospinal fluid sample, deoxyribonucleic acid (DNA) extraction was followed by amplification of the bacterial 16S rRNA gene and the fungal ITS DNA region tag-encoded FLX-Titanium amplicon pyrosequencing and microbial phylogenetic analysis.ResultsThe microbiota analyses for the initial cerebrospinal fluid samples from all eight infections identified a variety of bacteria and fungi, many of which did not grow in conventional culture. Detection by conventional culture did not predict the relative abundance of an organism by pyrosequencing, but in all cases, at least one bacterial taxon was detected by both conventional culture and pyrosequencing. Individual bacterial species fluctuated in relative abundance but remained above the limits of detection during infection treatment.ConclusionsNumerous bacterial and fungal organisms were detected in these cerebrospinal fluid shunt infections, even during and after treatment, indicating diverse and recalcitrant shunt microbiota. In evaluating cerebrospinal fluid shunt infection, fungal and anaerobic bacterial cultures should be considered in addition to aerobic bacterial cultures, and culture-independent approaches offer a promising alternative diagnostic approach. More effective treatment of cerebrospinal fluid shunt infections is needed to reduce unacceptably high rates of reinfection, and this work suggests that one effective strategy may be reduction of the diverse microbiota present in infection.
Project description:BackgroundCerebrospinal fluid (CSF) shunt infections in children represent an increasing problem in clinical practice. However, comprehensive clinical, laboratory and microbiologic data are scarce in pediatric age.MethodsWe conducted a 10-year retrospective study to (1) analyze clinical, laboratory and microbiologic parameters associated with infections in children; (2) analyze results according to the type of catheter (medicated or not), type of infection (first or relapses), type of hydrocephalus (acquired and congenital), presence or not of bacteriemia; (3) describe antibiotic susceptibilities and their evolution during the study period.ResultsEighty-seven children with shunt infection and 61 children with mechanical shunt malfunction were enrolled. Fever, vomit, leukocytosis and elevated C-reactive protein were more frequent in the infected group (P < 0.001), while neurologic symptoms developed more frequently in the noninfected group (10.3% vs. 27.87%; P = 0.006). Local signs of inflammation and abdomen distension were similarly reported in the 2 groups. Children with medicated shunts had lower cell count in the CSF (12/mm3) compared with those with nonmedicated shunts (380/mm3; P < 0.0001). Gram-negative bacteria were more common in the not-medicated catheters (90.91% vs. 50% of cultures; P = 0.04). Gram-negative bacteria were identified in 50.67% of CSF cultures, Gram-positive bacteria in 53.33% and fungi were observed in 5.33%. Sixteen children (18.4%) had also a positive blood culture. Enterococci isolation was associated with relapsed infections (37.50% vs. 15.25%; P = 0.05).ConclusionsOur study shows that the diagnosis and management of children with shunt infections are challenging. Prospective studies with a comprehensive approach focusing on patient, medical, microbiologic and surgical risk factors for first infection are urgently needed.
Project description:The object of this study was to determine whether cerebrospinal fluid (CSF) shunt revision(s) are associated with increased risk of CSF shunt infection, after adjusting for baseline factors that contribute to infection risk.This was a retrospective cohort study of 579 children aged 0-18 years who underwent initial CSF shunt placement between January 01, 1997 and October 12, 2006 at a tertiary care children's hospital. The outcome of interest was CSF shunt infection. Data for all subsequent CSF shunt revisions leading up to and including the initial CSF shunt infection, when applicable, were obtained. The likelihood of infection was determined using a Cox proportional hazard model accounting for patient characteristics and CSF shunt revisions, and is reported using hazard ratios (HR) with 95% confidence intervals (CI).There were 123 children who developed infection. Baseline factors independently associated with hazard of infection included age 0 to <6 months at CSF shunt placement (HR 2.4, 95% CI: 1.02-6.7) and myelomeningocele (HR 0.4, 95% CI: 0.2-0.8). Controlling for baseline factors, the risk of infection after shunt revision was significantly greater than at the time of initial placement (HR 3.0, 95% CI: 1.9-4.7), and this risk increased as numbers of revisions increased (?2 revisions HR 6.5, 95% CI: 3.6-11.4).Although younger age is associated with increased hazard of infection, subsequent CSF shunt revision significantly increases infection risk.
Project description:Molecular biomarkers for neurodegenerative diseases are critical for advancing diagnosis and therapy. Normal pressure hydrocephalus (NPH) is a neurological disorder characterized by progressive neurodegeneration, gait impairment, urinary incontinence and cognitive decline. In contrast to most other neurodegenerative disorders, NPH symptoms can be improved by the placement of a ventricular shunt that drains excess CSF. A major challenge in NPH management is the identification of patients who benefit from shunt surgery. Here, we perform genome-wide RNA sequencing of extracellular vesicles in CSF of 42 NPH patients, and we identify genes and pathways whose expression levels correlate with gait, urinary or cognitive symptom improvement after shunt surgery. We describe a machine learning algorithm trained on these gene expression profiles to predict shunt surgery response with high accuracy. The transcriptomic signatures we identified may have important implications for improving NPH diagnosis and treatment and for understanding disease aetiology.
Project description:BackgroundApproximately 30% of cerebrospinal fluid (CSF) shunt systems for hydrocephalus fail within the first year and 98% of all patients will have shunt failure in their lifetime. Obstruction remains the most common reason for shunt failure. Previous evidence suggests elevated pro-inflammatory cytokines in CSF are associated with worsening clinical outcomes in neuroinflammatory diseases. The aim of this study was to determine whether cytokines and matrix metalloproteinases (MMPs) contribute towards shunt failure in hydrocephalus.MethodsUsing multiplex ELISA, this study examined shunt failure through the CSF protein concentration profiles of select pro-inflammatory and anti-inflammatory cytokines, as well as select MMPs. Interdependencies such as the past number of previous revisions, length of time implanted, patient age, and obstruction or non-obstruction revision were examined. The pro-inflammatory cytokines were IL-1?, IL-2, IL-5, IL-6, IL-8, IL-12, IL-17, TNF-?, GM-CSF, IFN-?. The anti-inflammatory cytokines were IL-4 and IL-10, and the MMPs were MMP-2, MMP-3, MMP-7, MMP-9. Protein concentration is reported as pg/mL for each analyte.ResultsPatient CSF was obtained at the time of shunt revision operation; all pediatric (<?18), totaling n?=?38. IL-10, IL-6, IL-8 and MMP-7 demonstrated significantly increased concentrations in patient CSF for the non-obstructed subgroup. Etiological examination revealed IL-6 was increased in both obstructed and non-obstructed cases for PHH and congenital hydrocephalic patients, while IL-8 was higher only in PHH patients. In terms of number of past revisions, IL-10, IL-6, IL-8, MMP-7 and MMP-9 progressively increased from zero to two past revisions and then remained low for subsequent revisions. This presentation was notably absent in the obstruction subgroup. Shunts implanted for three months or less showed significantly increased concentrations of IL-6, IL-8, and MMP-7 in the obstruction subgroup. Lastly, only patients aged six months or less presented with significantly increased concentration of IL-8 and MMP-7.ConclusionNon-obstructive cases are reported here to accompany significantly higher CSF cytokine and MMP protein levels compared to obstructive cases for IL-10, IL-6, IL-8, MMP-7 and MMP-9. A closer examination of the definition of obstruction and the role neuroinflammation plays in creating shunt obstruction in hydrocephalic patients is suggested.
Project description:BackgroundProlonged external ventricular drainage (EVD) in patients with subarachnoid hemorrhage (SAH) leads to morbidity, whereas early removal can have untoward effects related to recurrent hydrocephalus. A metric to help determine the optimal time for EVD removal or ventriculoperitoneal shunt (VPS) placement would be beneficial in preventing the prolonged, unnecessary use of EVD. This study aimed to identify whether dynamics of cerebrospinal fluid (CSF) biometrics can temporally predict VPS dependency after SAH.MethodsThis was a retrospective analysis of a prospective, single-center, observational study of patients with aneurysmal SAH who required EVD placement for hydrocephalus. Patients were divided into VPS-dependent (VPS+) and non-VPS dependent groups. We measured the bicaudate index (BCI) on all available computed tomography scans and calculated the change over time (ΔBCI). We analyzed the relationship of ΔBCI with CSF output by using Pearson's correlation. A k-nearest neighbor model of the relationship between ΔBCI and CSF output was computed to classify VPS.ResultsFifty-eight patients met inclusion criteria. CSF output was significantly higher in the VPS+ group in the 7 days post EVD placement. There was a negative correlation between delta BCI and CSF output in the VPS+ group (negative delta BCI means ventricles become smaller) and a positive correlation in the VPS- group starting from days four to six after EVD placement (p < 0.05). A weighted k-nearest neighbor model for classification had a sensitivity of 0.75, a specificity of 0.70, and an area under the receiver operating characteristic curve of 0.80.ConclusionsThe correlation of ΔBCI and CSF output is a reliable intraindividual biometric for VPS dependency after SAH as early as days four to six after EVD placement. Our machine learning model leverages this relationship between ΔBCI and cumulative CSF output to predict VPS dependency. Early knowledge of VPS dependency could be studied to reduce EVD duration in many centers (intensive care unit length of stay).
Project description:BackgroundNearly 20% of patients with cerebrospinal fluid (CSF) shunt infection develop reinfection. It is unclear whether reinfections are caused by an organism previously present or are independent infection events.ObjectiveWe used bacterial culture and high throughput sequencing (HTS) of 16S ribosomal RNA (rRNA) genes to identify bacteria present in serial CSF samples obtained from children who failed CSF shunt infection treatment. We hypothesized that organisms that persist in CSF despite treatment would be detected upon reinfection.Design/methodsSerial CSF samples were obtained from 6 patients, 5 with 2 infections and 1 with 3 infections; the study was limited to those for which CSF samples were available from the end of infection and beginning of reinfection. Amplicons of the 16S rRNA gene V4 region were sequenced. Taxonomic assignments of V4 sequences were compared with bacterial species identified in culture.ResultsSeven infection dyads averaging 13.5 samples per infection were analyzed. A median of 8 taxa [interquartile range (IQR) 5-10] were observed in the first samples from reinfection using HTS. Conventional culture correlated with high abundance of an organism by HTS in all but 1 infection. In 6 of 7 infection dyads, organisms identified by culture at reinfection were detected by HTS of culture-negative samples at the end of the previous infection. The median Chao-Jaccard abundance-based similarity index for matched infection pairs at end of infection and beginning of reinfection was 0.57 (IQR 0.07-0.87) compared to that for unmatched pairs of 0.40 (IQR 0.10-0.60) [p = 0.46].Conclusion(s)HTS results were generally consistent with culture-based methods in CSF shunt infection and reinfection, and may detect organisms missed by culture at the end of infection treatment but detected by culture at reinfection. However, the CSF microbiota did not correlate more closely within patients at the end of infection and beginning of reinfection than between any two unrelated infections. We cannot reject the hypothesis that sequential infections were independent.
Project description:BackgroundFirst-generation cephalosporins (such as cefazolin) are recommended as antibiotic prophylaxis in groin hernia repair, but other broad-spectrum antibiotics have also been prescribed in clinical practice. This was a systematic review and network meta-analysis to compare the efficacy of different antibiotic classes for prevention of surgical-site infection (SSI) after hernia repair.MethodsRCTs were identified that compared efficacy of antibiotic prophylaxis on SSI after inguinal or femoral hernia repair from PubMed and Scopus databases up to March 2016. Data were extracted independently by two reviewers. Network meta-analysis was applied to assess treatment efficacy. The probability of being the best antibiotic prophylaxis was estimated using surface under the cumulative ranking curve (SUCRA) analysis.ResultsFifteen RCTs (5159 patients) met the inclusion criteria. Interventions were first-generation (7 RCTs, 1237 patients) and second-generation (2 RCTs, 532) cephalosporins, β-lactam/β-lactamase inhibitors (6 RCTs, 619) and fluoroquinolones (2 RCTs, 581), with placebo as the most common comparator (14 RCTs, 2190). A network meta-analysis showed that β-lactam/β-lactamase inhibitors and first-generation cephalosporins were significantly superior to placebo, with a pooled risk ratio of 0·44 (95 per cent c.i. 0·25 to 0·75) and 0·62 (0·42 to 0·92) respectively. However, none of the antibiotic classes was significantly different from the others. SUCRA results indicated that β-lactam/β-lactamase inhibitors and first-generation cephalosporins were ranked first and second respectively for best prophylaxis.Conclusionβ-Lactam/β-lactamase inhibitors followed by first-generation cephalosporins ranked as the most effective SSI prophylaxis for adult patients undergoing groin hernia repair.
Project description:Background: The anterior transpetrosal approach (ATPA) is effective for reaching petroclival lesions, and it allows for complications such as impaired venous return and neuropathy to be resolved. However, there is still room for improvement regarding cerebrospinal fluid (CSF) leakage. Here, we aim to focus on describing specific preoperative, intraoperative, and postoperative countermeasures for preventing CSF leakage when using the ATPA. Methods: Eleven patients treated using the ATPA, who were treated at our hospital from June 2019 to February 2023, were included in this descriptive study. Preoperatively, we performed a 3D simulation of the opened air cells. Then, we classified patterns of dural closure into three types based on intradural manipulation and whether it involved opened air cells or not. Intraoperatively, we performed a dural closure that included the use of more-watertight sutures (DuraGen®) and an endoscope. Furthermore, temporal bone air cell volume measurements were performed to confirm the correlation between the volume and factors related to CSF leakage. Results: No postoperative CSF leakage was observed in any patient. The temporal bone air cell volumes significantly corelated with the air cells of the petrous apex, the high-risk tract in the petrous apex, and postoperative fluid collection in mastoid air cells. Conclusions: We have described countermeasures for preventing CSF leakage when using the ATPA. Preoperative simulations and the use of multiple-layered dural reconstructions with endoscopes could be considered more reliable methods for preventing CSF leakage when using the ATPA.