Pediatric ventriculoperitoneal shunt failure and cerebrospinal fluid protein

Pediatric ventriculoperitoneal shunt failure and cerebrospinal fluid protein | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Pediatric ventriculoperitoneal shunt failure and cerebrospinal fluid protein Charles F Yates, Michael J Colditz, Liam Maclachlan, Martin J Wood, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5016920/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Ventriculoperitoneal shunts (VPS) are a life-saving intervention for hydrocephalus. Device failure is extremely common, and carries great morbidity for patients, their families, and the healthcare system. Predicting shunt failure remains a substantial challenge. Clinically, cerebrospinal fluid protein (CSFp) is suspected to contribute to VPS obstruction, this is widely debated, and definitive evidence is lacking. We assess the value of CSFp in predicting VPS failure due to non-infective causes. Methods: A retrospective review of VPS procedures at the Queensland Children’s Hospital between 2014-2019 was conducted. The relationship between CSFp level and outcome were explored. Outcome variables were early VPS failure (< 90-days), and late VPS failure (<1-year). A CNS infection was reason for exclusion. A logarithmic correction was applied to CSFp (Log-CSFp) for statistical modelling. Results 552 procedures were assessed in 243 patients. 87 (15.8%) VP shunts failed within 90-days, 129 (23.4%) within 1-year. 77 patients (31.7%) experienced an episode of <1-year VPS failure. Multivariate analysis found Log-CSFp was predictive for early VPS failure (OR 1.19, 1.05-1.35, p=0.005), and late VPS failure (OR 1.15, 1.01-1.32, p=0.042) independent to hydrocephalus aetiology, patient age, and CSF red blood cell count. Older patient age was a significant protective factor for early (OR 0.94, 0.89-0.99, p=0.023) and late VPS failure (OR 0.89, 0.84-0.95, p<0.0001) respectively. Conclusion CSFp holds prognostic value for VPS failure in pediatric patients, a relentlessly unpredictable complication of VPS devices, informing procedure timing, patient follow-up and risk-stratification. Hydrocephalus CSF protein obstruction ventriculoperitoneal shunt 1. Introduction Hydrocephalus affects up to 88 per 100,000 children globally [ 1 ].Ventriculoperitoneal shunt (VPS) insertion for hydrocephalus is the most performed pediatric neurosurgical procedure [ 2 ], with 85% of VPS devices failing within 15-years of placement [ 3 ], most commonly due to fouling and blockage of the VPS system [ 4 – 7 ]. Pediatric patients are at significantly increased risk of device failure compared to adults [ 4 , 5 ], and this complication carries a large burden of morbidity for patients and their families [ 6 , 8 , 9 ]. Identifying patients at high risk of VPS failure remains a substantial challenge. Factors such as young age at insertion [ 9 – 11 ], haemorrhagic aetiology for hydrocephalus [ 10 , 12 ], and CSF white blood cell count [ 9 ] have been previously been associated VPS failure. In neurosurgical practice, shunt failure commonly occurs in the context of elevated CSF protein (CSFp) [ 7 ]. However, current evidence for the role of CSFp elevation in VPS failure is equivocal [ 9 , 13 – 19 ]. Several in-vitro analyses have explored the relationship between VPS failure and CSFp with CSF albumin as a protein marker, showing no association with device failure [ 16 , 18 , 19 ]. However, albumin lacks any pro-inflammatory capacity, a fundamental pathophysiological mechanism for protein interaction with foreign devices [ 20 , 21 ]. A recent assessment of CSFp and valve-specific device failure in 285 patients described a significant association between peri-operative CSFp failure [ 9 ]. The presence of CSF proteins such as IL-4, IL-6, TNF-α, TGF-β, complement and immunoglobulins, in patients suffering hydrocephalus is well described [ 20 , 22 – 26 ]. These originate from glial activation or peripheral plasma following insult, and are particularly elevated in hydrocephalus following intraventricular haemorrhage, tumours, and post-infection aetiologies [ 22 , 25 , 26 ]. Interestingly, shunt failure is more common in these aetiologies [ 3 , 4 , 8 ]. Understanding the role CSFp plays in the aetiology of obstruction may have implications for decisions on timing of VPS insertion, clinical surveillance and, potentially, for device modification. In this study, we aim to investigate the relationship between CSFp and VPS failure in a large pediatric cohort. 2. Methods and Materials Procedures A retrospective search of the Queensland Children’s hospital’s neurosurgical department database was undertaken. Relevant data pertaining to all VPS procedures conducted between 2014 to 2019 was extracted. The study was approved by the hospital’s human research ethics committee (EX/22/QCHQ/84740, approval number: 230322), and deemed not to require individual patient consent per the committee’s low-negligible risk study guidelines. This study was conducted in accordance with the Strengthening Reporting of Observational Studies in Epidemiology (STROBE) guidelines. All patients within the pediatric range receiving a VPS procedure (revision or new insertion) were included. Patients data for a procedure was excluded if a CSF infection was present, defined as a positive CSF culture 3 days pre- or post-operatively. The primary outcomes were early VPS device failure, occurring within 90-days of a previous shunt procedure, and delayed failure within 1-year. Extracted data included patient demographics, aetiology of hydrocephalus, date of a procedure, emergency or elective procedure, number of previous VPS procedures, CSFp level, CSF red blood cell count (CSF RCC), and deceased status at last follow-up. A procedure was classified as an emergency when the patient had an acutely deteriorating clinical status and the procedure was performed non-electively. Where aetiology was classified as post-infection, this described an infectious process as a cause for hydrocephalus and not an infection at the time of CSF sampling. Vascular aetiologies included intra-ventricular haemorrhage, arteriovenous malformation rupture, aneurysmal subarachnoid haemorrhage, and traumatic haemorrhage. These were grouped to account for the shared pathophysiological mechanism of haemolysis in chronic communicating hydrocephalus. Statistical Analysis All analyses were conducted by a senior biostatistician and the investigating team. Normality of distribution was assessed using the Shapiro-Wilk test. continuous variables with a normal distribution were described using mean and standard deviation, otherwise median and inter-quartile range were employed. Multiple CSF protein samples taken within 3-days preceding a VPS procedure were averaged. CSF protein and CSF red blood cell count levels in this population had a significant right skew, therefore a logarithmic base 2 (Log 2 CSFp) correction was applied to each respectively (Log-CSFp, Log-RCC) [27]. Therefore, odds ratio’s represent an effect with doubling of CSFp or CSF RCC. Univariate binary logistic regression was used to define relationships between independent and dependent variables. Variables with an alpha <0.1 were included in multivariate analyses by mixed effects logistic regression . Relationships between independent and dependent variables was described by odds-ratio’s. 3. Results Two-hundred and fourty-five patients underwent 592 procedures in the 6-year study period. After exclusion for CSF infection, two-hundred and fourty-three patients were assessed undergoing 552 procedures. A confirmed CNS infection was recorded for 40 procedures (6.8%). Sex distribution had a male prevalence with 133 (54.7%) male patients and 110 (45.3%) female patients. Average patient age was 6.3 years (± 5.3 years), with 44 patients (18.1%) less than 1-year old. Congenital pathology was the most common aetiology (27.5%), followed by vascular pathology (26.1%) and tumours (26.1%). Over half of patients underwent a single VPS procedure in the 6-year study period (126 patients, 51.9%), 82 patients (33.7%) underwent 2 or 3 procedures and the remainder received more than 3 procedures (14.4%). Sixty patients (24.7%) experienced an episode of shunt failure less than 90-days from a shunt insertion or revision, while 77 (31.7%) patients experienced shunt failure within 1-year. On a per-procedure basis 87 VPS revisions (14.7%) occurred within 90-days, 129 (21.8%) within 1-year. Average time to shunt failure was 113.2 days (± 190.3). Emergency VPS procedures accounted for 366 (66.4%) procedures. Median CSF protein during admission was 380.0mg/L (IQR130–1400mg/L), transformed to a Log-CSFp of 8.8 mg/L (± 2.1mg/L). The median CSF RBC during admission was 160 x10 6 /L (IQR 15, 1260), transformed to a Log-RCC of 7.4 x10 6 /L (± 4.0 x10 6 /L ). Table 1 Cohort characteristics of patients undergoing ventriculoperitoneal shunt revision or insertion at the Queensland Children’s Hospital from 2014–2020. Variable Cohort, n (%) N 243 Male: Female 133:110 Age-group (years) < 1 44 (18.1) ≥ 1 199 (81.9) Pathology group Vascular 57 (26.1) Congenital malformation 60 (27.5) Tumour 57 (26.1) Post-infection 16 (7.3) Other* 28 (12.8) Procedures per patient 1 126 (51.9) 2–3 82 (33.7) > 3 35 (14.4) Episode of < 90-day shunt failure 60 (24.7) Episode of < 1-year shunt failure 77 (31.7) Deceased at last review 22 (9.1) Procedures N 552 VP Shunt failure within 90-days 87 (15.8) VP Shunt failure within 1-year 129 (23.4) * Other included idiopathic hydrocephalus, post-traumatic or post-operative hydrocephalus 3.1 VP Shunt failure within 90-days post-insertion. VP shunt failure within 90-days was experienced by 60 patients (24.7%), who suffered 87 episodes (15.8%) within the study period. Average Log-CSFp was significantly elevated in patients suffering VPS failure within 90-days compared to those who did not, and predicted 90-days VPS failure (9.6 ± 2.3 vs 8.6 ± 2.0 mg/L, OR 1.26, 1.12–1.42, p < 0.0001). Younger patient age similarly predicted 90-day VPS failure, with older age reducing odds of 90-day failure (OR 0.92, 0.88–0.97, p = 0.001). The predictive value of Log-CSFp was retained on multivariate analysis including patient age and pathology type (OR 1.19, 1.05–1.35, p = 0.005). Older patient age similarly retained predictive value in reduced odds for 90-day VPS failure (OR 0.94, 0.89–0.99, p = 0.023). Table 2 Binary logistic regression analysis and mixed effects logistic regression multivariate analysis for 90-day ventriculoperitoneal shunt failure. N = 552 Univariate Analysis Multivariate Analysis Shunt fail < 90 days Fail % OR (95% CI) p-value OR (95% CI) p-value Log-CSFp 1.26 (1.12–1.42) < 0.0001 1.19 (1.05–1.35) 0.005 Log-RCC 1.02 (0.96–1.10) 0.422 Gender Female 23.6% 1.00 Male 20.1% 0.75 (0.48–1.19) Age ≥ 1year 0.92 (0.88–0.97) 0.001 0.94 (0.89–0.99) 0.023 Presentation type Elective 25.5% 1.00 Emergency 20.0% 0.96 (0.60–1.55) Pathology group Congenital 16.9% 1.00 1.00 Post-infective 26.7% 1.61 (0.54–4.85) 0.394 0.31 (0.04–2.57) 0.277 Tumour 23.5% 1.71 (0.86–3.38) 0.126 1.78 (0.83–3.80) 0.138 Vascular 29.9% 1.84 (0.95–3.57) 0.072 1.55 (0.71–3.37) 0.268 Other 16.2% 1.72 (0.76–3.90) 0.192 1.53 (0.61–3.80) 0.364 3.2 VP-Shunt failure within 1-year post-insertion. VP shunt failure within 1-year was experienced by 77 patients (31.7%) who suffered 129 episodes (23.4%) within the study period. Average Log-CSFp was significantly elevated in patients suffering VPS failure within 1-year compared to those who did not, and predicted 1-year VPS failure (9.4 ± 2.3 vs 8.6 ± 2.0 mg/L, OR 1.21, 1.09–1.34, p < 0.0001). 1- year VPS failure was similarly less likely with older patient age (OR 0.89, 0.85–0.94, p < 0.0001) and pathology subtype (p = 0.005). Multivariate analysis for these variables, including Log-RCC, found 1-year VPS failure was predicted by Log-CSFp (OR 1.15, 1.01–1.32, p = 0.04), pathology subtype (p = 0.045), and less likely with older patient age (OR 0.89, 0.84–0.95, p > 0.0001). Table 3 Binary logistic regression analysis and mixed effects logistic regression multivariate analysis for 1-year ventriculoperitoneal shunt failure. N = 552 Univariate Analysis Multivariate Analysis Shunt fail < 90 days Fail % OR p-value OR p-value Log-CSFp 1.21 (1.09–1.34) < 0.0001 1.15 (1.01–1.32) 0.040 Log-RCC 1.06 (1.00-1.12) 0.070 1.07 (1.00-1.15) 0.052 Gender Female 16.9% 1.00 Male 13.3% 0.82 (0.55–1.21) Age ≥ 1 year 0.89 (0.85–0.94) < 0.0001 0.89 (0.84–0.95) < 0.0001 Presentation type Elective 15.4% 1.00 Emergency 14.9% 0.73 (0.49–1.10) Pathology group Congenital 11.0% 1.00 1.00 Post-infective 16.7% 1.79 (0.71–4.51) 0.219 2.04 (0.48–8.62) 0.147 Tumour 17.6% 1.51 (0.84–2.71) 0.170 1.59 (0.73–3.50) 0.243 Vascular 18.6% 2.10 (1.20–3.67) 0.009 1.58 (0.70–3.57) 0.272 Other 17.6% 1.79 (0.71–4.50) 0.219 0.40 (0.11–1.39) 0.364 4. Discussion To our knowledge this is the largest pediatric analysis of VPS failure related to CSF biochemistry. Our rate of VPS failure is consistent with the literature and confirms that a significant cohort of patients require at least one VPS revision procedure [ 5 , 7 , 9 ] (Table 1 ) . Our data also indicates that, for every doubling in peri-operative CSFp: (1) the odds of early VPS failure within 90-days increase by 19% (Table 2 ) , and (2) the odds of delayed VPS failure within 1-year increases by 15% (Table 3 ) . Older patient age is protective for VPS failure. Despite the high incidence of VPS failure and development in our understanding of hydrocephalus, predicting device failure in clinical practice remains a challenge [ 3 , 5 ], and the value of CSFp in this respect has been debated [ 9 , 13 – 16 ]. The results herein are a valuable addition to the literature describing the potential of CSFp in predicting VPS failure. These results suggest CFSp has a role in early and late device failure, and therefore a possible sustained pathological process. Across early and late device failure, predictive value was retained on multivariate analysis for variables such as CSF RBC count, patient age, underlying aetiology, and procedure urgency. Our findings are supported by a large clinical study investigating valve-specific obstruction, finding significantly higher CSFp concentrations in early valve obstructions [ 9 ]. Similarly, a review of obstructed VPS devices for tuberculous meningitis patients described a strong relationship between CSFp and VPS obstruction [ 7 ]. Furthermore, a recent clinical study described marked elevation of inflammatory proteins IL-6, IL-8, IL-10, MMP-7, and MMP-9 in patients with higher historical incidence of VPS obstruction [ 20 ]. Other clinical cohort studies have failed to demonstrate this relationship [ 13 , 14 , 17 ]. One explanation for the difference in findings may be the impact of natural variability in CSFp on smaller cohort sizes used in these studies (33–95 patients).. In-vitro flow-studies have similarly assessed the effect of CSFp on shunt flow, using high concentration CSF-albumin [ 16 , 18 , 19 ]. They observe no difference in CSF flow and device failure with raised albumin concentrations, however albumin has no inflammatory capacity and these models do not account for the predominance of inflammatory proteins in acquired hydrocephalus [ 22 – 26 ]. Under homestatic conditions, albumin is the predominant CSF protein by approximately eight fold [ 19 ]. However, inflammatory proteins such as cytokines, immunoglobulins and complement are markeldy elevated in communicating hydrocephalus [ 18 , 19 , 22 – 25 ]. Evidence for dysregulate inflammation and glial cell activation in VPS failure is growing [ 11 , 28 – 31 ]. Multiple immunohistochemical analyses on obstructed VPS devices [ 11 , 28 – 31 ]. A recent immunohistochemical analysis described a marked local astrocyte, macrophage, and microglia presence in obstructed VPS catheters [ 11 ]. Microglia and astrocytes are intimately approximated to the proximal VPS catheter, and reactive gliosis in this pro-inflammatory environment may underly VPS fouling. Hydrocephalus aetiology is thought to affect VPS failure risk, with a higher incidence of failure in vascular aetiologies [ 32 ]. Our results demonstrate vascular aetiology held significance on univariate analysis in predicting late shunt failure, however this was not significant on multivariate analysis (Table 3 ) . CSF-RCC which holds close relation to underlying aetiology held a trend toward signifance in predicting late VPS failure (OR 1.07, 1.00-1.15, p = 0.052, Table 3 ). Vascular aetiologies may cause chronic communicating hydrocephalus by extravasation of red blood cells, followed by erythrolysis with a reactive inflammatory fibrosis at sites of CSF reabsorption such as arachnoid granulations [ 30 , 32 ]. Lysis protein products, such as haem, are pro-inflammatory and likely mediate both hydrocephalus and VPS obstruction, rather than whole erythrocytes. This may explain our finding that on multivariate analysis CSFp retains significant predictive value when adjusted for underlying aetiology. Older patient age was independently protective for odds of early and late VPS failure on multivariate analysis (Table 2 , 3 ) . This is consistent with other pediatric populations [ 33 , 34 ], in which patients less than 1-year old are significantly more likely to suffer failure. This may be accounted for by the inclusion of preterm infants, or differences in immune capacity [ 33 ]. These results define a phenomen observed in clinical practice, increased incidence in VPS failure in the setting of raised CSFp levels [ 7 ]. Factoring CSFp levels into clinical decision-making for timing of VPS insertion, may reduce the significant burden of morbidity experienced by these patients and their families. Similarly, patient follow-up and risk-stratification may be informed by our findings for patients in which CSFp is known to be elevated. Strengths and Limitations We have collected data from a large cohort of pediatric patients. We have also analysed values of CSFp collected over a sequence of days to mitigate variable CSFp levels evident across a series of single collections. While there exists cause-effect limitations inherent to our retrospective design, our results have demonstrated strong associations that catalyse the need for further investigation. Excluding cases of culture positive CSF infections was important because we were interested primarily in the failure of VPS devices for causes not-related to infection. However, 30% of VPS infections are culture negative [ 4 ], so we cannot rule out infection-related CSFp elevation in a subset of our cohort. Finally, variability in hydrocephalus aetiology by geographic and socio-economic separation is well-documented [ 22 ], This cohort represents the Australian pediatric population and external validity to other cohorts may be limited. 5. Conclusion Children with hydrocephalus necessitating a VPS insertion experience significant morbidity from device failure. This complication is extremely common and remains difficult to predict. We find that CSF protein is associated with VPS failure within 90-days and 1-year, independent of other risk factors. Our results suggest that timing of VPS insertion in relation to CSFp, and closer surveillance of VPS patients with high protein levels may be prudent. Our results highlight the need for a large, prospective multi-centre cohort study to evaluate CSFp and device failure in patients suffering hydrocephalus. Declarations Author Contribution All authors contributed to the study conception and design. Material preparation, data collection were performed by Charles F Yates, and Michael J Colditz. Statistical analysis was done by Charles F Yates with institutional biostatistics support by Dr Lee Jones. The first draft of the manuscript was written by Charles F Yates, Michael J Colditz, Liam Maclachlan. All authors commented on and aided revision of versions of the manuscript. All authors read and approved the final manuscript. Acknowledgement The authors would like to acknowledge Dr Lee Jones, Queensland Institute for Medical Research, for statistical support in final analysis. References Dewan MC, Rattani A, Mekary R, Glancz LJ, Yunusa I, Baticulon RE, Fieggen G, Wellons JC, Park KB, Warf BC (2018) Global hydrocephalus epidemiology and incidence: systematic review and meta-analysis. J Neurosurg : 1–15 Richards HK, Seeley HM, Pickard JD (2009) Efficacy of antibiotic-impregnated shunt catheters in reducing shunt infection: data from the United Kingdom Shunt Registry. J Neurosurg Pediatr 4:389–393 Stone JJ, Walker CT, Jacobson M, Phillips V, Silberstein HJ (2013) Revision rate of pediatric ventriculoperitoneal shunts after 15 years. J Neurosurg Pediatr 11:15–19 Mallucci CL, Jenkinson MD, Conroy EJ, Hartley JC, Brown M, Dalton J, Kearns T, Moitt T, Griffiths MJ, Culeddu G, Solomon T, Hughes D, Gamble C (2019) collaborators BS Antibiotic or silver versus standard ventriculoperitoneal shunts (BASICS): a multicentre, single-blinded, randomised trial and economic evaluation. Lancet 394: 1530–1539 Riva-Cambrin J, Kestle JR, Holubkov R, Butler J, Kulkarni AV, Drake J, Whitehead WE, Wellons JC 3rd, Shannon CN, Tamber MS, Limbrick DD Jr., Rozzelle C, Browd SR, Simon TD, Hydrocephalus Clinical Research N (2016) Risk factors for shunt malfunction in pediatric hydrocephalus: a multicenter prospective cohort study. J Neurosurg Pediatr 17:382–390 Mitchell KS, Zelko I, Shay T, Horen S, Williams A, Luciano M, Huang J, Brem H, Gordon CR (2021) The Impact of Hydrocephalus Shunt Devices on Quality of Life. J Craniofac Surg 32:1746–1750 Kamat AS, Gretschel A, Vlok AJ, Solomons R (2018) CSF protein concentration associated with ventriculoperitoneal shunt obstruction in tuberculous meningitis. Int J Tuberc Lung Dis 22:788–792 Iglesias S, Ros B, Ros A, Selfa A, Linares J, Rius F, Arraez MA (2021) Quality of life in school-age children with shunt implantation due to neonatal posthemorrhagic hydrocephalus. Childs Nerv Syst 37:1127–1135 Kaestner S, Sani R, Graf K, Uhl E, Godau J, Deinsberger W (2021) CSF shunt valve occlusion-does CSF protein and cell count matter? Acta Neurochir (Wien) 163:1991–1996 Tervonen J, Leinonen V, Jaaskelainen JE, Koponen S, Huttunen TJ (2017) Rate and Risk Factors for Shunt Revision in Pediatric Patients with Hydrocephalus-A Population-Based Study. World Neurosurg 101:615–622 Hariharan P, Sondheimer J, Petroj A, Gluski J, Jea A, Whitehead WE, Sood S, Ham SD, Rocque BG, Marupudi NI, McAllister JP 2nd, Limbrick D, Del Bigio MR, Harris CA (2021) A multicenter retrospective study of heterogeneous tissue aggregates obstructing ventricular catheters explanted from patients with hydrocephalus. Fluids Barriers CNS 18:33 Alvi MA, Bhandarkar AR, Daniels DJ, Miller KJ, Ahn ES (2022) Factors associated with early shunt revision within 30 days: analyses from the National Surgical Quality Improvement Program. J Neurosurg Pediatr 29:21–30 Fulkerson DH, Vachhrajani S, Bohnstedt BN, Patel NB, Patel AJ, Fox BD, Jea A, Boaz JC (2011) Analysis of the risk of shunt failure or infection related to cerebrospinal fluid cell count, protein level, and glucose levels in low-birth-weight premature infants with posthemorrhagic hydrocephalus. J Neurosurg Pediatr 7:147–151 Brydon HL, Hayward R, Harkness W, Bayston R (1996) Does the cerebrospinal fluid protein concentration increase the risk of shunt complications? Br J Neurosurg 10:267–273 Ambekar S, Dwarakanath S, Chandramouli BA, Sampath S, Devi BI, Pandey P (2011) Does CSF composition predict shunt malfunction in tuberculous meningitis? Indian J Tuberc 58:77–81 Baird C, Farner S, Mohr C, Pittman T (2002) The effects of protein, red blood cells and whole blood on PS valve function. Pediatr Neurosurg 37:186–193 Kang DH, Park J, Park SH, Kim YS, Hwang SK, Hamm IS (2010) Early ventriculoperitoneal shunt placement after severe aneurysmal subarachnoid hemorrhage: role of intraventricular hemorrhage and shunt function. Neurosurgery 66:904–908 discussion 908–909 Brydon HL, Bayston R, Hayward R, Harkness W (1996) The effect of protein and blood cells on the flow-pressure characteristics of shunts. Neurosurgery 38:498–504 discussion 505 Cheatle JT, Bowder AN, Tefft JL, Agrawal SK, Hellbusch LC (2015) Effect of Protein Concentration on the Flow of Cerebrospinal Fluid Through Shunt Tubing. Neurosurgery 77:972–978 Harris CA, Morales DM, Arshad R, McAllister JP 2nd, Limbrick DD Jr (2021) Cerebrospinal fluid biomarkers of neuroinflammation in children with hydrocephalus and shunt malfunction. Fluids Barriers CNS 18:4 Bulley S, Liu Y, Ripps H, Shen W (2013) Taurine activates delayed rectifier Kv channels via a metabotropic pathway in retinal neurons. J Physiol 591:123–132 Robert SM, Reeves BC, Marlier A, Duy PQ, DeSpenza T, Kundishora A, Kiziltug E, Singh A, Allington G, Alper SL, Kahle KT (2021) Inflammatory hydrocephalus. Child's Nerv Syst 37:3341–3353 Otun A, Morales DM, Garcia-Bonilla M, Goldberg S, Castaneyra-Ruiz L, Yan Y, Isaacs AM, Strahle JM, McAllister JP 2nd, Limbrick DD Jr (2021) Biochemical profile of human infant cerebrospinal fluid in intraventricular hemorrhage and post-hemorrhagic hydrocephalus of prematurity. Fluids Barriers CNS 18:62 Karimy JK, Zhang J, Kurland DB, Theriault BC, Duran D, Stokum JA, Furey CG, Zhou X, Mansuri MS, Montejo J, Vera A, DiLuna ML, Delpire E, Alper SL, Gunel M, Gerzanich V, Medzhitov R, Simard JM, Kahle KT (2017) Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus. Nat Med 23:997–1003 Xu H, Wang Z, Zhang S, Tan G, Zhu H (2013) Procollagen Type I C-terminal propeptide, procollagen Type III N-terminal propeptide, hyaluronic acid, and laminin in the cerebrospinal fluid of rats with communicating hydrocephalus. J Neurosurg Pediatr 11:692–696 Karimy JK, Reeves BC, Damisah E, Duy PQ, Antwi P, David W, Wang K, Schiff SJ, Limbrick DD Jr., Alper SL, Warf BC, Nedergaard M, Simard JM, Kahle KT (2020) Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets. Nat Rev Neurol 16:285–296 West RM (2022) Best practice in statistics: The use of log transformation. Ann Clin Biochem 59:162–165 Boch AL, Hermelin E, Sainte-Rose C, Sgouros S (1998) Mechanical dysfunction of ventriculoperitoneal shunts caused by calcification of the silicone rubber catheter. J Neurosurg 88:975–982 Hanak BW, Ross EF, Harris CA, Browd SR, Shain W (2016) Toward a better understanding of the cellular basis for cerebrospinal fluid shunt obstruction: report on the construction of a bank of explanted hydrocephalus devices. J Neurosurg Pediatr 18:213–223 Ludwig HC, Reitemeyer M, Bock HC, Sigler M (2020) Hydrocephalus shunt therapy: current titanium shunt valve implants obstructed by internal tissue proliferations identified as extracellular matrix membranes. Childs Nerv Syst 36:2717–2724 Sarkiss CA, Sarkar R, Yong W, Lazareff JA (2014) Time dependent pattern of cellular characteristics causing ventriculoperitoneal shunt failure in children. Clin Neurol Neurosurg 127:30–32 Notarianni C, Vannemreddy P, Caldito G, Bollam P, Wylen E, Willis B, Nanda A (2009) Congenital hydrocephalus and ventriculoperitoneal shunts: influence of etiology and programmable shunts on revisions. J Neurosurg Pediatr 4:547–552 Limwattananon P, Kitkhuandee A (2021) Ventriculoperitoneal shunt failure in pediatric patients: an analysis of a national hospitalization database in Thailand. J Neurosurg Pediatr 28:128–138 McGirt M, Leveque J, Wellons J (2002) Cerebrospinal fluid shunt survival and etiology of failures: a seven-year institutional experience. Pediatr Neurosurg 36:248–255 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5016920","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":361860098,"identity":"bfb04863-f281-48d7-984e-efe834bbc65b","order_by":0,"name":"Charles F Yates","email":"data:image/png;base64,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","orcid":"","institution":"Royal Brisbane and Women’s Hospital","correspondingAuthor":true,"prefix":"","firstName":"Charles","middleName":"F","lastName":"Yates","suffix":""},{"id":361860099,"identity":"1e0d2d2c-c8d0-4c81-bd60-6027422ae236","order_by":1,"name":"Michael J Colditz","email":"","orcid":"","institution":"Royal Brisbane and Women’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"J","lastName":"Colditz","suffix":""},{"id":361860100,"identity":"fc61f1cb-413d-4d80-9f31-07f09f00462c","order_by":2,"name":"Liam Maclachlan","email":"","orcid":"","institution":"The University of Queensland","correspondingAuthor":false,"prefix":"","firstName":"Liam","middleName":"","lastName":"Maclachlan","suffix":""},{"id":361860101,"identity":"61cc6549-e5ff-4a10-ba4d-00bef1ce0159","order_by":3,"name":"Martin J Wood","email":"","orcid":"","institution":"Queensland Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Martin","middleName":"J","lastName":"Wood","suffix":""},{"id":361860102,"identity":"59575d7e-2725-495f-97c0-e8f7e5413427","order_by":4,"name":"Norman Ma","email":"","orcid":"","institution":"Royal Brisbane and Women’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Norman","middleName":"","lastName":"Ma","suffix":""},{"id":361860103,"identity":"55ee5084-5dc2-4bd8-82e9-13342d1e32a2","order_by":5,"name":"Amelia Jardim","email":"","orcid":"","institution":"Queensland Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Amelia","middleName":"","lastName":"Jardim","suffix":""},{"id":361860104,"identity":"43407951-d818-4a93-a744-d994820cfe14","order_by":6,"name":"Raymond Chaseling","email":"","orcid":"","institution":"Queensland Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Raymond","middleName":"","lastName":"Chaseling","suffix":""},{"id":361860105,"identity":"22432e1d-f01e-47f9-b0d8-6bfd220b9561","order_by":7,"name":"Robert Campbell","email":"","orcid":"","institution":"Queensland Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"","lastName":"Campbell","suffix":""}],"badges":[],"createdAt":"2024-09-02 09:09:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5016920/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5016920/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":67375942,"identity":"6502fb8e-29d5-4854-a610-de75786c640a","added_by":"auto","created_at":"2024-10-24 08:39:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":511617,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5016920/v1/c7437b87-abbd-4f5e-aedc-d6c82c918da9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pediatric ventriculoperitoneal shunt failure and cerebrospinal fluid protein","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eHydrocephalus affects up to 88 per 100,000 children globally [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].Ventriculoperitoneal shunt (VPS) insertion for hydrocephalus is the most performed pediatric neurosurgical procedure [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], with 85% of VPS devices failing within 15-years of placement [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], most commonly due to fouling and blockage of the VPS system [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Pediatric patients are at significantly increased risk of device failure compared to adults [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and this complication carries a large burden of morbidity for patients and their families [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIdentifying patients at high risk of VPS failure remains a substantial challenge. Factors such as young age at insertion [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], haemorrhagic aetiology for hydrocephalus [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and CSF white blood cell count [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] have been previously been associated VPS failure. In neurosurgical practice, shunt failure commonly occurs in the context of elevated CSF protein (CSFp) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, current evidence for the role of CSFp elevation in VPS failure is equivocal [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14 CR15 CR16 CR17 CR18\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Several in-vitro analyses have explored the relationship between VPS failure and CSFp with CSF albumin as a protein marker, showing no association with device failure [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, albumin lacks any pro-inflammatory capacity, a fundamental pathophysiological mechanism for protein interaction with foreign devices [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. A recent assessment of CSFp and valve-specific device failure in 285 patients described a significant association between peri-operative CSFp failure [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe presence of CSF proteins such as IL-4, IL-6, TNF-α, TGF-β, complement and immunoglobulins, in patients suffering hydrocephalus is well described [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan additionalcitationids=\"CR23 CR24 CR25\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. These originate from glial activation or peripheral plasma following insult, and are particularly elevated in hydrocephalus following intraventricular haemorrhage, tumours, and post-infection aetiologies [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Interestingly, shunt failure is more common in these aetiologies [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eUnderstanding the role CSFp plays in the aetiology of obstruction may have implications for decisions on timing of VPS insertion, clinical surveillance and, potentially, for device modification. In this study, we aim to investigate the relationship between CSFp and VPS failure in a large pediatric cohort.\u003c/p\u003e"},{"header":"2. Methods and Materials","content":"\u003ch3\u003eProcedures\u003c/h3\u003e\n\u003cp\u003eA retrospective search of the Queensland Children\u0026rsquo;s hospital\u0026rsquo;s neurosurgical department database was undertaken. Relevant data pertaining to all VPS procedures conducted between 2014 to 2019 was extracted. The study was approved by the hospital\u0026rsquo;s human research ethics committee (EX/22/QCHQ/84740, approval number: 230322), and deemed not to require individual patient consent per the committee\u0026rsquo;s low-negligible risk study guidelines. This study was conducted in accordance with the Strengthening Reporting of Observational Studies in Epidemiology (STROBE) guidelines. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll patients within the pediatric range receiving a VPS procedure (revision or new insertion) were included. Patients data for a procedure was excluded if a CSF infection was present, defined as a positive CSF culture 3 days pre- or post-operatively. The primary outcomes were early VPS device failure, occurring within 90-days of a previous shunt procedure, and delayed failure within 1-year. Extracted data included patient demographics, aetiology of hydrocephalus, date of a procedure, emergency or elective procedure, number of previous VPS procedures, CSFp level, CSF red blood cell count (CSF RCC), and deceased status at last follow-up. A procedure was classified as an emergency when the patient had an acutely deteriorating clinical status and the procedure was performed non-electively. Where aetiology was classified as post-infection, this described an infectious process as a cause for hydrocephalus and not an infection at the time of CSF sampling. Vascular aetiologies included intra-ventricular haemorrhage, arteriovenous malformation rupture, aneurysmal subarachnoid haemorrhage, and traumatic haemorrhage. These were grouped to account for the shared pathophysiological mechanism of haemolysis in chronic communicating hydrocephalus. \u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eStatistical Analysis\u003c/h3\u003e\n\u003cp\u003eAll analyses were conducted by a senior biostatistician and the investigating team. Normality of \u0026nbsp; distribution was assessed using the Shapiro-Wilk test. continuous variables with a normal distribution were described using mean and standard deviation, otherwise median and inter-quartile range were employed. Multiple CSF protein samples taken within 3-days preceding a VPS procedure were averaged. CSF protein and CSF red blood cell count levels in this population had a significant right skew, therefore a logarithmic base 2 (Log\u003csub\u003e2\u003c/sub\u003eCSFp) correction was applied to each respectively (Log-CSFp, Log-RCC) [27]. Therefore, odds ratio\u0026rsquo;s represent an effect with doubling of CSFp or CSF RCC. Univariate binary logistic regression was used to define relationships between independent and dependent variables. Variables with an alpha \u0026lt;0.1 were included in multivariate analyses by mixed effects logistic regression . Relationships between independent and dependent variables was described by odds-ratio\u0026rsquo;s.\u0026nbsp;\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eTwo-hundred and fourty-five patients underwent 592 procedures in the 6-year study period. After exclusion for CSF infection, two-hundred and fourty-three patients were assessed undergoing 552 procedures. A confirmed CNS infection was recorded for 40 procedures (6.8%). Sex distribution had a male prevalence with 133 (54.7%) male patients and 110 (45.3%) female patients. Average patient age was 6.3 years (\u0026plusmn;\u0026thinsp;5.3 years), with 44 patients (18.1%) less than 1-year old. Congenital pathology was the most common aetiology (27.5%), followed by vascular pathology (26.1%) and tumours (26.1%). Over half of patients underwent a single VPS procedure in the 6-year study period (126 patients, 51.9%), 82 patients (33.7%) underwent 2 or 3 procedures and the remainder received more than 3 procedures (14.4%). Sixty patients (24.7%) experienced an episode of shunt failure less than 90-days from a shunt insertion or revision, while 77 (31.7%) patients experienced shunt failure within 1-year. On a per-procedure basis 87 VPS revisions (14.7%) occurred within 90-days, 129 (21.8%) within 1-year. Average time to shunt failure was 113.2 days (\u0026plusmn;\u0026thinsp;190.3). Emergency VPS procedures accounted for 366 (66.4%) procedures. Median CSF protein during admission was 380.0mg/L (IQR130\u0026ndash;1400mg/L), transformed to a Log-CSFp of 8.8 mg/L (\u0026plusmn;\u0026thinsp;2.1mg/L). The median CSF RBC during admission was 160 x10\u003csup\u003e6\u003c/sup\u003e/L (IQR 15, 1260), transformed to a Log-RCC of 7.4 x10\u003csup\u003e6\u003c/sup\u003e/L (\u0026plusmn;\u0026thinsp;4.0 x10\u003csup\u003e6\u003c/sup\u003e/L ).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCohort characteristics of patients undergoing ventriculoperitoneal shunt revision or insertion at the Queensland Children\u0026rsquo;s Hospital from 2014\u0026ndash;2020.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCohort, n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e243\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMale: Female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e133:110\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge-group (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (18.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e199 (81.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePathology group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVascular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 (26.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCongenital malformation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (27.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTumour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 (26.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePost-infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (7.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOther*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (12.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eProcedures per patient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e126 (51.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82 (33.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (14.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEpisode of \u0026lt;\u0026thinsp;90-day shunt failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (24.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEpisode of \u0026lt;\u0026thinsp;1-year shunt failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77 (31.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDeceased at last review\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (9.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eProcedures\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e552\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVP Shunt failure within 90-days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87 (15.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVP Shunt failure within 1-year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e129 (23.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e*\u003cem\u003eOther included idiopathic hydrocephalus, post-traumatic or post-operative hydrocephalus\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e3.1 VP Shunt failure within 90-days post-insertion.\u003c/h2\u003e \u003cp\u003eVP shunt failure within 90-days was experienced by 60 patients (24.7%), who suffered 87 episodes (15.8%) within the study period. Average Log-CSFp was significantly elevated in patients suffering VPS failure within 90-days compared to those who did not, and predicted 90-days VPS failure (9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3 vs 8.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0 mg/L, OR 1.26, 1.12\u0026ndash;1.42, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Younger patient age similarly predicted 90-day VPS failure, with older age reducing odds of 90-day failure (OR 0.92, 0.88\u0026ndash;0.97, p\u0026thinsp;=\u0026thinsp;0.001). The predictive value of Log-CSFp was retained on multivariate analysis including patient age and pathology type (OR 1.19, 1.05\u0026ndash;1.35, p\u0026thinsp;=\u0026thinsp;0.005). Older patient age similarly retained predictive value in reduced odds for 90-day VPS failure (OR 0.94, 0.89\u0026ndash;0.99, p\u0026thinsp;=\u0026thinsp;0.023).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBinary logistic regression analysis and mixed effects logistic regression multivariate analysis for 90-day ventriculoperitoneal shunt failure.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;552\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eUnivariate Analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c10\" namest=\"c6\"\u003e \u003cp\u003eMultivariate Analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c11\" namest=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShunt fail\u0026thinsp;\u0026lt;\u0026thinsp;90 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFail %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLog-CSFp\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.26 (1.12\u0026ndash;1.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e1.19 (1.05\u0026ndash;1.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLog-RCC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.02 (0.96\u0026ndash;1.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.422\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.75 (0.48\u0026ndash;1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;1year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.92 (0.88\u0026ndash;0.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e0.94 (0.89\u0026ndash;0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresentation type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmergency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.96 (0.60\u0026ndash;1.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathology group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCongenital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-infective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.61 (0.54\u0026ndash;4.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.394\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e0.31 (0.04\u0026ndash;2.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.277\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.71 (0.86\u0026ndash;3.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e1.78 (0.83\u0026ndash;3.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.84 (0.95\u0026ndash;3.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e1.55 (0.71\u0026ndash;3.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.72 (0.76\u0026ndash;3.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.192\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e1.53 (0.61\u0026ndash;3.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.364\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e3.2 VP-Shunt failure within 1-year post-insertion.\u003c/h2\u003e \u003cp\u003eVP shunt failure within 1-year was experienced by 77 patients (31.7%) who suffered 129 episodes (23.4%) within the study period. Average Log-CSFp was significantly elevated in patients suffering VPS failure within 1-year compared to those who did not, and predicted 1-year VPS failure (9.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3 vs 8.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0 mg/L, OR 1.21, 1.09\u0026ndash;1.34, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). 1- year VPS failure was similarly less likely with older patient age (OR 0.89, 0.85\u0026ndash;0.94, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and pathology subtype (p\u0026thinsp;=\u0026thinsp;0.005). Multivariate analysis for these variables, including Log-RCC, found 1-year VPS failure was predicted by Log-CSFp (OR 1.15, 1.01\u0026ndash;1.32, p\u0026thinsp;=\u0026thinsp;0.04), pathology subtype (p\u0026thinsp;=\u0026thinsp;0.045), and less likely with older patient age (OR 0.89, 0.84\u0026ndash;0.95, p\u0026thinsp;\u0026gt;\u0026thinsp;0.0001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBinary logistic regression analysis and mixed effects logistic regression multivariate analysis for 1-year ventriculoperitoneal shunt failure.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;552\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnivariate Analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eMultivariate Analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShunt fail\u0026thinsp;\u0026lt;\u0026thinsp;90 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFail %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLog-CSFp\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.21 (1.09\u0026ndash;1.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.15 (1.01\u0026ndash;1.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.040\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLog-RCC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.06 (1.00-1.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.070\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.07 (1.00-1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.82 (0.55\u0026ndash;1.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;1 year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.89 (0.85\u0026ndash;0.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.89 (0.84\u0026ndash;0.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresentation type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmergency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.73 (0.49\u0026ndash;1.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathology group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCongenital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-infective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.79 (0.71\u0026ndash;4.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.219\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.04 (0.48\u0026ndash;8.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.51 (0.84\u0026ndash;2.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.59 (0.73\u0026ndash;3.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.10 (1.20\u0026ndash;3.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.58 (0.70\u0026ndash;3.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.272\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.79 (0.71\u0026ndash;4.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.219\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.40 (0.11\u0026ndash;1.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.364\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eTo our knowledge this is the largest pediatric analysis of VPS failure related to CSF biochemistry. Our rate of VPS failure is consistent with the literature and confirms that a significant cohort of patients require at least one VPS revision procedure [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e] (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cem\u003e)\u003c/em\u003e. Our data also indicates that, for every doubling in peri-operative CSFp: (1) the odds of early VPS failure within 90-days increase by 19% (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cem\u003e)\u003c/em\u003e, and (2) the odds of delayed VPS failure within 1-year increases by 15% (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cem\u003e)\u003c/em\u003e. Older patient age is protective for VPS failure. Despite the high incidence of VPS failure and development in our understanding of hydrocephalus, predicting device failure in clinical practice remains a challenge [\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e], and the value of CSFp in this respect has been debated [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]. The results herein are a valuable addition to the literature describing the potential of CSFp in predicting VPS failure.\u003c/p\u003e\n\u003cp\u003eThese results suggest CFSp has a role in early and late device failure, and therefore a possible sustained pathological process. Across early and late device failure, predictive value was retained on multivariate analysis for variables such as CSF RBC count, patient age, underlying aetiology, and procedure urgency. Our findings are supported by a large clinical study investigating valve-specific obstruction, finding significantly higher CSFp concentrations in early valve obstructions [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]. Similarly, a review of obstructed VPS devices for tuberculous meningitis patients described a strong relationship between CSFp and VPS obstruction [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e]. Furthermore, a recent clinical study described marked elevation of inflammatory proteins IL-6, IL-8, IL-10, MMP-7, and MMP-9 in patients with higher historical incidence of VPS obstruction [\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]. Other clinical cohort studies have failed to demonstrate this relationship [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]. One explanation for the difference in findings may be the impact of natural variability in CSFp on smaller cohort sizes used in these studies (33\u0026ndash;95 patients).. In-vitro flow-studies have similarly assessed the effect of CSFp on shunt flow, using high concentration CSF-albumin [\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. They observe no difference in CSF flow and device failure with raised albumin concentrations, however albumin has no inflammatory capacity and these models do not account for the predominance of inflammatory proteins in acquired hydrocephalus [\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]. Under homestatic conditions, albumin is the predominant CSF protein by approximately eight fold [\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, inflammatory proteins such as cytokines, immunoglobulins and complement are markeldy elevated in communicating hydrocephalus [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]. Evidence for dysregulate inflammation and glial cell activation in VPS failure is growing [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e]. Multiple immunohistochemical analyses on obstructed VPS devices [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e]. A recent immunohistochemical analysis described a marked local astrocyte, macrophage, and microglia presence in obstructed VPS catheters [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]. Microglia and astrocytes are intimately approximated to the proximal VPS catheter, and reactive gliosis in this pro-inflammatory environment may underly VPS fouling.\u003c/p\u003e\n\u003cp\u003eHydrocephalus aetiology is thought to affect VPS failure risk, with a higher incidence of failure in vascular aetiologies [\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e]. Our results demonstrate vascular aetiology held significance on univariate analysis in predicting late shunt failure, however this was not significant on multivariate analysis (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cem\u003e)\u003c/em\u003e. CSF-RCC which holds close relation to underlying aetiology held a trend toward signifance in predicting late VPS failure (OR 1.07, 1.00-1.15, p\u0026thinsp;=\u0026thinsp;0.052, Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Vascular aetiologies may cause chronic communicating hydrocephalus by extravasation of red blood cells, followed by erythrolysis with a reactive inflammatory fibrosis at sites of CSF reabsorption such as arachnoid granulations [\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e]. Lysis protein products, such as haem, are pro-inflammatory and likely mediate both hydrocephalus and VPS obstruction, rather than whole erythrocytes. This may explain our finding that on multivariate analysis CSFp retains significant predictive value when adjusted for underlying aetiology.\u003c/p\u003e\n\u003cp\u003eOlder patient age was independently protective for odds of early and late VPS failure on multivariate analysis (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cem\u003e)\u003c/em\u003e. This is consistent with other pediatric populations [\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e], in which patients less than 1-year old are significantly more likely to suffer failure. This may be accounted for by the inclusion of preterm infants, or differences in immune capacity [\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThese results define a phenomen observed in clinical practice, increased incidence in VPS failure in the setting of raised CSFp levels [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e]. Factoring CSFp levels into clinical decision-making for timing of VPS insertion, may reduce the significant burden of morbidity experienced by these patients and their families. Similarly, patient follow-up and risk-stratification may be informed by our findings for patients in which CSFp is known to be elevated.\u003c/p\u003e\n\u003ch2\u003eStrengths and Limitations\u003c/h2\u003e\n\u003cp\u003eWe have collected data from a large cohort of pediatric patients. We have also analysed values of CSFp collected over a sequence of days to mitigate variable CSFp levels evident across a series of single collections. While there exists cause-effect limitations inherent to our retrospective design, our results have demonstrated strong associations that catalyse the need for further investigation. Excluding cases of culture positive CSF infections was important because we were interested primarily in the failure of VPS devices for causes not-related to infection. However, 30% of VPS infections are culture negative [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e], so we cannot rule out infection-related CSFp elevation in a subset of our cohort. Finally, variability in hydrocephalus aetiology by geographic and socio-economic separation is well-documented [\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e], This cohort represents the Australian pediatric population and external validity to other cohorts may be limited.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eChildren with hydrocephalus necessitating a VPS insertion experience significant morbidity from device failure. This complication is extremely common and remains difficult to predict. We find that CSF protein is associated with VPS failure within 90-days and 1-year, independent of other risk factors. Our results suggest that timing of VPS insertion in relation to CSFp, and closer surveillance of VPS patients with high protein levels may be prudent. Our results highlight the need for a large, prospective multi-centre cohort study to evaluate CSFp and device failure in patients suffering hydrocephalus.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection were performed by Charles F Yates, and Michael J Colditz. Statistical analysis was done by Charles F Yates with institutional biostatistics support by Dr Lee Jones. The first draft of the manuscript was written by Charles F Yates, Michael J Colditz, Liam Maclachlan. All authors commented on and aided revision of versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors would like to acknowledge Dr Lee Jones, Queensland Institute for Medical Research, for statistical support in final analysis.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDewan MC, Rattani A, Mekary R, Glancz LJ, Yunusa I, Baticulon RE, Fieggen G, Wellons JC, Park KB, Warf BC (2018) Global hydrocephalus epidemiology and incidence: systematic review and meta-analysis. J Neurosurg : 1\u0026ndash;15\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRichards HK, Seeley HM, Pickard JD (2009) Efficacy of antibiotic-impregnated shunt catheters in reducing shunt infection: data from the United Kingdom Shunt Registry. J Neurosurg Pediatr 4:389\u0026ndash;393\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStone JJ, Walker CT, Jacobson M, Phillips V, Silberstein HJ (2013) Revision rate of pediatric ventriculoperitoneal shunts after 15 years. J Neurosurg Pediatr 11:15\u0026ndash;19\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMallucci CL, Jenkinson MD, Conroy EJ, Hartley JC, Brown M, Dalton J, Kearns T, Moitt T, Griffiths MJ, Culeddu G, Solomon T, Hughes D, Gamble C (2019) collaborators BS Antibiotic or silver versus standard ventriculoperitoneal shunts (BASICS): a multicentre, single-blinded, randomised trial and economic evaluation. Lancet 394: 1530\u0026ndash;1539\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRiva-Cambrin J, Kestle JR, Holubkov R, Butler J, Kulkarni AV, Drake J, Whitehead WE, Wellons JC 3rd, Shannon CN, Tamber MS, Limbrick DD Jr., Rozzelle C, Browd SR, Simon TD, Hydrocephalus Clinical Research N (2016) Risk factors for shunt malfunction in pediatric hydrocephalus: a multicenter prospective cohort study. J Neurosurg Pediatr 17:382\u0026ndash;390\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMitchell KS, Zelko I, Shay T, Horen S, Williams A, Luciano M, Huang J, Brem H, Gordon CR (2021) The Impact of Hydrocephalus Shunt Devices on Quality of Life. J Craniofac Surg 32:1746\u0026ndash;1750\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKamat AS, Gretschel A, Vlok AJ, Solomons R (2018) CSF protein concentration associated with ventriculoperitoneal shunt obstruction in tuberculous meningitis. Int J Tuberc Lung Dis 22:788\u0026ndash;792\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIglesias S, Ros B, Ros A, Selfa A, Linares J, Rius F, Arraez MA (2021) Quality of life in school-age children with shunt implantation due to neonatal posthemorrhagic hydrocephalus. Childs Nerv Syst 37:1127\u0026ndash;1135\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaestner S, Sani R, Graf K, Uhl E, Godau J, Deinsberger W (2021) CSF shunt valve occlusion-does CSF protein and cell count matter? Acta Neurochir (Wien) 163:1991\u0026ndash;1996\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTervonen J, Leinonen V, Jaaskelainen JE, Koponen S, Huttunen TJ (2017) Rate and Risk Factors for Shunt Revision in Pediatric Patients with Hydrocephalus-A Population-Based Study. World Neurosurg 101:615\u0026ndash;622\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHariharan P, Sondheimer J, Petroj A, Gluski J, Jea A, Whitehead WE, Sood S, Ham SD, Rocque BG, Marupudi NI, McAllister JP 2nd, Limbrick D, Del Bigio MR, Harris CA (2021) A multicenter retrospective study of heterogeneous tissue aggregates obstructing ventricular catheters explanted from patients with hydrocephalus. Fluids Barriers CNS 18:33\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlvi MA, Bhandarkar AR, Daniels DJ, Miller KJ, Ahn ES (2022) Factors associated with early shunt revision within 30 days: analyses from the National Surgical Quality Improvement Program. J Neurosurg Pediatr 29:21\u0026ndash;30\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFulkerson DH, Vachhrajani S, Bohnstedt BN, Patel NB, Patel AJ, Fox BD, Jea A, Boaz JC (2011) Analysis of the risk of shunt failure or infection related to cerebrospinal fluid cell count, protein level, and glucose levels in low-birth-weight premature infants with posthemorrhagic hydrocephalus. J Neurosurg Pediatr 7:147\u0026ndash;151\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrydon HL, Hayward R, Harkness W, Bayston R (1996) Does the cerebrospinal fluid protein concentration increase the risk of shunt complications? Br J Neurosurg 10:267\u0026ndash;273\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmbekar S, Dwarakanath S, Chandramouli BA, Sampath S, Devi BI, Pandey P (2011) Does CSF composition predict shunt malfunction in tuberculous meningitis? Indian J Tuberc 58:77\u0026ndash;81\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaird C, Farner S, Mohr C, Pittman T (2002) The effects of protein, red blood cells and whole blood on PS valve function. Pediatr Neurosurg 37:186\u0026ndash;193\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKang DH, Park J, Park SH, Kim YS, Hwang SK, Hamm IS (2010) Early ventriculoperitoneal shunt placement after severe aneurysmal subarachnoid hemorrhage: role of intraventricular hemorrhage and shunt function. Neurosurgery 66:904\u0026ndash;908 discussion 908\u0026ndash;909\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrydon HL, Bayston R, Hayward R, Harkness W (1996) The effect of protein and blood cells on the flow-pressure characteristics of shunts. Neurosurgery 38:498\u0026ndash;504 discussion 505\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheatle JT, Bowder AN, Tefft JL, Agrawal SK, Hellbusch LC (2015) Effect of Protein Concentration on the Flow of Cerebrospinal Fluid Through Shunt Tubing. Neurosurgery 77:972\u0026ndash;978\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarris CA, Morales DM, Arshad R, McAllister JP 2nd, Limbrick DD Jr (2021) Cerebrospinal fluid biomarkers of neuroinflammation in children with hydrocephalus and shunt malfunction. Fluids Barriers CNS 18:4\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBulley S, Liu Y, Ripps H, Shen W (2013) Taurine activates delayed rectifier Kv channels via a metabotropic pathway in retinal neurons. J Physiol 591:123\u0026ndash;132\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRobert SM, Reeves BC, Marlier A, Duy PQ, DeSpenza T, Kundishora A, Kiziltug E, Singh A, Allington G, Alper SL, Kahle KT (2021) Inflammatory hydrocephalus. Child's Nerv Syst 37:3341\u0026ndash;3353\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOtun A, Morales DM, Garcia-Bonilla M, Goldberg S, Castaneyra-Ruiz L, Yan Y, Isaacs AM, Strahle JM, McAllister JP 2nd, Limbrick DD Jr (2021) Biochemical profile of human infant cerebrospinal fluid in intraventricular hemorrhage and post-hemorrhagic hydrocephalus of prematurity. Fluids Barriers CNS 18:62\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarimy JK, Zhang J, Kurland DB, Theriault BC, Duran D, Stokum JA, Furey CG, Zhou X, Mansuri MS, Montejo J, Vera A, DiLuna ML, Delpire E, Alper SL, Gunel M, Gerzanich V, Medzhitov R, Simard JM, Kahle KT (2017) Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus. Nat Med 23:997\u0026ndash;1003\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu H, Wang Z, Zhang S, Tan G, Zhu H (2013) Procollagen Type I C-terminal propeptide, procollagen Type III N-terminal propeptide, hyaluronic acid, and laminin in the cerebrospinal fluid of rats with communicating hydrocephalus. J Neurosurg Pediatr 11:692\u0026ndash;696\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarimy JK, Reeves BC, Damisah E, Duy PQ, Antwi P, David W, Wang K, Schiff SJ, Limbrick DD Jr., Alper SL, Warf BC, Nedergaard M, Simard JM, Kahle KT (2020) Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets. Nat Rev Neurol 16:285\u0026ndash;296\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWest RM (2022) Best practice in statistics: The use of log transformation. Ann Clin Biochem 59:162\u0026ndash;165\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoch AL, Hermelin E, Sainte-Rose C, Sgouros S (1998) Mechanical dysfunction of ventriculoperitoneal shunts caused by calcification of the silicone rubber catheter. J Neurosurg 88:975\u0026ndash;982\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHanak BW, Ross EF, Harris CA, Browd SR, Shain W (2016) Toward a better understanding of the cellular basis for cerebrospinal fluid shunt obstruction: report on the construction of a bank of explanted hydrocephalus devices. J Neurosurg Pediatr 18:213\u0026ndash;223\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLudwig HC, Reitemeyer M, Bock HC, Sigler M (2020) Hydrocephalus shunt therapy: current titanium shunt valve implants obstructed by internal tissue proliferations identified as extracellular matrix membranes. Childs Nerv Syst 36:2717\u0026ndash;2724\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSarkiss CA, Sarkar R, Yong W, Lazareff JA (2014) Time dependent pattern of cellular characteristics causing ventriculoperitoneal shunt failure in children. Clin Neurol Neurosurg 127:30\u0026ndash;32\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNotarianni C, Vannemreddy P, Caldito G, Bollam P, Wylen E, Willis B, Nanda A (2009) Congenital hydrocephalus and ventriculoperitoneal shunts: influence of etiology and programmable shunts on revisions. J Neurosurg Pediatr 4:547\u0026ndash;552\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLimwattananon P, Kitkhuandee A (2021) Ventriculoperitoneal shunt failure in pediatric patients: an analysis of a national hospitalization database in Thailand. J Neurosurg Pediatr 28:128\u0026ndash;138\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcGirt M, Leveque J, Wellons J (2002) Cerebrospinal fluid shunt survival and etiology of failures: a seven-year institutional experience. Pediatr Neurosurg 36:248\u0026ndash;255\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hydrocephalus, CSF protein, obstruction, ventriculoperitoneal shunt","lastPublishedDoi":"10.21203/rs.3.rs-5016920/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5016920/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose \u003c/strong\u003eVentriculoperitoneal shunts (VPS) are a life-saving intervention for hydrocephalus. Device failure is extremely common, and carries great morbidity for patients, their families, and the healthcare system. Predicting shunt failure remains a substantial challenge. Clinically, cerebrospinal fluid protein (CSFp) is suspected to contribute to VPS obstruction, this is widely debated, and definitive evidence is lacking. We assess the value of CSFp in predicting VPS failure due to non-infective causes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e A retrospective review of VPS procedures at the Queensland Children’s Hospital between 2014-2019 was conducted. The relationship between CSFp level and outcome were explored. Outcome variables were early VPS failure (\u0026lt; 90-days), and late VPS failure (\u0026lt;1-year). A CNS infection was reason for exclusion. A logarithmic correction was applied to CSFp (Log-CSFp) for statistical modelling.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003e552 procedures were assessed in 243 patients. 87 (15.8%) VP shunts failed within 90-days, 129 (23.4%) within 1-year. 77 patients (31.7%) experienced an episode of \u0026lt;1-year VPS failure. Multivariate analysis found Log-CSFp was predictive for early VPS failure (OR 1.19, 1.05-1.35, p=0.005), and late VPS failure (OR 1.15, 1.01-1.32, p=0.042) independent to hydrocephalus aetiology, patient age, and CSF red blood cell count. Older patient age was a significant protective factor for early (OR 0.94, 0.89-0.99, p=0.023) and late VPS failure (OR 0.89, 0.84-0.95, p\u0026lt;0.0001) respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion \u003c/strong\u003eCSFp holds prognostic value for VPS failure in pediatric patients, a relentlessly unpredictable complication of VPS devices, informing procedure timing, patient follow-up and risk-stratification.\u003c/p\u003e","manuscriptTitle":"Pediatric ventriculoperitoneal shunt failure and cerebrospinal fluid protein","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-04 10:47:21","doi":"10.21203/rs.3.rs-5016920/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"200e973d-f83c-4073-a05f-2ebf87fea7b8","owner":[],"postedDate":"October 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-24T08:38:35+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-04 10:47:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5016920","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5016920","identity":"rs-5016920","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}