Center enrollment:
We are currently recruiting more centers to take part in the biobank. Figure 1 demonstrates the process by which a new center is enrolled. Before a principal investigator contacts us, they should confirm that a clinical coordinator or research assistant on their team has time available to conduct the retrospective chart review and data entry for each patient from whom a sample is collected. Additional responsibilities of a center include training personnel to prepare the samples and send shipments. Once it has been established that the new center has the personnel resources to join, we provide them with a copy of the IRB proposal so that they may submit a version to their local ethics board. Next, material transfer agreements (MTA) are filled out with both the new center and WSU. Many local centers require separate MTAs for the clinical data and the shunt samples. Next, the new center often requires a data usage agreement to be completed. Finally, once WSU has a record of the new center’s IRB approval and the MTAs on file, we submit an amendment to our IRB protocol to add the new center.
Once the center is enrolled, we provide training to the personnel assigned to the project. This training includes how to use REDCap and a detailed explanation of all variables being collected. We also provide logistic support, sterile PFA, and sample containers. We conduct reviews of the database in a quality control effort to catch potential mistakes before they have been repeated.
We have formal agreements with 6 centers currently in place. The data in this paper comes from 4 centers: WSU, WUSM, TEX, and RC. The other centers, ALA and JHU, had not contributed samples at the time of analyses. Even if a center is unable to provide the clinical data associated with shunts, we invite centers to send us failed shunts that would otherwise be discarded. These samples can be used in testing new reagents and methods.
Current Biobank Content:
Across these 4 centers, to date we have enrolled 228 patients, from whom 295 samples have been collected (Table 1); the majority come from WSU and WUSM. 221 out of 295 (74.9%) samples collected contain a proximal catheter. 75 samples include a proximal catheter and another shunt component, while 146 are proximal catheters alone. We also have several subdural-catheters, EVDs, valves, reservoirs, peritoneal catheters, atrial catheters, and lumbar catheters. We have CSF associated with 76 samples, the entirety of which is from WSU and WUSM.
Table 1: Types of Samples in the Biobank | Center |
| WSU | WUSM | TEX | RC | Total |
Number of patients | 73 | 109 | 34 | 12 | 228 |
Number of samples | 115 | 132 | 34 | 14 | 295 |
Number of samples associated with CSF | 40 | 36 | - | - | 76 |
Mean samples per patient | 1.58 | 1.21 | 1.00 | 1.17 | 1.29 |
Sample Breakdown By Hardware Type |
Ventricular catheter only | 100 | 13 | 26 | 7 | 146 |
Valve only | 1 | 18 | 3 | 1 | 23 |
Peritoneal catheter only | 1 | 4 | 3 | - | 8 |
Other (reservoir only, EVD only, other combinations) | 13 | 97 | 2 | 6 | 118 |
Samples which include a ventricular catheter | 101 | 81 | 28 | 11 | 221 |
Number of samples per year |
2015 | 1 | 24 | - | - | 25 |
2016 | 49 | 15 | - | - | 64 |
2017 | 32 | 27 | 1 | - | 69 |
2018 | 28 | 37 | 23 | 1 | 89 |
2019 | 5 | 29 | 10 | 13 | 57 |
The demographics of the patients already enrolled (Table 2) show a prevalence of males; however, this was not statistically significant. The total percentage of African American patients was significantly different when compared to the general population (chi-square p = 0.001291); however, this significance disappears when controlling for the percentage of African Americans in the metropolitan areas our hospitals serve (chi-square p = 0.827754). Patient age was significantly different between the sites (Kruskal-Wallis H test p = 0.000003).
Table 2: Demographics of Patients with Samples in the Biobank | Center |
WSU | WUSM | TEX | RC | Total |
Biologic Sex | Male | 45 | 53 | 21 | 5 | 124 |
Female | 28 | 54 | 13 | 7 | 102 |
Other | - | 2 | - | - | 2 |
Race | White | 32 | 89 | 29 | 9 | 159 |
African American | 34 | 16 | 5 | 2 | 57 |
Asian | 2 | - | - | - | 2 |
American Indian/Alaska Native | - | - | - | - | - |
Native Hawaiian or Other Pacific Islander | - | - | - | 1 | 1 |
Declined/Unknown | 5 | 4 | - | - | 9 |
Ethnicity | Hispanic or Latino | 1 | 1 | 16 | 1 | 19 |
Not Hispanic or Latino | 67 | 104 | 18 | 11 | 200 |
Declined/Unknown | 5 | 4 | - | - | 9 |
Average Age at Sample collection (in years +/- SD) | 12.12 (+/- 10.39) | 6.50 (+/- 6.09) | 11.00 (+/- 5.73) | 6.90 (+/- 5.13) | 9.23 (+/- 8.39) |
Hydrocephalus History:
The most common hydrocephalous etiology (Fig. 2a) in our patient cohort was post-hemorrhagic hydrocephalus of prematurity (95 patients, 41.9%), followed by myelomeningocele (37, 16.2%), aqueductal-stenosis (18, 7.9%), brain tumors (15, 6.6%), congenital CNS malformations (12, 5.2%), communicating congenital (11, 4.8%), other (8, 3.5%), trauma (7, 3.1%), postnatal meningitis (6, 2.6%), Dandy-Walker malformation/obstructive arachnoid cyst (6, 2.6%), unknown (6, 2.6%), and congenital CNS infection (3, 1.3%). Ventriculomegaly without CNS abnormalities, craniosynostosis and pseudotumor cerebri were all under 1% of patients.
The causes for removal of the samples (Fig. 2b) are as follows: proximal catheter obstruction (121 samples, 41.2%), other (39, 13.2%), multiple reasons for removal (37, 12.5%), externalization due to infection (26, 8.7%), internalization i.e. EVD removal (20, 6.9%), valve obstruction (10, 3.5%), distal catheter obstruction (9, 3.1%), disconnection (7, 2.4%), over-drainage (6, 2.1%), truncated catheter (4, 1.4%), reservoir malfunction (4, 1.4%), and unknown (4, 1.4%). Ventriculomegaly not otherwise specified, fracture of the proximal catheter, externalization due to pseudocyst, and externalization due to other cause were the cause of removal for less than 1% of samples. Samples were placed in the ‘Multiple reasons for removal’ category when the multiple causes existed without being able to determine the root cause of the failure. Including the occurrences when there were multiple potential causes of shunt failure, 45.2% of samples were removed due to proximal catheter obstruction. Common causes grouped under ‘Other’ are switching a reservoir to a VPS, pressure sores/irritation, and wound dehiscence. When the indication for failure included infection, we cross referenced lab results to check if the patient had a positive CSF culture during their admission. Out of the 29 samples that were removed for suspected infection: 6 had negative CSF cultures, 20 had positive cultures and no cultures were ever obtained for 3. Additionally, 4 others in whom infection was not suspected pre-operatively showed positive CSF cultures.
The number of revisions prior to patient enrollment in the biobank (Fig. 2c) differed significantly between centers (Kruskal-Wallis H test p = 0.000022); the medians (and interquartile ranges) are as follows: WSU 3 (8), WUSM 1 (3), TEX 1 (1), and RC 1 (4). Pairwise comparisons (Dunn’s post hoc test) showed WSU to be significantly higher than TEX and WUSM (p = 0.003 and p < 0.000 respectively). All other comparisons were not significant. Given that age significantly varied between the centers, regression analysis was performed to test if this relationship persisted when controlling for age. Center significantly impacted the number of prior revisions even when controlling for age (p = 0.017). The number of ventricular catheter obstructions prior to enrollment (Fig. 2d) was also significantly different between centers (Kruskal Wallis H test p = 1.8241− 14). Pairwise comparison (Dunn’s post hoc test) showed WUSM to be significantly lower than TEX and WSU (p < 0.000 and p < 0.000 respectively). All other comparisons were not significant. Regression was also performed to test if this relationship persisted when controlling for age: it was found that center significantly (p = 0.00057) affected the number of ventricular catheter obstructions when controlling for age.
One other metric by which centers can be compared is the mean length of time that each ventricular catheter was implanted before failing (Fig. 3). The median lengths of insertion in months (and interquartile ranges) were as follows: WSU 5.84 (52.08), WUSM 8.97 (64.54), TEX 8.61 (55.16), and RC 8.01 (42.48). There was not a significant difference between the centers (Kruskal-Wallis H test p = 0.609).