Postconception age at surgery as a predictor of ventriculoperitoneal shunt failure.

OBJECTIVE: The gold standard of pediatric hydrocephalus management is the ventriculoperitoneal (VP) shunt. However, VP shunts have high failure rates, and both young age and prematurity have been identified as potential risk factors for shunt failure, although neither variable describes total development at the time of surgery. This study aimed to further characterize age and shunt failure through the use of postconception age at surgery (PCAS) as well as investigate the 40-week PCAS threshold initially described in 1999. METHODS: A retrospective analysis was conducted on all first-time shunt placements at the authors' institution from 2010 to 2021. The National Surgical Quality Improvement Program (NSQIP) pediatric hydrocephalus dataset was used as a parallel analysis to ensure representativeness of the national pediatric hydrocephalus population. RESULTS: In the institutional cohort, infants with a PCAS < 40 weeks exhibited 2.4 times greater odds of shunt failure than those with a PCAS ≥ 40 weeks. In the NSQIP dataset, infants with a PCAS < 40 weeks had 1.45 times greater odds of shunt failure compared with those with a PCAS ≥ 40 weeks. CONCLUSIONS: The 40-week PCAS threshold appears to be a significant predictor of shunt failure in pediatric patients with hydrocephalus. This finding underscores the importance of considering the developmental stage at the time of surgery, rather than just prematurity status, when assessing shunt failure risk.

Surgical instruments and catheter damage during ventriculoperitoneal shunt assembly.

OBJECTIVE: Current surgical techniques use common surgical instruments for sterile shunt assembly. This study investigated the impact of using these techniques and surgical instruments on the mechanical integrity of the ventriculoperitoneal shunt system, specifically shunt catheters. METHODS: The authors conducted failure testing on 85 rifampin-coated catheters and 85 barium-impregnated catheters using 5 different surgical instruments and 2 different surgical techniques. In technique A, the distal end of the catheter was pushed onto the shunt valve inlet connector with the surgical instrument. In technique B, the catheter was pulled over the inlet connector. One hundred sixty catheters underwent 10-repetition-maximum testing, in which the catheter either failed before completion of 10 consecutive assembly/disassembly repetitions or the catheter completed 10 consecutive repetitions. The authors also conducted 100-repetition-maximum tests on 5 barium-impregnated and 5 rifampin-coated catheters using technique A. RESULTS: Catheter failure rates were significantly different among the different instruments used in assembly (p ≤ 0.001). Post hoc analysis showed that using mosquito forceps with shods resulted in a significantly lower catheter failure rate than the other instruments (p < 0.0005). The catheter failure rate of technique A was significantly lower than that of technique B (5% vs 81%, p < 0.001). There was no statistical difference between the failure rates of the barium and rifampin catheters (42% vs 44%, p = 0.9), but the barium catheters outperformed the rifampin catheters in the 100-repetition-maximum trials (p = 0.02). Instrument type (p = 0.0232) and catheter type (p = 0.0096) were both significant factors in determining the number of assembly/disassembly repetitions needed to cause catheter failure. It took an average of 2.79 repetitions of assembly/disassembly to cause catheter failure. DeBakey forceps had significantly lower mean repetitions to failure (mean 1.38) than the Gerald forceps without teeth (mean 2.73, p = 0.05) and bayonet (mean 3.25, p = 0.02). CONCLUSIONS: This study was the first of its kind to analyze how physical manipulation affects the mechanical integrity of ventriculoperitoneal shunt components. The authors demonstrated a significantly lower shunt catheter failure rate when mosquito forceps with shods and technique A were used in assembly. Moreover, the authors established that use of DeBakey forceps resulted in failure with fewer assembly/disassembly repetitions than use of the Gerald and bayonet forceps, suggesting that DeBakey forceps are the most damaging instrument.

Male fathead minnow transcriptomes and associated chemical analytes in the Milwaukee estuary system.

Contaminants of Emerging Concern (CECs) can be measured in waters across the United States, including the tributaries of the Great Lakes. The extent to which these contaminants affect gene expression in aquatic wildlife is unclear. This dataset presents the full hepatic transcriptomes of laboratory-reared fathead minnows (Pimephales promelas) caged at multiple sites within the Milwaukee Estuary Area of Concern and control sites. Following 4 days of in situ exposure, liver tissue was removed from males at each site for RNA extraction and sequencing, yielding a total of 116 samples from which libraries were prepared, pooled, and sequenced. For each exposure site, 179 chemical analytes were also assessed. These data were created with the intention of inviting research on possible transcriptomic changes observed in aquatic species exposed to CECs. Access to both full sequencing reads of animal samples as well as water contaminant data across multiple Great Lakes sites will allow others to explore the health of these ecosystems in support of the aims of the Great Lakes Restoration Initiative.

Integration of Adverse Outcome Pathways, Causal Networks and 'Omics to Support Chemical Hazard Assessment.

Several approaches have been used in an attempt to simplify and codify the events that lead to adverse effects of chemicals including systems biology, 'omics, in vitro assays and frameworks such as the Adverse Outcome Pathway (AOP). However, these approaches are generally not integrated despite their complementary nature. Here we propose to integrate toxicogenomics data, systems biology information and AOPs using causal biological networks to define Key Events in AOPs. We demonstrate this by developing a causal subnetwork of 28 nodes that represents the Key Event of regenerative proliferation - a critical event in AOPs for liver cancer. We then assessed the effects of three chemicals known to cause liver injury and cell proliferation (carbon tetrachloride, aflatoxin B1, thioacetamide) and two with no known cell proliferation effects (diazepam, simvastatin) on the subnetwork using rat liver gene expression data from the toxicogenomic database Open TG-GATEs. Cyclin D1 (Ccnd1), a gene both causally linked to and sufficient to infer regenerative proliferation activity, was overexpressed after exposures to carbon tetrachloride, aflatoxin B1 and thioacetamide, but not in exposures to diazepam and simvastatin. These results were consistent with known effects on rat livers and liver pathology of exposed rats. Using these approaches, we demonstrate that transcriptomics, AOPs and systems biology can be applied to examine the presence and progression of AOPs in order to better understand the hazards of chemical exposure.