Neurointensive care of traumatic brain injury in the elderly—age-specific secondary insult levels and optimal physiological levels to target need to be defined

Background Elderly patients with traumatic brain injury increase. Current targets and secondary insult definitions during neurointensive care (NIC) are mostly based on younger patients. The aim was therefore to study the occurrence of predefined secondary insults and the impact on outcome in different ages with particular focus on elderly. Methods Patients admitted to Uppsala 2008–2014 were included. Patient characteristics, NIC management, monitoring data, and outcome were analyzed. The percentage of monitoring time for ICP, CPP, MAP, and SBP above-/below-predefined thresholds was calculated. Results Five hundred seventy patients were included, 151 elderly ≥ 65 years and 419 younger 16–64 years. Age ≥ 65 had significantly higher percentage of CPP > 100, MAP > 120, and SBP > 180 and age 16–64 had higher percentage of ICP ≥ 20, CPP ≤ 60, and MAP ≤ 80. Age ≥ 65 contributed independently to the different secondary insult patterens. When patients in all ages were analyzed, low percentage of CPP > 100 and SBP > 180, respectively, was significant predictors of favorable outcome and high percentage of ICP ≥ 20, CPP > 100, SBP ≤ 100, and SBP > 180, respectively, was predictors of death. Analysis of age interaction showed that patients ≥ 65 differed and had a higher odds for favorable outcome with large proportion of good monitoring time with SBP > 180. Conclusions Elderly ≥ 65 have different patterns of secondary insults/physiological variables, which is independently associated to age. The finding that SBP > 180 increased the odds of favorable outcome in the elderly but decreased the odds in younger patients may indicate that blood pressure should be treated differently depending on age.

Densitometric analysis of brain computed tomography as a new prognostic factor in patients with acute subdural hematoma

OBJECTIVEAcute subdural hematoma (ASDH) is a major cause of mortality and morbidity after traumatic brain injury (TBI). Surgical evacuation is the mainstay of treatment in patients with altered neurological status or significant mass effect. Nevertheless, concerns regarding surgical indication still persist. Given that clinicians often make therapeutic decisions on the basis of their prognosis assessment, to accurately evaluate the prognosis is of great significance. Unfortunately, there is a lack of specific and reliable prognostic models. In addition, the interdependence of certain well-known predictive variables usually employed to guide surgical decision-making in ASDH has been proven. Because gray matter and white matter are highly susceptible to secondary insults during the early phase after TBI, the authors aimed to assess the extent of these secondary insults with a brain parenchyma densitometric quantitative CT analysis and to evaluate its prognostic capacity.METHODSThe authors performed a retrospective analysis among their prospectively collected cohort of patients with moderate to severe TBI. Patients with surgically evacuated, isolated, unilateral ASDH admitted between 2010 and 2017 were selected. Thirty-nine patients were included. For each patient, brain parenchyma density in Hounsfield units (HUs) was measured in 10 selected slices from the supratentorial region. In each slice, different regions of interest (ROIs), including and excluding the cortical parenchyma, were defined. The injured hemisphere, the contralateral hemisphere, and the absolute differences between them were analyzed. The outcome was evaluated using the Glasgow Outcome Scale–Extended at 1 year after TBI.RESULTSFifteen patients (38.5%) had a favorable outcome. Collected demographic, clinical, and radiographic data did not show significant differences between favorable and unfavorable outcomes. In contrast, the densitometric analysis demonstrated that greater absolute differences between both hemispheres were associated with poor outcome. These differences were detected along the supratentorial region, but were greater at the high convexity level. Moreover, these HU differences were far more marked at the cortical parenchyma. It was also detected that these differences were more prone to ischemic and/or edematous insults than to hyperemic changes. Age was significantly correlated with the side-to-side HU differences in patients with unfavorable outcome.CONCLUSIONSThe densitometric analysis is a promising prognostic tool in patients diagnosed with ASDH. The supplementary prognostic information provided by the densitometric analysis should be evaluated in future studies.

The Potential of Brain-Specific Blood Biomarkers for TBI Patient Management, Diagnosis, and Clinical Research

Rapid and continuous monitoring and analysis of biomarkers present in blood after TBI could serve as a reliable and useful tool to distinguish type of injury, predict secondary insults, and evaluate the efficacy of therapeutic interventions. The use of biomarkers in combination with current disease monitoring and management tools could improve management of TBI patients and improve clinical trials for TBI drug development. In this chapter, the authors discuss current clinical studies on brain-specific neuronal and glial biomarkers of TBI and their association with short- and long-term TBI outcome and secondary insults, as well the ability of biomarkers to distinguish type of injury and correlation with treatment.

Omphalocele and Beckwith-Wiedemann Syndrome

This chapter discusses omphalocele, which is a neonatal abdominal wall defect through which abdominal visceral content herniates. Although omphalocele is similar in gross appearance to gastroschisis, it is more frequently associated with chromosomal abnormalities such as trisomies 13, 15, 18, and 21, and syndromes such as Beckwith-Wiedemann, Rieger’s, and prune belly syndrome. It is also more frequently associated with anomalies in other organ systems. Management of infants with Beckwith-Wiedemann syndrome and omphalocele can be challenging due to the concurrent risk of difficult airway and aspiration. Associated comorbidities also need to be addressed to avoid secondary insults in the perioperative period.

Effect of molecular mechanisms mediating bevacizumab (BEV) and vanucizumab (VAN) on gastrointestinal perforation: Use of artificial neural networks for integrated data analysis.

e15108 Background: VAN is a novel bispecific mAb targeting VEGF & ANG-2. A randomized phase 2 study (McCAVE) investigating VAN & BEV, each combined with chemotherapy (mFOLFOX-6), in 1L metastatic colorectal cancer patients was completed. Reported gastrointestinal perforation (GIP) events (including GI fistula & abdominal abscess) in both arms (approx. 10%) exceeded those expected with BEV+CTx. The present work focused on identifying the explicit molecular pathways mediating VAN/BEV associated GIP. Methods: Clinical data from McCave (safety outcomes & gene expression profiling) was integrated with data from other clinical/preclinical VAN/BEV studies. Machine learning was applied to the dataset to computationally infer GIP mechanisms. The methodology was constrained by relevant biological & clinical knowledge. Literature reviews & database queries mapped 194 unique proteins to 8 biological processes previously hypothesized to play a role in GIP. Identified proteins guided construction of a GIP protein interaction network which was transformed into an artificial neural network and was fitted to the dataset to predict molecular pathways/biological processes most likely linking VEGF-A and/or ANG-2 inhibition to GIP. Results: VAN/BEV were predicted to enhance GIP risk via 4 out of 8 previously suggested biological effects: (i) reduced GI mucosal integrity; (ii) impaired wound healing; (iii) inhibition of angiogenesis (iv) increased thromboembolic risk. The specific proteins & associated interactions predicted to mediate these 4 effects were identified as solely VEGF-A inhibition driven. These effects may drive increased susceptibility to GIP triggered by secondary insults, e.g. preclinical ulcer & intramural lesion. Candidate GIP biomarkers for monitoring these effects were identified, e.g., aPTT, citrulline & I-FABP. Conclusions: The molecular pathways mediating GIP in VAN/BEV treated patients are likely driven by VEGF inhibition with no contribution from ANG-2 inhibition. It is proposed, that in addition to VAN/BEV, one or more secondary insults to the GI tract wall are required to drive perforation.