Exploratory factor analysis yields grouping of brain injury biomarkers significantly associated with outcomes in neonatal and pediatric ECMO.

In this two-center prospective cohort study of children on ECMO, we assessed a panel of plasma brain injury biomarkers using exploratory factor analysis (EFA) to evaluate their interplay and association with outcomes. Biomarker concentrations were measured daily for the first 3 days of ECMO support in 95 participants. Unfavorable composite outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category > 2 with decline ≥ 1 point from baseline. EFA grouped 11 biomarkers into three factors. Factor 1 comprised markers of cellular brain injury (NSE, BDNF, GFAP, S100ß, MCP1, VILIP-1, neurogranin); Factor 2 comprised markers related to vascular processes (vWF, PDGFRß, NPTX1); and Factor 3 comprised the BDNF/MMP-9 cellular pathway. Multivariable logistic models demonstrated that higher Factor 1 and 2 scores were associated with higher odds of unfavorable outcome (adjusted OR 2.88 [1.61, 5.66] and 1.89 [1.12, 3.43], respectively). Conversely, higher Factor 3 scores were associated with lower odds of unfavorable outcome (adjusted OR 0.54 [0.31, 0.88]), which is biologically plausible given the role of BDNF in neuroplasticity. Application of EFA on plasma brain injury biomarkers in children on ECMO yielded grouping of biomarkers into three factors that were significantly associated with unfavorable outcome, suggesting future potential as prognostic instruments.

Brain injury plasma biomarkers in patients on veno-arterial extracorporeal membrane oxygenation: A pilot prospective observational study.

INTRODUCTION: Early diagnosis of acute brain injury (ABI) is critical for patients on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) to guide anticoagulation strategy; however, neurological assessment in ECMO is often limited by patient sedation. METHODS: In this pilot study of adults from June 2018 to May 2019, plasma samples of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and tubulin associated unit (Tau) were collected daily after V-A ECMO cannulation and measured using a multiplex platform. Primary outcomes were occurrence of ABI, assessed clinically, and neurologic outcome, assessed by modified Rankin Scale (mRS). RESULTS: Of 20 consented patients (median age = 48.5°years; 55% female), 8 (40%) had ABI and 15 (75%) had unfavorable neurologic outcome at discharge. 10 (50%) patients were centrally cannulated. Median duration on ECMO was 4.5°days (IQR: 2.5-9.5). Peak GFAP, NFL, and Tau levels were higher in patients with ABI vs. without (AUC = 0.77; 0.85; 0.57, respectively) and in patients with unfavorable vs. favorable neurologic outcomes (AUC = 0.64; 0.59; 0.73, respectively). GFAP elevated first, NFL elevated to the highest degree, and Tau showed limited change regardless of ABI. CONCLUSION: Further studies are warranted to determine how plasma biomarkers may facilitate early detection of ABIs in V-A ECMO to assist timely clinical decision-making.

Predicting Academic Productivity Among American Shoulder and Elbow Surgeons (ASES) Fellowship Faculty from Publications Acquired Before and During Surgical Training.

BACKGROUND: Orthopedic residency and fellowship applicants with a strong research record are highly valued for their potential in continuing academic excellence. Despite this, the association between research productivity during training and future academic productivity as an attending orthopedic surgeon is not well-established. We assess the effects of research output during different periods of surgical training as well as residency location on long-term academic productivity as an attending shoulder and elbow surgeon. METHODS: A search of the 2022-2023 American Shoulder and Elbow Surgeons (ASES) Fellowship Directory was conducted to identify a list of orthopedic shoulder and elbow fellowship faculty members. Each surgeon's residency, fellowship and current institution of practice were determined and stratified by geographic location. Total publication counts acquired before residency, during residency, during fellowship, and after fellowship were collected for each faculty member. Attending publication rates and H-indices were calculated. A multivariate linear regression model was created, and significance was set at a P-value < 0.05. RESULTS: A total of 149 shoulder and elbow fellowship faculty members representing 34 fellowship programs were identified. The average number of total publications per surgeon was 88.8 ± 102. The average attending publication rate was 5.29 ± 6.89 publications per year. The average H-index for included surgeons was 27.8 ± 24.4. The number of publications acquired before residency (ß = 0.293; P < 0.001), during residency (ß = 0.110; P = 0.025) and during fellowship (ß = 0.593; P < 0.001) were significantly associated with an increased attending publication rate, but no association was observed with the H-index [before residency (ß = -0.221; P = 0.574), during residency (ß = 0.045; P = 0.866), during fellowship (ß = 0.198; P = 0.678)]. There were no significant differences in total publication count (P = 0.397), attending publication rate (P = 0.237), or H-index (P = 0.364) based on location of residency training. DISCUSSION: Research output before and during surgical training is predictive of continued academic productivity as a shoulder and elbow surgeon. In particular, greater productivity during surgical fellowship was most predictive of academic output as an attending. While long-term academic productivity does not seem to be influenced by the geographic location of residency training, attending surgeons practicing in the Midwest had significantly greater total publication counts and H-indices but similar annual publication rates. LEVEL OF EVIDENCE: Survey Study; Cross Sectional Design; Literature and Internet Sources.

A review of emerging membrane-based microalgal-bacterial processes for wastewater treatment: Process configurations, biological and membrane performance, and perspectives.

Microalgal-bacterial (MB) consortia create an excellent eco-system for simultaneous COD/BOD and nutrients (N and P) removals in a single step with significant reduction in or complete elimination of aeration and carbonation in the biological wastewater treatment processes. The integration of membrane separation technology with the MB processes has created a new paradigm for research and development. This paper focuses on a comprehensive and critical literature review of recent advances in these emerging processes. Novel membrane process configurations and process conditions affecting the biological performance of these novel systems have been systematically reviewed and discussed. Membrane fouling issues and control of MB biofilm formation and thickness associated with these emerging suspended growth or immobilized biofilm processes are addressed and discussed. The research gaps, challenges, outlooks of these emerging processes are identified and discussed in-depth. The findings from the literature suggest that the membrane-based MB processes are advanced biotechnologies with a significant reduction in energy consumption and process simplification and high process efficiency that are not achievable with current technologies in wastewater treatment. There are endless opportunities for research and development of these novel and emerging membrane-based MB processes.

A Light Touch: Solar Photocatalysis Detoxifies Oil Sands Process-Affected Waters Prior to Significant Treatment of Naphthenic Acids.

Environmental reclamation of Canada's oil sands tailings ponds is among the single largest water treatment challenges globally. The toxicity of oil sands process-affected water (OSPW) has been associated with its dissolved organics, a complex mixture of naphthenic acid fraction components (NAFCs). Here, we evaluated solar treatment with buoyant photocatalysts (BPCs) as a passive advanced oxidation process (P-AOP) for OSPW remediation. Photocatalysis fully degraded naphthenic acids (NAs) and acid extractable organics (AEO) in 3 different OSPW samples. However, classical NAs and AEO, traditionally considered among the principal toxicants in OSPW, were not correlated with OSPW toxicity herein. Instead, nontarget petroleomic analysis revealed that low-polarity organosulfur compounds, composing <10% of the total AEO, apparently accounted for the majority of waters' toxicity to fish, as described by a model of tissue partitioning. These findings have implications for OSPW release, for which a less extensive but more selective treatment may be required than previously expected.

Bailout Distal Internal Carotid Artery Stenting after Carotid Endarterectomy: Indications, Technique, and Outcomes.

BACKGROUND: Distal internal carotid artery (ICA) stenting may be employed as a bailout maneuver when an inadequate end point or clamp injury is encountered at the time of carotid endarterectomy (CEA) in a surgically inaccessible region of the distal ICA. We sought to characterize the indications, technique, and outcomes for this infrequently encountered clinical scenario. METHODS: We performed a retrospective review of all patients who underwent distal ICA stenting at the time of CEA at our institution between September 2008 and July 2022. Procedural details and postoperative follow-up were reviewed for each patient. RESULTS: Six patients were identified during the study period. All were male with an age range of 63 to 82 years. Five underwent carotid revascularization for asymptomatic carotid artery stenosis, and one patient was treated for amaurosis fugax. Three patients were on dual antiplatelet therapy preoperatively, whereas 2 were on aspirin monotherapy, and one was on aspirin and low-dose rivaroxaban. Five patients underwent CEA with patch angioplasty, and one underwent eversion CEA. The indication for stenting was distal ICA dissection due to clamp or shunt injury in 2 patients and an inadequate distal ICA end point in 4 patients. In all cases, access for stenting was obtained under direct visualization within the common carotid artery, and a standard carotid stent was deployed with its proximal aspect landing within the endarterectomized site. Embolic protection was typically achieved via proximal common carotid artery and external carotid artery clamping for flow arrest with aspiration of debris before restoration of antegrade flow. There was 100% technical success. Postoperatively, 2 patients were found to have a cranial nerve injury, likely occurring due to the need for high ICA exposure. Median length of stay was 2 days (range 1-7 days) with no instances of perioperative stroke or myocardial infarction. All patients were discharged on dual antiplatelet therapy with no further occurrence of stroke, carotid restenosis, or reintervention through a median follow-up of 17 months. CONCLUSIONS: Distal ICA stenting is a useful adjunct in the setting of CEA complicated by inadequate end point or vessel dissection in a surgically inaccessible region of the ICA and can minimize the need for high-risk extensive distal dissection of the ICA in this situation.

A type 4 resistant potato starch alters the cecal microbiome and gene expression in mice fed a western diet based on NHANES data.

Four major types of resistant starch (RS1-4) are present in foods, all of which can alter the microbiome and are fermented in the cecum and colon to produce short-chain fatty acids (SCFAs). Type 4 RSs are chemically modified starches, not normally found in foods, but have become a popular food additive as their addition increases fiber content. Multiple studies, in humans and rodents, have explored how different RS4 affect post-prandial glucose metabolism, but fewer studies have examined the effects of RS4 consumption on the microbiome. In addition, many RS studies conducted in rodents use high-fat diets that do not approximate what is typically consumed by humans. To address this, mice were fed a Total Western Diet (TWD), based on National Health and Nutrition Examination Survey (NHANES) data that mimics the macro and micronutrient composition of a typical American diet, for six weeks, and then supplemented with 0, 2, 5, or 10% of the RS4, Versafibe 1490™ (VF), a phosphorylated and cross-linked potato starch, for an additional three weeks. The cecal contents were analyzed for SCFA content and microbiota composition. Butyrate production was increased while branched chain SCFA production decreased. The alpha-diversity of the microbiome decreased in mice fed the TWD with 10% VF 1490 added while the beta-diversity plot showed that the 5% and 10% VF groups were distinct from mice fed the TWD. Similarly, the largest changes in relative abundance of various genera were greatest in mice fed the 10% VF diet. To examine the effect of VF consumption on tissue gene expression, cecal and distal colon tissue mRNA abundance were analyzed by RNASeq. Gene expression changes were more prevalent in the cecum than the colon and in mice fed the 10% VF diet, but the number of changes was substantially lower than we previously observed in mice fed the TWD supplemented with native potato starch (RPS). These results provide additional evidence that the structure of the RS is a major factor determining its effects on the microbiome and gene expression in the cecum and colon.

Application of the Geriatric Trauma Outcome Score in a Rural Setting.

OBJECTIVE: To retrospectively apply the Geriatric Trauma Outcome (GTO) score to the patient population of a rural South Central Appalachian level 1 trauma center and identify the potential utility of the GTO score in guiding goals of care discussions. METHODS: Trauma registry data was extracted for 5,627 patients aged 65+ from 2017 to 2021. GTO score was calculated for each patient. Descriptive statistics were calculated for age, Injury Severity Score (ISS), GTO score, receipt of red blood cells, discharge status, and code status. A simple logistic regression model was used to determine the relationship between GTO score and discharge status. The probability of mortality was then calculated using GTO score, and the distribution of code status among patients with ≤50, 51-75%, and >75% probability of mortality was examined. RESULTS: For every 10-point increase in GTO score, odds of mortality increased by 79% (OR = 1.79; P < .001). Patients had an estimated 50% probability of mortality with a GTO score of 156, 75% with 174, and 99% with a score of 234, respectively. Seventeen patients had a GTO score associated with >75% probability of mortality. Of those 17 patients, four retained a full code status. CONCLUSIONS: Our analysis demonstrates that the GTO score is a validated measure in a rural setting and can be an easily calculated metric to help determine a geriatric patient's probability of mortality following a trauma. The results of our study also found that GTO score can be used to inform goals of care discussions with patients.

Outcome of Seatbelt Education and Safety Program Among Teenagers.

Despite the effectiveness of seatbelts, concerns persist about compliance, especially among teenagers. Survey data from a local high school and registry data from a level 1 trauma center were used to observe seatbelt and motor vehicle accident trends. The survey data was analyzed to gauge student's sentiments on seatbelt education. The trauma center data was analyzed to identify characteristics and trends among teenage motor vehicle accidents. Social media was the most common strategy selected for seatbelt safety awareness. Random seatbelt checks performed over 4 months revealed seatbelt compliance rates of 90%, 93.55%, and 96.94% after education intervention. Trauma center data showed that lack of seatbelt usage resulted in greater morbidity. These findings emphasize the need for targeted interventions. This study provides insights into creating effective education campaigns that can be used to enhance safety belt compliance and potentially reduce injury.

Roles of pH and phosphate in rare earth element biosorption with living acidophilic microalgae.

The increasing demand for rare earth elements (REEs) has spurred interest in the development of recovery methods from aqueous waste streams. Acidophilic microalgae have gained attention for REE biosorption as they can withstand high concentrations of transition metals and do not require added organic carbon to grow, potentially allowing simultaneous sorption and self-replication of the sorbent. Here, we assessed the potential of Galdieria sulphuraria for REE biosorption under acidic, nutrient-replete conditions from solutions containing ≤ 15 ppm REEs. Sorption at pH 1.5-2.5 (the growth optimum of G. sulphuraria) was poor but improved up to 24-fold at pH 5.0 in phosphate-free conditions. Metabolic activity had a negative impact on REE sorption, additionally challenging the feasibility of REE biosorption under ideal growth conditions for acidophiles. We further examined the possibility of REE biosorption in the presence of phosphate for biomass growth at elevated pH (pH ≥ 2.5) by assessing aqueous La concentrations in various culture media. Three days after adding La into the media, dissolved La concentrations were up to three orders of magnitude higher than solubility predictions due to supersaturation, though LaPO4 precipitation occurred under all conditions when seed was added. We concluded that biosorption should occur separately from biomass growth to avoid REE phosphate precipitation. Furthermore, we demonstrated the importance of proper control experiments in biosorption studies to assess potential interactions between REEs and matrix ions such as phosphates. KEY POINTS: • REE biosorption with G. sulphuraria increases significantly when raising pH to 5 • Phosphate for biosorbent growth has to be supplied separately from biosorption • Biosorption studies have to assess potential matrix effects on REE behavior.

Higher levels of brain injury biomarker tau are associated with unfavorable outcomes in patients supported with ECMO following cardiac arrest.

Aim: We sought to determine if higher plasma levels of brain injury biomarkers neurofilament light (NfL), phosphorylated tau 181 (pT181), tau, and ubiquitin C-terminal hydrolase L1 (UCHL1) were associated with unfavorable outcomes in children supported on extracorporeal membrane oxygenation (ECMO) with and without preceding cardiac arrest. Methods: We conducted a secondary analysis of a two-center prospective observational study of ECMO patients 0-<18 years. Plasma concentrations of NfL, pT181, tau, and UCHL1 were measured on ECMO days 1, 2 and 3. Unfavorable outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category (PCPC) >2 with decline from baseline PCPC among survivors. Results: Among 88 children on ECMO, mean tau levels were significantly higher on each of the first three ECMO days in children who underwent extracorporeal cardiopulmonary resuscitation (ECPR) compared to those with non-ECPR cardiac arrest or with no cardiac arrest preceding ECMO. Higher ECMO day 1 tau levels were significantly associated with increased hazard of unfavorable outcome in unadjusted (HR, 1.35, 95% CI 1.09-1.66) and adjusted (HR, 1.42; 95% CI 1.13-1.79) models. Higher levels of NfL or pT181 were not associated with increased hazard for unfavorable outcome in multivariable models. UCHL1 values were outside of detectable limits and thus deferred from analysis. Conclusions: Levels of tau were significantly associated with increased hazard of death or unfavorable neurologic outcome in unadjusted and adjusted models. Biomarkers of brain injury, particularly tau, may aid in detection of neurologic injury and neuroprognostication in patients on ECMO with and without preceding cardiac arrest.

The Rising Quality of Randomized Controlled Trials in The Journal of Bone & Joint Surgery: An Updated Analysis from 2014 to 2022.

Background: Previous reports found that 40% of randomized controlled trials (RCTs) published in The Journal of Bone & Joint Surgery (JBJS) from 1988 to 2000 and 47% of those published from 2001 to 2013 were of high quality. The purpose of this study was to assess the quality of RCTs published from 2014 to 2022 in JBJS and to compare these findings with those of prior analyses in order to identify trends over time and areas for continued improvement. Methods: PubMed was searched for the term "randomized controlled trial" to identify studies published in JBJS from 2014 to 2022. Each included RCT was evaluated with use of the Detsky score and a risk-of-bias assessment modified from the Cochrane tool. These evaluations were then compared with previous evaluations of RCTs from the 1988 to 2000 and 2001 to 2013 periods with use of independent-sample t tests. A transformed Detsky score of >75% and a modified risk-of-bias score of ≥8 were defined as being indicative of high quality. Results: A total of 218 RCTs were published in JBJS from 2014 to 2022. An a priori sample size was calculated in 183 studies (83.9%). A total of 152 (83.1%) of the 183 studies enrolled the calculated number of patients, of which 126 (82.9%) maintained an adequate number at the time of final follow-up. Most RCTs were conducted at a single center (146 of 218; 67%), evaluated a surgical intervention (162 of 218; 74%), and reported positive results (142 of 218; 65%). The mean transformed Detsky score was 85% ± 10% (95% confidence interval, 83.7% to 86.3%), with 82% of trials (179 of 218) scored as high quality. The mean transformed Detsky score from 2014 to 2022 was higher than that from 1988 to 2000 and that from 2001 to 2013 (85% versus 76% and 68%, respectively; p < 0.001). The mean modified risk-of-bias score was 7 ± 1, with 42% of trials (92 of 218) scored as high quality. RCTs published from 2014 to 2022 had a higher mean modified risk-of-bias score than those published from 2001 to 2013 (7 ± 1 versus 6 ± 1; p < 0.001). Compared with the 2001 to 2013 and 2014 to 2022 periods, the 1988 to 2000 period had a greater proportion of trials that reported positive results (51% and 65% versus 82%, respectively; p < 0.001) and that included data from multiple centers (31% and 33% versus 67%; p < 0.001). Conclusions: The quality of RCTs published in JBJS from 2014 to 2022 has improved from that reported previously, as demonstrated by the increases in the modified risk-of-bias score and transformed Detsky score from prior periods. This may be the result of journal policies such as the requirements of CONSORT adherence and prospective trial registration. Investigators should focus on improving the clarity of reporting, limiting attrition bias, and making efforts to blind support staff in order to increase the quality of future RCTs. Clinical Relevance: Improving the quality of RCTs is crucial given their potential to influence current clinical practice.

Orthopedic surgeon-scientist representation is low among National Institutes of Health grants for rotator cuff research.

Background: The purpose of this study is to characterize National Institutes of Health (NIH) funding for rotator cuff research and evaluate the impact of orthopedic surgeons on this portfolio. Methods: The NIH's Research Portfolio Online Reporting Tools Expenditures and Results database was queried for "rotator cuff repair" or "rotator cuff tear" from the 2011 to 2021 fiscal years. Compound annual growth rates were calculated and grants were categorized by basic, clinical, or translational research. Funding totals were compared by Principal Investigator (PI) and grant characteristics. Results: A total of 52 grants were awarded to 38 PIs between 2011 and 2021, totaling $40,156,859. Annual NIH funding for rotator cuff tear and rotator cuff repair increased by a Compound annual growth rate of 11.0% from 2011 to 2021, compared to 3.4% for the total NIH budget. Orthopedic surgeon-scientists received $9,208,212 (22.9%), most commonly through R01 (80.5%) and K08 (7.1%) mechanisms. No significant difference in funding was found by PI sex (P = .332), degree (P = .460), academic rank (P = .118), or researcher type (P = .227). Professors had a higher h-index than associate and assistant professors (P = .001). Orthopedic surgeon-scientists had a higher h-index (mean 36.3 ± 9.4) compared to clinician-scientists (mean 8.0 ± 1.4) and research-scientists (35.5 ± 40.7) (P = .044). Clinical topics receiving the highest funding were rehabilitation (23.9%), diagnosis, (22.3%) and surgical technique (14.8%). Orthopedic surgeon-scientists acquired funding for diagnosis (57.1%), rehabilitation (17.0%), and surgical technique (14.5%). Discussion: While NIH funding for rotator cuff research is growing, orthopedic surgeon representation is low. Future studies should evaluate barriers to obtaining funding for orthopedic surgeon-scientists.

Phospholipid-rich krill oil promotes intestinal health by strengthening beneficial gut microbial interactions in an infectious colitis model.

Krill oil (KO) is rich in bioactive ingredients including phospholipids, omega-3 fatty acids, and astaxanthin. While health benefits and roles of KO in modulating lipid metabolism are well documented, its ability to alleviate symptoms related to infectious colitis and modulate gut microbial interactions is still largely unknown. Here we used a multi-omics approach, including transcriptome, microbiome, and metabolome analyses, to understand how KO mediates gut microbial interactions and promotes epithelial healing in an infectious colitis model. KO reversed the infection-induced intestinal hyperplasia to baseline. KO dampened intestinal inflammation via multiple targets, mediating several proinflammatory pathways, including IL17 signaling, and reducing luminal histamine levels. KO supplementation enriched butyrate-producing bacteria, including Roseburia and Clostridium, and strengthened beneficial microbial interactions in the gut microbial community. Supplementation with phospholipid-rich KO also increased microbial phylogenetic diversity. KO enhanced mucosal barrier function by increasing the production of Muc6 and the antimicrobial peptide, Leap2. KO played an active role during epithelial healing by inhibiting the expression of granzyme K while increasing the expression of a colitis protective factor, Dclk1. Together, our findings demonstrate that KO rich in omega-3 phospholipids can play a protective role in infectious colitis and should be considered a dietary option for promoting gut health.

The impact of COVID-19 vaccine reactions on secondary vaccine hesitancy.

BACKGROUND: Primary and booster vaccinations are critical for mitigating COVID-19 transmission, morbidity, and mortality. Future booster vaccine campaigns rely on an increased understanding of vaccine hesitancy. OBJECTIVE: To evaluate self-reported allergic and skin vaccine reactions as factors potentially associated with vaccine hesitancy in a nationwide vaccine allergy registry. METHODS: Responses to survey questions concerning COVID-19 vaccine perceptions, coded from free text by 2 independent reviewers. Multivariable logistic regression models were used to determine the association between changed negative perception and respondent demographics, vaccination history, and reaction characteristics. RESULTS: A total of 993 individuals (median of 46 years [IQR, 36-59], 88% female, 82% White) self-reported reactions to COVID-19 vaccination. Reactions included the following: delayed large local skin reaction (40%), hives/urticaria (32%), immediate large local skin reaction (3%), swelling (3%), anaphylaxis (2%), and other or unspecified (20%). Most respondents were initially unconcerned about the safety of COVID-19 vaccines (56%). After reactions, 401 of 993 (40%) report negative change in perception of vaccination, with more than half of these respondents (n = 211, 53%) citing their reasoning as a negative experience with adverse effects. Of 102 individuals asked about future vaccination, 79 (77%) indicated that they were unlikely or very unlikely to receive future COVID-19 vaccinations. Increased negative perception after reaction was associated with younger age, later COVID-19 vaccination dose number, and reaction type. CONCLUSION: Our findings reveal that an individual's experience with allergic or cutaneous adverse effects after COVID-19 vaccination affects attitudes and decision-making regarding future vaccination, even in initially non-hesitant individuals. Further investigation of secondary vaccine hesitancy is necessary for adapting public health messaging to this important population.

Quantification of Diffusion Magnetic Resonance Imaging for Prognostic Prediction of Neonatal Hypoxic-Ischemic Encephalopathy.

Neonatal hypoxic-ischemic encephalopathy (HIE) is the leading cause of acquired neonatal brain injury with the risk of developing serious neurological sequelae and death. An accurate and robust prediction of short- and long-term outcomes may provide clinicians and families with fundamental evidence for their decision-making, the design of treatment strategies, and the discussion of developmental intervention plans after discharge. Diffusion tensor imaging (DTI) is one of the most powerful neuroimaging tools with which to predict the prognosis of neonatal HIE by providing microscopic features that cannot be assessed by conventional magnetic resonance imaging (MRI). DTI provides various scalar measures that represent the properties of the tissue, such as fractional anisotropy (FA) and mean diffusivity (MD). Since the characteristics of the diffusion of water molecules represented by these measures are affected by the microscopic cellular and extracellular environment, such as the orientation of structural components and cell density, they are often used to study the normal developmental trajectory of the brain and as indicators of various tissue damage, including HIE-related pathologies, such as cytotoxic edema, vascular edema, inflammation, cell death, and Wallerian degeneration. Previous studies have demonstrated widespread alteration in DTI measurements in severe cases of HIE and more localized changes in neonates with mild-to-moderate HIE. In an attempt to establish cutoff values to predict the occurrence of neurological sequelae, MD and FA measurements in the corpus callosum, thalamus, basal ganglia, corticospinal tract, and frontal white matter have proven to have an excellent ability to predict severe neurological outcomes. In addition, a recent study has suggested that a data-driven, unbiased approach using machine learning techniques on features obtained from whole-brain image quantification may accurately predict the prognosis of HIE, including for mild-to-moderate cases. Further efforts are needed to overcome current challenges, such as MRI infrastructure, diffusion modeling methods, and data harmonization for clinical application. In addition, external validation of predictive models is essential for clinical application of DTI to prognostication.

Evaluating Injury Severity in Neonatal Encephalopathy Using Automated Quantitative Electroencephalography Analysis: A Pilot Study.

Quantitative analysis of electroencephalography (qEEG) is a potential source of biomarkers for neonatal encephalopathy (NE). However, prior studies using qEEG in NE were limited in their generalizability due to individualized techniques for calculating qEEG features or labor-intensive pre-selection of EEG data. We piloted a fully automated method using commercially available software to calculate the suppression ratio (SR), absolute delta power, and relative delta, theta, alpha, and beta power from EEG of neonates undergoing 72 h of therapeutic hypothermia (TH) for NE between April 20, 2018, and November 4, 2019. We investigated the association of qEEG with degree of encephalopathy (modified Sarnat score), severity of neuroimaging abnormalities following TH (National Institutes of Child Health and Development Neonatal Research Network [NICHD-NRN] score), and presence of seizures. Thirty out of 38 patients met inclusion criteria. A more severe modified Sarnat score was associated with higher SR during all phases of TH, lower absolute delta power during all phases except rewarming, and lower relative delta power during the last 24 h of TH. In 21 patients with neuroimaging data, a worse NICHD-NRN score was associated with higher SR, lower absolute delta power, and higher relative beta power during all phases. QEEG features were not significantly associated with the presence of seizures after correction for multiple comparisons. Our results are consistent with those of prior studies using qEEG in NE and support automated qEEG analysis as an accessible, generalizable method for generating biomarkers of NE and response to TH. Additionally, we found evidence of an immature relative frequency composition in neonates with more severe brain injury, suggesting that automated qEEG analysis may have a use in the assessment of brain maturity.