Long-term Impairment Research Articles

Functional connectivity in resting-state networks relates to short-term global cognitive functioning in cardiac arrest survivors.

Long-term cognitive impairment is common in cardiac arrest survivors. Screening to identify patients at risk is recommended. Functional magnetic resonance brain imaging (fMRI) holds potential to contribute to prediction of cognitive outcomes. In this study, we investigated the possible value of early changes in resting-state networks for predicting short and long-term cognitive functioning of cardiac arrest survivors. We performed a prospective multicenter cohort study in cardiac arrest survivors in three Dutch hospitals. Resting-state fMRI scans were acquired within a month after cardiac arrest. We primarily focused on functional connectivity within the default-mode network (DMN) and salience network (SN), and additionally explored functional connectivity in seven other networks. Cognitive outcome was measured using the Montreal Cognitive Assessment (MoCA) during hospital admission and at 3 and 12 months, and by neuropsychological examination (NPE) at 12 months. We tested mixed effects models to evaluate the value of connectivity within the networks for predicting global cognitive outcomes at the three time points, and long-term cognitive outcomes in the memory, attention, and executive functioning domains. We included 80 patients (age 60 ± 11 years, 72 (90%) male). MoCA scores increased significantly between hospital admission and 3 months (ΔMoCAhospital-3M = 2.89, p < 0.01), but not between 3 and 12 months (ΔMoCA3M-12M = 0.38, p = 0.52). Connectivity within the DMN, SN, and dorsal attention network (DAN) was positively related to global cognitive functioning during hospital admission (βDMN = 0.85, p = 0.03; βSN = 1.48, p < 0.01; βDAN = 0.96, p = 0.01), but not at 3 and 12 months. Network connectivity was also unrelated to long-term memory, attention, or executive functioning. Resting-state functional connectivity in the DMN, SN, and DAN measured in the first month after cardiac arrest is related to short-term global, but not long-term global or domain-specific cognitive performance of survivors. These results do not support the value of functional connectivity within these RSNs for prediction of long-term cognitive performance after cardiac arrest.

Chronic pain and use of painkillers, healthcare services and long-term impairment among Syrian refugees: a cross-sectional study

BackgroundThe global increase in forcibly displaced populations highlights the importance of understanding their health needs. Chronic pain is prevalent among refugees, poses significant personal and public health challenges, and complicates their integration into new home countries. Understanding refugees' pain post-migration and how it is being managed is crucial for ensuring adequate and timely interventions and fostering health equity. This paper explores the associations between pain levels and the use of painkillers, healthcare services, and long-term impairment among Syrian refugees with chronic pain, one year after their resettlement in Norway.MethodsThis cross-sectional study is based on survey data collected from 353 quota refugees in 2018–19, one year after resettlement in Norway. The primary outcomes were the use of painkillers, the use of healthcare services, and long-term impairment, according to reported chronic pain levels. Associations between these outcomes and chronic pain levels were studied using Poisson regression, adjusted by sociodemographic variables and trauma experience.ResultsOf the 353 adults included, 52% were women, and the median age was 36 years. A total of 5% reported very mild/mild, 10% moderate, and 12% strong/very strong chronic pain over the last four weeks. Significant associations were found between all chronic pain levels and use of non-prescription painkillers (adjusted relative risks (aRR) (95% CI)); mild (3.1 (2.0–4.7)), moderate (1.8 (1.1–2.8)), strong (1.7 (1.1–2.6)), and prescription painkillers; mild (4.6 (2.2–9.5)), moderate (5.6 (3.2–10.0)), strong (6.7 (3.9–11.3)), compared to those without chronic pain. Use of emergency rooms, specialist care, and hospitalization were significantly associated with strong chronic pain, with aRR (95% CI) of 2.0 (1.2–3.5), 3.9 (2.1–7.0) and 2.4 (1.3–4.4), respectively. Long-term impairment was strongly associated with chronic pain across all pain levels; mild (8.6 (5.6–13.49)), moderate (6.7 (4.3–10.5)) and strong (6.6 (4.3–10.4)).ConclusionDespite their young age, more than a quarter of the Syrian refugees in our study reported chronic pain one year after resettlement in Norway. High levels of pain were related to the use of medication, healthcare services, and long-term impairment. Understanding the dynamics of pain among refugees is crucial to ensure adequate and timely management.

Hyperspectral imaging of human liver allografts for prediction of initial graft function

PurposeIschemia reperfusion injury represents a significant yet difficult to assess risk factor for short- and long-term graft impairment in human liver transplantation (LT). As a non-invasive, non-ionizing tool, hyperspectral imaging (HSI) is capable of correlating optical properties with organ microperfusion. Hence, we here performed a study of human liver allografts assessed by HSI for microperfusion and prediction of initial graft function.MethodsImages of liver parenchyma of 37 human liver allografts were acquired at bench preparation, during normothermic machine perfusion (NMP), if applicable, and after reperfusion in the recipient. A specialized HSI acquisition software computed oxygen saturation (StO2), tissue hemoglobin indices (THI), near infrared perfusion indices (NIR), and tissue water indices (TWI). HSI parameters were analyzed for differences with regard to preservation technique, reperfusion sequence and presence of early allograft dysfunction (EAD).ResultsOrgan preservation was performed by means of NMP (n = 31) or static cold storage (SCS; n = 6). Patients’ demographics, donor characteristics, presence of EAD (NMP 36.7% vs. SCS 50%, p = 0.6582), and HSI parameters were comparable between both groups of preservation method. In organs developing EAD, NIR at 1, 2, and 4 h NMP and after reperfusion in the recipient was significantly lower (1 h NMP: 18.6 [8.6–27.6] vs. 28.3 [22.5–39.4], p = 0.0468; 2 h NMP: 19.4 [8.7–30.4] vs. 37.1 [27.5–44.6], p = 0.0011; 4 h NMP: 26.0 [6.8–37.1] vs. 40.3 [32.3–49.9], p = 0.0080; reperfusion: 13.0 [11.5–34.3] vs. 30.6 [19.3–44.0], p = 0.0212).ConclusionHSI assessment of human liver allografts is feasible during organ preservation and in the recipient. NIR during NMP and after reperfusion might predict the onset of EAD. Larger trials are warranted for assessment of this novel technique in human LT.

Early regional cerebral grey matter damage predicts long-term cognitive impairment phenotypes in multiple sclerosis: a 20-year study.

Despite grey matter atrophy in cortical and subcortical regions has been related to cognitive impairment in multiple sclerosis, only a few studies evaluated its predictive value for alterations in the long-term. We aimed to determine early predictors of cognitive status after 20 years of multiple sclerosis. In this longitudinal retrospective study, participants underwent a 1.5 T MRI scanning at diagnosis (T0) and after two years (T2), which included the evaluation of regional grey matter volume loss patterns. All individuals with multiple sclerosis underwent a comprehensive neuropsychological assessment at the end of the study and were classified considering their global and specific cognitive domains status (memory, attention/information processing speed, executive functioning). Clinical and MRI characteristics were assessed as predictors of long-term cognitive impairment. Analysis of covariance, t-test, unadjusted and adjusted (for age, sex, disease duration, volume of white matter lesions, volume of cortical lesions) logistic regression were conducted. One hundred seventy-five people with multiple sclerosis (118 females; mean ± SD age at the end of study = 47.7 ± 9.4 years) clinically followed for 20 years from onset (mean ± SD = 19.9 ± 5.1) were evaluated. At the end of the study, 81 (47%) were classified as cognitively impaired: 38 as mildly impaired (22%), and 43 as severely impaired (25%). In particular, 46 were impaired in memory (27%), 66 were impaired in attention/information processing speed (38%), and 71 were impaired in executive functioning (41%). Regression models identified precuneus (adjusted odds ratio = 3.37; P < 0.001), insula (adjusted odds ratio = 2.33; P = 0.036), parahippocampal gyrus (adjusted odds ratio = 2.07; P < 0.001) and cingulate (adjusted odds ratio = 1.81; P = 0.009) as the most associated regions with global cognitive impairment and domains-specific cognitive alterations after a mean of 20 years of multiple sclerosis, after adjusting for demographic and clinical variables as well as for focal white matter and grey matter damage. Early grey matter volume loss of specific cortical and deep grey matter regions predicts global and domain cognitive alterations after 20 years from multiple sclerosis diagnosis.

Primary vesicoureteral reflux.

Primary vesicoureteral reflux (VUR) is one of the most common urological abnormalities in infants and children. The association of VUR, urinary tract infection (UTI) and renal parenchymal damage is well established. The most serious complications of VUR-associated reflux nephropathy are hypertension and proteinuria with chronic kidney disease. Over the past two decades, our understanding of the natural history of VUR has improved, which has helped to identify patients at increased risk of both VUR and VUR-associated renal injury. The main goals in the treatment of paediatric patients with VUR are the prevention of recurrent UTIs and minimizing the risk of renal scarring and long-term renal impairment. Currently, there are four options for managing primary VUR in infants and children: surveillance or intermittent treatment of UTIs with management of bladder and bowel dysfunction; continuous antibiotic prophylaxis; endoscopic subureteral injection of tissue-augmenting substances; and ureteral reimplantation via open, laparoscopic or robotic-assisted surgery. Current debates regarding key aspects of management include when to perform diagnostic imaging and how to best identify the paediatric patients that will benefit from continuous antibiotic prophylaxis or surgical intervention, including endoscopic injection therapy and minimally invasive ureteral reimplantation. Evolving technologies, such as artificial intelligence, have the potential to assist clinicians in the decision-making process and in the individualization of diagnostic imaging and treatment of infants and children with VUR in the future.

TCD-Guided management in carotid endarterectomy: a retrospective study

BackgroundːStroke, primarily resulting from ischemic conditions, is the foremost cause of mortality and long-term impairment and is frequently associated with narrowing of the carotid arteries. Although carotid endarterectomy (CEA) is the treatment of choice, it carries the risk of cerebral ischemia and reduced blood flow. Transcranial Doppler (TCD) ultrasound offers a nonintrusive method to assess cerebral blood circulation during CEA, potentially enhancing surgical outcomes. The objective of this study was to assess the clinical utility and safety of TCD monitoring during CEA and to identify factors influencing postoperative complications.MethodsThis retrospective analysis included 158 CEA patients (from January 2021–August 2023) who underwent TCD monitoring and whose data were compared to historical standard care data. The primary outcomes were operation duration and artery occlusion time. Secondary outcomes included carotid shunt usage, seven-day postoperative complications, and six-month carotid artery patency. Logistic regression identified factors linked to adverse reactions, and a predictive model was evaluated with a receiver operating characteristic (ROC) curve.ResultsːComparative analysis indicated significant reductions in both the duration of surgery (113.26 ± 7.29 min) and artery occlusion time (21.85 ± 2.92 min) for patients monitored with TCD (P < 0.001) and an increase in carotid shunt implementation (25% as opposed to traditional care). The observed postoperative complications were minor, with a nonsignificant trend that favored the use of TCD-monitored procedures (1% vs. historical rates). Factors such as patient age and plaque echogenicity were found to be predictive of postoperative issues, with plaque echogenicity emerging as a significant predictive factor (OR = 10.70, 95% CI: 2.14–202, P = 0.02) upon multivariate analysis. The predictive model exhibited high precision (AUC = 0.93).ConclusionThis retrospective evaluation suggested that TCD monitoring in the CEA may reduce procedural time and potentially decrease postoperative complications, supporting its use for personalized surgical planning.

BL-918 alleviates oxidative stress in rats after subarachnoid hemorrhage by promoting mitophagy through the ULK1/PINK1/Parkin pathway

Background and purposeOxidative stress plays a critical role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). The small molecule ULK1 agonist, BL-918, demonstrated neuroprotective effects in other central nervous system diseases; however, its role in SAH has not yet been explored. This study aimed to evaluate whether BL-918 could provide neuroprotective effects in rats following SAH. MethodsAn SAH model was established in Sprague-Dawley rats using endovascular perforation. BL-918 was administered intraperitoneally after SAH, while the ULK1 inhibitor SBI was given intraperitoneally prior to SAH modeling. PINK1 siRNA was administered into the lateral ventricle before SAH induction. The neuroprotective effects and mechanisms of BL-918 were assessed through SAH grading, brain water content measurement, blood-brain barrier permeability, neurobehavioral tests, Western blot, immunofluorescence, TUNEL staining, DHE staining, and transmission electron microscopy (TEM). ResultsAfter SAH, the expression levels of p-ULK1, PINK1, Parkin, and LC3Ⅱ increased, peaking at 24 h post-SAH. BL-918 treatment improved neurological function in rats, reduced brain water content and blood-brain barrier permeability, and exhibited anti-oxidative stress and anti-apoptotic effects. Western blot analysis revealed that BL-918 increased the expression of p-ULK1, PINK1, Parkin, LC3Ⅱ, Bcl-xl, and Bcl-2 while inhibiting the expression of Bax and Cleaved Caspase-3. Oxidative stress-related indicators showed that BL-918 alleviated oxidative stress. Immunofluorescence and TEM results demonstrated that BL-918 promoted mitophagy and preserved mitochondrial morphology. Furthermore, the positive effects of BL-918 were reversed by SBI and PINK1 siRNA, respectively. ConclusionBL-918 improved both short-term and long-term neurological impairments in rats after SAH and reduced oxidative stress by promoting mitophagy, at least partially through the ULK1/PINK1/Parkin signaling pathway.

N-Pep-Zn Improves Cognitive Functions and Acute Stress Response Affected by Chronic Social Isolation in Aged Spontaneously Hypertensive Rats (SHRs).

Aging and chronic stress are regarded as the most important risk factors of cognitive decline. Aged spontaneously hypertensive rats (SHRs) represent a suitable model of age-related vascular brain diseases. The aim of this study was to explore the effects of chronic isolation stress in aging SHRs on their cognitive functions and response to acute stress, as well as the influence of the chronic oral intake of N-Pep-Zn, the Zn derivative of N-PEP-12. Nine-month-old SHRs were subjected to social isolation for 3 months (SHRiso group), and one group received N-pep-Zn orally (SHRisoP, 1.5 mg/100 g BW). SHRs housed in groups served as the control (SHRsoc). The behavioral study included the following tests: sucrose preference, open field, elevated plus maze, three-chamber sociability and social novelty and spatial learning and memory in a Barnes maze. Levels of corticosterone, glucose and proinflammatory cytokines in blood plasma as well as salivary amylase activity were measured. Restraint (60 min) was used to test acute stress response. Isolation negatively affected the SHRs learning and memory in the Barnes maze, while the treatment of isolated rats with N-Pep-Zn improved their long-term memory and working memory impairments, making the SHRisoP comparable to the SHRsoc group. Acute stress induced a decrease in the relative thymus weight in the SHRiso group (but not SHRsoc), whereas treatment with N-Pep-Zn prevented thymus involution. N-pep-Zn mitigated the increment in blood cortisol and glucose levels induced by acute stress. N-pep-Zn enhanced the adaptive capabilities towards chronic (isolation) and acute (immobilization) stress in aged SHRs and prevented cognitive disturbances induced by chronic isolation, probably affecting the hypothalamo-pituitary-adrenal, sympathetic, and immune systems.

A Systematic Search and Review of Registered Pharmacological Therapies Investigated to Improve Outcomes after a Stroke

Introduction: Stroke burden is largely due to long-term impairments requiring prolonged care and loss of productivity. We aim to identify and assess studies of different registered pharmacological therapies as treatments for improving post-stroke impairments and/or disabilities. Methods: In a systematic search and review (PROSPERO registration: CRD42022376973), studies of treatments that have been investigated as recovery-enhancing or recovery-promoting treatments in adult patients who had suffered a stroke will be searched for, screened, and reviewed based on the following: participants (P): adult humans, aged 18 years or older, diagnosed with stroke; interventions (I): registered or marketed pharmacological therapies that have been investigated as recovery-enhancing or recovery-promoting treatments in stroke; comparators (C): active or placebo or no comparator; outcomes (O): stroke-related neurological impairments and functional/disability assessments. Data will be extracted from included papers, including patient demographics, study methods, keystroke inclusion criteria, details of intervention and control, and the reported outcomes. Result: “The best available studies” based on study design, study size, and/or date of publication for different therapies and stroke subtypes will be selected and graded for level of evidence by consensus. Conclusion: There are conflicting study results of pharmacological interventions after an acute stroke to enhance recovery. This systematic search and review will identify the best evidence and knowledge gaps in the pharmacological treatment of post-stroke patients as well as guide clinical decision-making and planning of future studies.

Impact of levetiracetam and ethanol on memory, selected neurotransmitter levels, oxidative stress parameters, and essential elements in rats.

Ethanol disrupts brain activity and memory. There is evidence supporting the beneficial effect of levetiracetam on alcohol consumption. Therefore, the aim of the study was to examine whether levetiracetam has a protective activity against ethanol-induced memory impairment, alterations in selected neurotransmission activities, oxidative stress, and selected essential elements in rats. The rats were given levetiracetam (300mg/kg b.w. po) with ethanol for three weeks prior to behavioral tests. Spatial memory was tested using the Morris water maze, while recognition memory was evaluated using the Novel object recognition test. The GABA and glutamate concentration was determined in three rat brain regions (cerebellum, hippocampus, and cerebral cortex). Serum oxidative stress parameters and selected essential elements concentration (Cu, Mn, Zn, Fe, Mg) in the rat brain were analyzed. Levetiracetam administered with ethanol improved spatial memory, but did not affect abstinence-induced impairment. The drug also decreased ethanol-induced long-term recognition memory impairment. No alterations in glutamate levels were observed. GABA levels were elevated by levetiracetam in the cerebral cortex and by ethanol in the cerebellum. Ethanol increased catalase activity (CAT) and decreased superoxide dismutase activity (SOD) in the serum. Levetiracetam significantly increased the activity of SOD. Alcohol disrupted the levels of trace elements (Mn, Zn, Mg) in the rat brain. Additionally, levetiracetam alone increased Mg, Fe, and Cu concentrations while all animals receiving the drug also had significantly lower concentrations of Zn. Levetiracetam had differential effects against ethanol-induced impairments. These findings could have important implications for future levetiracetam treatment in patients.

Knee joint pathology and efferent pathway dysfunction: Mapping muscle inhibition from motor cortex to muscle force

BackgroundDysfunction in efferent pathways after knee pathology is tied to long-term impairments in quadriceps and hamstrings muscle performance, daily function, and health-related quality of life. Understanding the underlying etiology is crucial for effective treatment and prevention of poor outcomes, such as post-traumatic osteoarthritis or joint replacement. ObjectivesTo synthesize recent evidence of efferent pathway dysfunction (i.e., motor cortex, motor units) among individuals with knee pathology. DesignCommentary. MethodWe summarize the current literature investigating the motor cortex, corticospinal tract, and motoneuron pool in individuals with three common knee pathologies: anterior cruciate ligament (ACL) injury, anterior knee pain (AKP), and knee osteoarthritis (OA). To offer a complete perspective, we draw from studies applying a range of neuroimaging and neurophysiologic techniques. ResultsAdaptations within the motor cortices, corticospinal tract, and motoneuron pool are present in those with knee pathology and underline impairments in quadriceps and hamstrings muscle function. Each pathology has evidence of altered motor system excitability and reduced volitional muscle activation and force-generating capacity, but few impairments were common across ACL injury, AKP, and OA studies. These findings underscore the central role of the motor cortex and motor unit behavior in the long-term outcomes of individuals with knee pathology. ConclusionsAdaptations in the efferent pathways underlie persistent muscle dysfunction across three common knee pathologies. This review provides an overview of these changes and summarizes key findings from neurophysiology and neuroimaging studies, offering direction for future research and clinical application in the rehabilitation of joint injuries.

Deep brain stimulation mitigates memory deficits in a rodent model of traumatic brain injury

BackgroundTraumatic brain injury (TBI) is a major life-threatening event. In addition to neurological deficits, it can lead to long-term impairments in attention and memory. Deep brain stimulation (DBS) is an established therapy for movement disorders that has been recently investigated for memory improvement in various disorders. In models of TBI, stimulation delivered to different brain targets has been administered to rodents long after the injury with the objective of treating motor deficits, coordination and memory impairment. ObjectiveTo test the hypothesis that DBS administered soon after TBI may prevent the development of memory deficits and exert neuroprotective effects. MethodsMale rats were implanted with DBS electrodes in the anterior nucleus of the thalamus (ANT) one week prior to lateral fluid percussion injury (FPI). Immediately after TBI, animals received active or sham stimulation for 6 h. Four days later, they were assessed in a novel object/novel location recognition test (NOR/NLR) and a Barnes maze paradigm. After the experiments, hippocampal cells were counted. Separate groups of animals were sacrificed at different timepoints after TBI to measure cytokines and brain derived neurotrophic factor (BDNF). In a second set of experiments, TBI-exposed animals receiving active or sham stimulation were injected with the tropomyosin receptor kinase B (TrkB) antagonist ANA-12, followed by behavioural testing. ResultsRats exposed to TBI given DBS had an improvement in several variables of the Barnes maze, but no significant improvements in NOR/NLR compared to Sham DBS TBI animals or non-implanted controls. Animals receiving stimulation had a significant increase in BDNF levels, as well as in hippocampal cell counts in the hilus, CA3 and CA1 regions. DBS failed to normalize the increased levels of TNFα and the proinflammatory cytokine IL1β in the perilesional cortex and the hippocampus of the TBI-exposed animals. Pharmacological experiments revealed that ANA-12 administered alongside DBS did not counter the memory improvement observed in ANT stimulated animals. ConclusionsDBS delivered immediately after TBI mitigated memory deficits, increased the expression of BDNF and the number of hippocampal cells in rats. Mechanisms for these effects were not related to an anti-inflammatory effect or mediated via TrkB receptors.

Effect of Backward Walking Versus Forward Walking Training on Balance Among Children with Cerebral Palsy

Background: Cerebral palsy is characterized by long-term impairments in movement and posture that limit an individual’s ability to perform daily activities. Effective rehabilitation methods, such as forward and backward walking training, can improve balance and functional mobility in children with cerebral palsy.Objective: To compare the effects of backward walking training versus forward walking training on balance in children with cerebral palsy.Methods: A randomized clinical trial was conducted with 20 children aged 7-14 years, recruited from Children’s Hospital and Jinnah Hospital, Lahore. Participants were randomly divided into two groups: Group A (Forward Walking Training) and Group B (Backward Walking Training). Each group underwent training three times per week for 40 minutes over four weeks. Balance and mobility were assessed using the Time-Up-and-Go (TUG) test, Pediatric Balance Scale (PBS), and Figure-8 Walk Test (FW8T). Statistical analysis was performed using SPSS version 25, with Mann-Whitney U test used for between-group comparisons.Results: The backward walking group showed significant improvements in TUG (p = 0.03), PBS (p = 0.01), and FW8T (p = 0.01) compared to the forward walking group.Conclusion: Backward walking training showed superior improvements in balance and functional mobility compared to forward walking training in children with cerebral palsy.

Exploring the effectiveness of eHealth interventions in treating Post Intensive Care Syndrome (PICS) outcomes: a systematic review

BackgroundIt remains unclear how to optimise critical care rehabilitation to reduce the constellation of long-term physical, psychological and cognitive impairments known as Post Intensive Care Syndrome (PICS). Possible reasons for poor recovery include access to care and delayed treatment. eHealth could potentially aid in increasing access and providing consistent care remotely. Our review aimed to evaluate the effectiveness of eHealth interventions on PICS outcomes.MethodsStudies reporting eHealth interventions targeting Post Intensive Care Syndrome outcomes, published in Medline, CINAHL, PsycINFO, Embase, and Scopus from 30th January 2010 to 12th February 2024, were included in the review. Study eligibility was assessed by two reviewers with any disagreements discussed between them or resolved by a third reviewer. Study quality and risk of bias were assessed using the Mixed Method Appraisal Tool. Further to the identification of effective strategies, our review also aimed to clarify the timeline of recovery considered and the outcomes or domains targeted by the interventions.ResultsThirteen studies were included in our review. Study duration, eHealth intervention delivery format, and outcome measures varied considerably. No studies reported a theory of behavioural change and only one study was co-produced with patients or carers. Most studies were conducted in the early post-discharge phase (i.e., < 3 months) and had feasibility as a primary outcome. The cognitive domain was the least targeted and no intervention targeted all three domains. Interventions targeting the psychological domain suggest generally positive effects. However, results were underpowered and preliminary. Though all studies were concluded to be feasible, most studies did not assess acceptability. In studies that did assess acceptability, the main facilitators of acceptability were usability and perceived usefulness, and the main barrier was sensitivity to mental health and cognitive issues.ConclusionOur systematic review highlighted the promising contributions of eHealth with preliminary support for the feasibility of interventions in the early stages of post-critical care rehabilitation. Future research should focus on demonstrating effectiveness, acceptability, the cognitive domain, and multi-component interventions.

Neonatal encephalopathy: a systematic review of reported treatment outcomes

BackgroundNeonatal encephalopathy (NE) is a multi-organ condition potentially leading to death or long-term neurodisability. Therapeutic hypothermia is the standard treatment for NE; however, long-term impairments remain common. Studies of new...

Peroxiredoxin-5 alleviates early brain injury after subarachnoid hemorrhage by reducing oxidative stress

Background and purposeFollowing subarachnoid hemorrhage (SAH), excessive activation of oxidative stress and cell apoptosis plays a critical role in early brain injury (EBI). Peroxiredoxin-5 (Prdx5), predominantly expressed in neuronal mitochondria, acts as an antioxidant. However, the role of Prdx5 in EBI after SAH remains unclear. This study aims to elucidate the antioxidative stress and anti-apoptotic effects of Prdx5 in rats following SAH. MethodsIn this study, an SAH model was established in Sprague-Dawley rats using endovascular perforation. Recombinant Prdx5 (rPrdx5) was administered intranasally to upregulate Prdx5 expression after SAH in rats. Prdx5 small interfering RNA (Prdx5 siRNA) was administered prior to SAH modelling. The neuroprotective effects of Prdx5 were validated through SAH grading, brain water content, blood-brain barrier permeability, neurobehavioral tests, immunofluorescence, TUNEL staining, and Western blotting. ResultsThe expression levels of endogenous Prdx5 significantly decreased after SAH. Treatment with rPrdx5 improved both short-term and long-term behaviour in rats, reduced brain water content and blood-brain barrier permeability, and exhibited anti-oxidative stress and anti-apoptotic effects. Measurements of oxidative stress-related indicators, including MDA, SOD, GSH-Px and GSH/GSSG, confirmed that Prdx5 can alleviate oxidative stress in rats after SAH. Western blot analysis showed that rPrdx5 significantly increased the expression of Bcl-XL and Bcl-2 and reduced the expression of Bax and Cleaved Caspase-3, thereby exerting anti-apoptotic effects. Additionally, Prdx5 siRNA reversed the neuroprotective effects of rPrdx5, exacerbated neuronal damage and blood-brain barrier permeability, and increased levels of oxidative stress and apoptosis. ConclusionIn conclusion, our study demonstrated that specifically upregulating the expression of Prdx5 can reduce oxidative stress and apoptosis in rats after SAH, while also improving both short-term and long-term neurological impairments. Prdx5 is primarily expressed in the mitochondria of neuronal cells and is a crucial target for reducing ROS after SAH. rPrdx5 treatment may offer a promising therapeutic approach for clinical SAH patients.

Olfactory Bulb Volume and Asymmetry as Predictors of Executive Dysfunction in Adolescents with Congenital Heart Disease.

Common sequelae for patients with congenital heart disease (CHD) are neurodevelopmental disabilities including executive function, attention, and socio-emotional deficits. Although these are common diagnoses for patients with CHD, limited research has investigated the mechanistic underpinnings of these findings. Our previous research examined the association between abnormal respiratory ciliary motion and brain abnormalities in infants with CHD. Results suggested that abnormal ciliary motion correlated to a spectrum of subtle dysplasia, notably within the olfactory bulb (OB)1. Our current study investigates whether OB anomalies predict neurodevelopmental outcomes for pediatric patients with CHD. We hypothesize that adolescents with CHD who exhibit aberrant morphological measurements in the OB are more likely to suffer from executive functional deficits. A prospective, observational study of 54 CHD and 75 healthy subjects, ages 6-25 years old, was completed under the supervision of a senior pediatric neuroradiologist. T2 3D Space and T2 Blade 2MM MRI images were manually segmented to extract volumetric bilateral regions of the OB and cerebrospinal fluid (CSF) using ITK-SNAP. Imaging metrics were correlated to OB asymmetry, CSF to OB ratio, total CSF volume, total OB volume, and independent left and right CSF and OB volumes. Linear regression was used to evaluate MRI morphologic measurements with co-variates: CHD status, sex, MRI age, and segmenter. Executive function was determined by the Behavioral Rating Inventory of Executive Function (BRIEF) Parent Report and Delis-Kaplan Executive Function System (D-KEFS) for subjects ages 6-16. Cognition and olfactory function were measured with the NIH Toolbox Cognitive Battery and Odor Identification Test, respectively. No statistically significant results were reported between cohorts for asymmetry of OB, CSF to OB ratio, total CSF volume, total OB volume, nor between independent left and right CSF and OB volumes. Increased OB volume was associated with worse outcomes on the BRIEF Parent Report (p≤0.03). Asymmetry of OB predicted poorer executive functioning as reported by parents on the BRIEF (p≤0.05). Overall, the CHD cohort demonstrated worse scores on the BRIEF Parent Report compared to controls. Across groups, no significant association was reported for olfaction function measured by the NIH Toolbox Odor Identification Test on a limited subset of participants. As survival rates for CHD improve, there is an increased risk of long-term neurodevelopmental impairments. Our findings identify adolescents who are at risk for executive dysfunction, particularly those showing increased OB volume and/or asymmetry of the OB. This is particularly concerning for the CHD population with atypical OB morphology, who also exhibit significantly poorer outcomes on the BRIEF Parent Report and face a higher overall risk. Increased OB volume and OB asymmetry are olfactory-based biomarkers that may help identify at-risk CHD patients earlier, enabling more timely intervention and support.

Professionalizing Emergency Medical Service Response Time

Abstract Prompt responses by emergency medical services (EMSs) are crucial in delivering efficient prehospital emergency treatment. The prompt arrival of EMS is strongly correlated with improved patient outcomes and increased chances of survival. To reduce the occurrence of long-term impairment or illness, the majority of EMS companies follow globally acknowledged response time benchmarks. Internationally, EMSs strive to achieve a response time of 8 min or less for 90% of life-threatening incidents. This research examines many variables that influence EMS response times and their subsequent consequences on patient outcomes. The measurement of response time starts with receipt of a clinical complaint call and concludes upon the arrival of EMS at the site. Timely and effective reactions are essential for the survival of patients, particularly in urgent medical situations. In contrast, there are data indicating that longer reaction times are associated with increased death rates. Various obstacles might hinder prompt EMS responses, including geographical obstacles, unfavorable weather and traffic conditions, and patient-specific considerations such as the kind of injury or sickness, medical history, age, and gender. In addition, a lack of staff, including insufficient workers, poor training, and the absence of standardized, up-to-date technology that simplify care delivery, may also cause delays in response times. Due to the crucial importance of EMS response times in prehospital emergency treatment, it is essential for EMS systems to make every effort to meet their response time goals.

SARS-CoV-2 infection induces hyaluronan production in vitro and hyaluronan levels in COVID-19 patients relate to morbidity and long-term lung impairment: a prospective cohort study.

We previously demonstrated that the lungs of deceased COVID-19 patients were filled with a clear hydrogel consisting of hyaluronan (HA). In this translational study, we investigated the role of HA at all stages of COVID-19 disease to map the consequences of elevated HA on morbidity and identify the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced HA production. A reduced alveolar surface area was observed in the lungs of deceased COVID-19 patients compared to healthy controls, as visualized by a 3D rendering of lung morphology using light-sheet fluorescence microscopy. We confirmed the presence of HA in lung biopsies and found large quantities of proinflammatory fragmented HA. The association of systemic HA in blood plasma and disease severity was assessed in patients with mild (WHO Clinical Progression Scale, WHO-CPS, 1-5) and severe COVID-19 (WHO-CPS, 6-9) during the acute and convalescent phases and related to lung function. We found that systemic levels of HA were high during acute COVID-19 disease, remained elevated during convalescence, and were associated with a reduced diffusion capacity. In vitro 3D-lung models, differentiated from primary human bronchial epithelial cells, were used to study the effects of SARS-CoV-2 infection on HA metabolism, and transcriptomic analyses revealed a dysregulation of HA synthases and hyaluronidases, both contributing to increased HA in apical secretions. Furthermore, corticosteroid treatment reduced the inflammation and downregulated HA synthases. Our findings demonstrate that HA plays a role in COVID-19 morbidity and that sustained elevated HA concentrations may contribute to long-term respiratory impairment.IMPORTANCEThis study provides insights into the role of hyaluronan (HA) in the severity and long-term impact of COVID-19 on lung function. Through extensive morphological examination of lung tissues and a multicenter study, we identified that HA levels are significantly elevated in COVID-19 patients, correlating with a reduced lung diffusion capacity during convalescence. Using a 3D-lung model, we further uncovered how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection causes a dysregulated HA metabolism, leading to increased HA production. Our findings provide valuable insights into the pathogenesis of SARS-CoV-2 and suggest that targeting HA metabolism could offer new therapeutic avenues for managing COVID-19, particularly to prevent long-term lung impairment. Additionally, HA holds potential as a biomarker for predicting disease severity, which could guide personalized treatment strategies.

Novel extracorporeal treatment for severe neonatal jaundice: a mathematical modelling study of allo-hemodialysis

Severe Neonatal Jaundice (SNJ) causes long-term neurocognitive impairment, cerebral palsy, auditory neuropathy, deafness, or death. We developed a mathematical model for allo-hemodialysis as a potential blood purification method for the treatment of SNJ in term or near-term infants. With allo-hemodialysis (allo-HD), the neonate’s blood flows through hollow fibers of a miniature 0.075 m2 hemodialyzer, while the blood of a healthy adult (“buddy”) flows counter-currently through the dialysate compartment. We simulated the kinetics of unconjugated bilirubin in allo-hemodialysis with neonate blood flow rates of 12.5 and 15 mL/min (for a 2.5 kg and 3.5 kg neonate, respectively), and 30 mL/min for the buddy. Bilirubin production rates in neonate and buddy were set to 6 and 3 mg/kg/day, respectively. Buddy bilirubin conjugation rate was calculated to obtain normal steady-state bilirubin levels. Albumin levels were set to 1.1, 2.1, 3.1 g/dL for the neonate and 3.3 g/dL for the buddy. Model simulations suggest that a 6-h allo-hemodialysis session could reduce neonatal bilirubin levels by > 35% and that this modality would be particularly effective with low neonatal serum albumin levels. Due to the high bilirubin conjugation capacity of an adult’s healthy liver and the larger distribution volume, the buddy’s bilirubin level increases only transiently during allo-hemodialysis. Our modelling suggests that a single allo-hemodialysis session may lower neonatal unconjugated bilirubin levels effectively. If corroborated in ex-vivo, animal, and clinical studies, this bilirubin reduction could lower the risks associated with SNJ, especially kernicterus, and possibly avoiding the morbidity associated with exchange transfusions.