Contribution of genetic variants in the development of familial premature coronary artery disease in a cohort of cardiac patients.

Coronary artery disease (CAD), the most prevalent cardiovascular disease, is the leading cause of death worldwide. Heritable factors play a significant role in the pathogenesis of CAD. It has been proposed that approximately one-third of patients with CAD have a positive family history, and individuals with such history are at ~1.5-fold increased risk of CAD in their lifespans. Accordingly, the long-recognized familial clustering of CAD is a strong risk factor for this disease. Our study aimed to identify candidate genetic variants contributing to CAD by studying a cohort of 60 large Iranian families with at least two members in different generations afflicted with premature CAD (PCAD), defined as established disease at ≤45 years in men and ≤55 years in women. Exome sequencing was performed for a subset of the affected individuals, followed by prioritization and Sanger sequencing of candidate variants in all available family members. Subsequently, apparently healthy carriers of potential risk variants underwent coronary computed tomography angiography (CCTA), followed by co-segregation analysis of the combined data. Putative causal variants were identified in seven genes, ABCG8, CD36, CYP27A1, PIK3C2G, RASSF9, RYR2, and ZFYVE21, co-segregating with familial PCAD in seven unrelated families. Among these, PIK3C2G, RASSF9, and ZFYVE21 are novel candidate CAD susceptibility genes. Our findings indicate that rare variants in genes identified in this study are involved in CAD development.

Advances in development of biomarkers for brain damage and ischemia.

Acquired brain injury is an urgent situation that requires rapid diagnosis and treatment. Magnetic resonance imaging (MRI) and computed tomography (CT) are required for accurate diagnosis. However, these methods are costly and require substantial infrastructure and specialized staff. Circulatory biomarkers of acute brain injury may help in the management of patients with acute cerebrovascular events and prevent poor outcome and mortality. The purpose of this review is to provide an overview of the development of potential biomarkers of brain damage to increase diagnostic possibilities. For this purpose, we searched the PubMed database of studies on the diagnostic potential of brain injury biomarkers. We also accessed information from Clinicaltrials.gov to identify any clinical trials of biomarker measurements for the diagnosis of brain damage. In total, we present 41 proteins, enzymes and hormones that have been considered as biomarkers for brain injury, of which 20 have been studied in clinical trials. Several microRNAs have also emerged as potential clinical biomarkers for early diagnosis. Combining multiple biomarkers in a panel, along with other parameters, is yielding promising outcomes.

Myoclonus in patients with COVID-19: Findings of autoantibodies against brain structures in cerebrospinal fluid.

BACKGROUND AND PURPOSE: COVID-19 is associated with multiple neurological manifestations. The clinical presentation, trajectory, and treatment response for three cases of myoclonus during COVID-19 infection, with no previous neurological disease, are decsribed. METODS: Analysis of cerebrospinal fluid from the cases using indirect immunohistochemistry. RESULTS: Antibodies against rodent brain tissue, and similarities in staining patterns were observed, indicating the presence of antineuronal immunoglobulin G autoantibodies targeting astrocytes in the hippocampus. CONCLUSION: Our results demontrate cerebrospinal fluid antineuronal antibodies indicating an an autoimmune involvment in the pathogenesis in COVID-19 associated myoclonus.

The management of severe traumatic brain injury in the initial postinjury hours - current evidence and controversies.

PURPOSE OF REVIEW: To provide an overview of recent studies discussing novel strategies, controversies, and challenges in the management of severe traumatic brain injury (sTBI) in the initial postinjury hours. RECENT FINDINGS: Prehospital management of sTBI should adhere to Advanced Trauma Life Support (ATLS) principles. Maintaining oxygen saturation and blood pressure within target ranges on-scene by anesthetist, emergency physician or trained paramedics has resulted in improved outcomes. Emergency department (ED) management prioritizes airway control, stable blood pressure, spinal immobilization, and correction of impaired coagulation. Noninvasive techniques such as optic nerve sheath diameter measurement, pupillometry, and transcranial Doppler may aid in detecting intracranial hypertension. Osmotherapy and hyperventilation are effective as temporary measures to reduce intracranial pressure (ICP). Emergent computed tomography (CT) findings guide surgical interventions such as decompressive craniectomy, or evacuation of mass lesions. There are no neuroprotective drugs with proven clinical benefit, and steroids and hypothermia cannot be recommended due to adverse effects in randomized controlled trials. SUMMARY: Advancement of the prehospital and ED care that include stabilization of physiological parameters, rapid correction of impaired coagulation, noninvasive techniques to identify raised ICP, emergent surgical evacuation of mass lesions and/or decompressive craniectomy, and temporary measures to counteract increased ICP play pivotal roles in the initial management of sTBI. Individualized approaches considering the underlying pathology are crucial for accurate outcome prediction.

Mild Traumatic Brain Injury in the Maturing Brain: An Investigation of Symptoms and Cognitive Performance in Soldiers Returning From Afghanistan and Iraq.

OBJECTIVE: The majority of traumatic brain injuries (TBIs) are classified as mild and occur in young individuals. The course of recovery varies but can result in chronic or troubling outcomes. The impact of age on TBI outcomes in young adults before complete brain maturation is not well studied. METHODS: In this study, we compared the effects of mild TBI on cognitive performance and self-reported TBI symptoms and posttraumatic stress disorder (PTSD) in 903 soldiers in 3 different age groups: 24 years or younger, 25 to 27 years, and 28 to 40 years. The soldiers had returned from war zones in Iraq and were screened for TBI within a few days of return. Cognitive performance was measured with the Automated Neuropsychological Assessment Metrics of Military TBI Version 4 (ANAM4). Symptoms associated with mild TBI were self-reported on the Neurobehavioral Symptom Inventory, and the PTSD Checklist-Civilian Version (PCL-C). RESULTS: Soldiers with TBI in every age group had significantly higher prevalence of most symptoms than those with no TBI. Soldiers with TBI also reported more chronic pain sites, regardless of age. Soldiers aged 28 to 40 years with TBI had the lowest cognitive performance scores (ANAM) across several subtests, both unadjusted and adjusted. The Global Deficit Score was significantly higher for soldiers aged 28 to 40 years and 25 to 27 years with TBI than for soldiers younger than 24 years with no TBI. After adjusting for PTSD symptoms, education, and number of lifetime TBIs, the overall test battery mean for soldiers aged 28 to 40 years with TBI was significantly lower than for soldiers younger than 24 years with no TBI. CONCLUSION: Soldiers with mild TBI in the younger age group show more symptoms associated to frontal lobe function while soldiers in the older group suffer more cognitive impairment. This may warrant further study as it may indicate a propensity to later cognitive decline among soldiers who were older at the time of injury.

Higher intracranial pressure variability is associated with lower cerebrovascular resistance in aneurysmal subarachnoid hemorrhage.

Higher intracranial pressure variability (ICPV) has been associated with a more favorable cerebral energy metabolism, lower rate of delayed ischemic neurologic deficits, and more favorable outcome in aneurysmal subarachnoid hemorrhage (aSAH). We have hypothesized that higher ICPV partly reflects more compliant and active cerebral vessels. In this study, the aim was to further test this by investigating if higher ICPV was associated with lower cerebrovascular resistance (CVR) and higher cerebral blood flow (CBF) after aSAH. In this observational study, 147 aSAH patients were included, all of whom had been treated in the Neurointensive Care (NIC) Unit, Uppsala, Sweden, 2012-2020. They were required to have had ICP monitoring and at least one xenon-enhanced computed tomography (Xe-CT) scan to study cortical CBF within the first 2 weeks post-ictus. CVR was defined as the cerebral perfusion pressure in association with the Xe-CT scan divided by the concurrent CBF. ICPV was defined over three intervals: subminute (ICPV-1m), 30-min (ICPV-30m), and 4 h (ICPV-4h). The first 14 days were divided into early (days 1-3) and vasospasm phase (days 4-14). In the vasospasm phase, but not in the early phase, higher ICPV-4h (ß = - 0.19, p < 0.05) was independently associated with a lower CVR in a multiple linear regression analysis and with a higher global cortical CBF (r = 0.19, p < 0.05) in a univariate analysis. ICPV-1m and ICPV-30m were not associated with CVR or CBF in any phase. This study corroborates the hypothesis that higher ICPV, at least in the 4-h interval, is favorable and may reflect more compliant and possibly more active cerebral vessels.

Preparation of pH-sensitive composite polyethersulfone membranes embedded by Ag(I) coordination polymer for the removal of cationic and anionic dyes.

A pH-sensitive polyethersulfone (PES) membrane was prepared with the aid of newly synthesized Ag(I) coordination polymer (Ag(I)-CP) particles. Indicating obvious adsorptive property toward dyes, the Ag(I)-based metalorganic framework (MOF) was selected to be used as an additive to improve the dye selectivity of PES membranes for both cationic and anionic dyes. The performance examination and characterization of prepared membranes indicated the influence of Ag(I)-CP in PES membrane improvement. The effect of feed pH approved the membrane response to pH changes in dye removal results. By adjusting feed pH based on pHpzc of Ag(I)-CP, it is possible to remove both anionic and cationic dyes (97% of acid orange 7 (AO) & and 100% of methylene blue (MB)) from the effluent along with an enhanced permeated flux. The results offered a synergism in embedding Ag(I)-CP in PES membrane in dye removal efficiency. The additive particles can be applied with their natural size (200-300 nm) without severe influence on the uniformity of the membrane morphology if the optimum Ag(I)-CP content is considered.

Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms.

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.

Protein Expression Profile of ACE2 in the Normal and COVID-19-Affected Human Brain.

SARS-coronavirus 2 (SARS-CoV-2) that caused the coronavirus disease 2019 (COVID-19) pandemic has posed to be a global challenge. An increasing number of neurological symptoms have been linked to the COVID-19 disease, but the underlying mechanisms of such symptoms and which patients could be at risk are not yet established. The suggested key receptor for host cell entry is angiotensin I converting enzyme 2 (ACE2). Previous studies on limited tissue material have shown no or low protein expression of ACE2 in the normal brain. Here, we used stringently validated antibodies and immunohistochemistry to examine the protein expression of ACE2 in all major regions of the normal brain. The expression pattern was compared with the COVID-19-affected brain of patients with a varying degree of neurological symptoms. In the normal brain, the expression was restricted to the choroid plexus and ependymal cells with no expression in any other brain cell types. Interestingly, in the COVID-19-affected brain, an upregulation of ACE2 was observed in endothelial cells of certain patients, most prominently in the white matter and with the highest expression observed in the patient with the most severe neurological symptoms. The data shows differential expression of ACE2 in the diseased brain and highlights the need to further study the role of endothelial cells in COVID-19 disease in relation to neurological symptoms.

Prognosis in moderate-severe traumatic brain injury in a Swedish cohort and external validation of the IMPACT models.

BACKGROUND: A major challenge in management of traumatic brain injury (TBI) is to assess the heterogeneity of TBI pathology and outcome prediction. A reliable outcome prediction would have both great value for the healthcare provider, but also for the patients and their relatives. A well-known prediction model is the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) prognostic calculator. The aim of this study was to externally validate all three modules of the IMPACT calculator on TBI patients admitted to Uppsala University hospital (UUH). METHOD: TBI patients admitted to UUH are continuously enrolled into the Uppsala neurointensive care unit (NICU) TBI Uppsala Clinical Research (UCR) quality register. The register contains both clinical and demographic data, radiological evaluations, and outcome assessments based on the extended Glasgow outcome scale extended (GOSE) performed at 6 months to 1 year. In this study, we included 635 patients with severe TBI admitted during 2008-2020. We used IMPACT core parameters: age, motor score, and pupillary reaction. RESULTS: The patients had a median age of 56 (range 18-93), 142 female and 478 male. Using the IMPACT Core model to predict outcome resulted in an AUC of 0.85 for mortality and 0.79 for unfavorable outcome. The CT module did not increase AUC for mortality and slightly decreased AUC for unfavorable outcome to 0.78. However, the lab module increased AUC for mortality to 0.89 but slightly decreased for unfavorable outcome to 0.76. Comparing the predicted risk to actual outcomes, we found that all three models correctly predicted low risk of mortality in the surviving group of GOSE 2-8. However, it produced a greater variance of predicted risk in the GOSE 1 group, denoting general underprediction of risk. Regarding unfavorable outcome, all models once again underestimated the risk in the GOSE 3-4 groups, but correctly predicts low risk in GOSE 5-8. CONCLUSIONS: The results of our study are in line with previous findings from centers with modern TBI care using the IMPACT model, in that the model provides adequate prediction for mortality and unfavorable outcome. However, it should be noted that the prediction is limited to 6 months outcome and not longer time interval.

Cerebral Blood Flow and Oxygen Delivery in Aneurysmal Subarachnoid Hemorrhage: Relation to Neurointensive Care Targets.

BACKGROUND: The primary aim was to determine to what extent continuously monitored neurointensive care unit (neuro-ICU) targets predict cerebral blood flow (CBF) and delivery of oxygen (CDO2) after aneurysmal subarachnoid hemorrhage. The secondary aim was to determine whether CBF and CDO2 were associated with clinical outcome. METHODS: In this observational study, patients with aneurysmal subarachnoid hemorrhage treated at the neuro-ICU in Uppsala, Sweden, from 2012 to 2020 with at least one xenon-enhanced computed tomography (Xe-CT) obtained within the first 14 days post ictus were included. CBF was measured with the Xe-CT and CDO2 was calculated based on CBF and arterial oxygen content. Regional cerebral hypoperfusion was defined as CBF < 20 mL/100 g/min, and poor CDO2 was defined as CDO2 < 3.8 mL O2/100 g/min. Neuro-ICU variables including intracranial pressure (ICP), pressure reactivity index, cerebral perfusion pressure (CPP), optimal CPP, and body temperature were assessed in association with the Xe-CT. The acute phase was divided into early phase (day 1-3) and vasospasm phase (day 4-14). RESULTS: Of 148 patients, 27 had underwent a Xe-CT only in the early phase, 74 only in the vasospasm phase, and 47 patients in both phases. The patients exhibited cerebral hypoperfusion and poor CDO2 for medians of 15% and 30%, respectively, of the cortical brain areas in each patient. In multiple regressions, higher body temperature was associated with higher CBF and CDO2 in the early phase. In a similar regression for the vasospasm phase, younger age and longer pulse transit time (lower peripheral resistance) correlated with higher CBF and CDO2, whereas lower hematocrit only correlated with higher CBF but not with CDO2. ICP, CPP, and pressure reactivity index exhibited no independent association with CBF and CDO2. R2 of these regressions were below 0.3. Lower CBF and CDO2 in the early phase correlated with poor outcome, but this only held true for CDO2 in multiple regressions. CONCLUSIONS: Systemic and cerebral physiological variables exhibited a modest association with CBF and CDO2. Still, cerebral hypoperfusion and low CDO2 were common and low CDO2 was associated with poor outcome. Xe-CT imaging could be useful to help detect secondary brain injury not evident by high ICP and low CPP.

The extent of neuroradiological findings in COVID-19 shows correlation with blood biomarkers, Glasgow coma scale score and days in intensive care.

BACKGROUND AND PURPOSE: A wide range of neuroradiological findings has been reported in patients with coronavirus disease 2019 (COVID-19), ranging from subcortical white matter changes to infarcts, haemorrhages and focal contrast media enhancement. These have been descriptively but inconsistently reported and correlations with clinical findings and biomarkers have been difficult to extract from the literature. The purpose of this study was to quantify the extents of neuroradiological findings in a cohort of patients with COVID-19 and neurological symptoms, and to investigate correlations with clinical findings, duration of intensive care and biomarkers in blood. MATERIAL AND METHODS: Patients with positive SARS-CoV-2 and at least one new-onset neurological symptom were included from April until July 2020. Nineteen patients were examined regarding clinical symptoms, biomarkers in blood and MRI of the brain. In order to quantify the MRI findings, a semi-quantitative neuroradiological severity scale was constructed a priori, and applied to the MR images by two specialists in neuroradiology. RESULTS AND CONCLUSIONS: The score from the severity scale correlated significantly with blood biomarkers of CNS injury (glial fibrillary acidic protein, total-tau, ubiquitin carboxyl-terminal hydrolase L1) and inflammation (C-reactive protein), Glasgow Coma Scale score, and the number of days spent in intensive care. The underlying radiological assessments had inter-rater agreements of 90.5%/86% (for assessments with 2/3 alternatives). Total intraclass correlation was 0.80. Previously reported neuroradiological findings in COVID-19 have been diverse and heterogenous. In this study, the extent of findings in MRI examination of the brain, quantified using a structured report, shows correlation with relevant biomarkers.

Biomarkers for central nervous system injury in cerebrospinal fluid are elevated in COVID-19 and associated with neurological symptoms and disease severity.

BACKGROUND AND PURPOSE: Neurological symptoms have been frequently reported in hospitalized patients with coronavirus disease 2019 (COVID-19), and biomarkers of central nervous system (CNS) injury are reported to be increased in plasma but not extensively studied in cerebrospinal fluid (CSF). This study examined CSF for biomarkers of CNS injury and other pathology in relation to neurological symptoms and disease severity in patients with neurological manifestations of COVID-19. METHODS: Nineteen patients with neurological symptoms and mild to critical COVID-19 were prospectively included. Extensive analysis of CSF, including measurement of biomarkers of CNS injury (neurofilament light chain [NfL] protein, glial fibrillary acidic protein [GFAp], and total tau), was performed and compared to neurological features and disease severity. RESULTS: Neurological symptoms included altered mental status (42%), headache (42%), and central (21%) and peripheral weakness (32%). Two patients demonstrated minor pleocytosis, and four patients had increased immunoglobulin G levels in CSF. Neuronal autoantibody testing using commercial tests was negative in all patients. Increased CSF levels of NfL protein, total tau, and GFAp were seen in 63%, 37%, and 16% of patients, respectively. Increased NfL protein correlated with disease severity, time in intensive care, and level of consciousness. NfL protein in CSF was higher in patients with central neurological symptoms. CONCLUSIONS: Although limited by the small sample size, our data suggest that levels of NfL protein, GFAp, and total tau in CSF are commonly elevated in patients with COVID-19 with neurological symptoms. This is in contrast to the standard CSF workup where pathological findings are scarce. NfL protein, in particular, is associated with central neurological symptoms and disease severity.

Arterial Oxygenation in Traumatic Brain Injury-Relation to Cerebral Energy Metabolism, Autoregulation, and Clinical Outcome.

BACKGROUND: Ischemic and hypoxic secondary brain insults are common and detrimental in traumatic brain injury (TBI). Treatment aims to maintain an adequate cerebral blood flow with sufficient arterial oxygen content. It has been suggested that arterial hyperoxia may be beneficial to the injured brain to compensate for cerebral ischemia, overcome diffusion barriers, and improve mitochondrial function. In this study, we investigated the relation between arterial oxygen levels and cerebral energy metabolism, pressure autoregulation, and clinical outcome. METHODS: This retrospective study was based on 115 patients with severe TBI treated in the neurointensive care unit, Uppsala university hospital, Sweden, 2008 to 2018. Data from cerebral microdialysis (MD), arterial blood gases, hemodynamics, and intracranial pressure were analyzed the first 10 days post-injury. The first day post-injury was studied in particular. RESULTS: Arterial oxygen levels were higher and with greater variability on the first day post-injury, whereas it was more stable the following 9 days. Normal-to-high mean pO2 was significantly associated with better pressure autoregulation/lower pressure reactivity index (P = .02) and lower cerebral MD-lactate (P = .04) on day 1. Patients with limited cerebral energy metabolic substrate supply (MD-pyruvate below 120 µM) and metabolic disturbances with MD-lactate-/pyruvate ratio (LPR) above 25 had significantly lower arterial oxygen levels than those with limited MD-pyruvate supply and normal MD-LPR (P = .001) this day. Arterial oxygenation was not associated with clinical outcome. CONCLUSIONS: Maintaining a pO2 above 12 kPa and higher may improve oxidative cerebral energy metabolism and pressure autoregulation, particularly in cases of limited energy substrate supply in the early phase of TBI. Evaluating the cerebral energy metabolic profile could yield a better patient selection for hyperoxic treatment in future trials.

Acute disseminated encephalomyelitis with delayed onset and feasibility of the Miethke shunt and sensor reservoir system: a case report.

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating central nervous system disorder with predilection for early childhood. Delayed onset of ADEM is rare, and herein we present a previously healthy 5-year-old boy, with an unusual clinical course of ADEM with high intracranial pressure (ICP) and acute visual loss that was at first diagnosed as idiopathic intracranial hypertension without papilledema (IIHWOP). The boy underwent acute neurosurgical intervention with ventriculoperitoneal (VP) shunt using Miethke valve and sensor reservoir system and received high-dose steroid treatment with symptom relieve within days. This is the first case report using this system in such a young child, and we find it feasible and valuable also in younger children when VP shunt with ICP measurement is indicated.

The Role of BDNF in Experimental and Clinical Traumatic Brain Injury.

Traumatic brain injury is one of the leading causes of mortality and morbidity in the world with no current pharmacological treatment. The role of BDNF in neural repair and regeneration is well established and has also been the focus of TBI research. Here, we review experimental animal models assessing BDNF expression following injury as well as clinical studies in humans including the role of BDNF polymorphism in TBI. There is a large heterogeneity in experimental setups and hence the results with different regional and temporal changes in BDNF expression. Several studies have also assessed different interventions to affect the BDNF expression following injury. Clinical studies highlight the importance of BDNF polymorphism in the outcome and indicate a protective role of BDNF polymorphism following injury. Considering the possibility of affecting the BDNF pathway with available substances, we discuss future studies using transgenic mice as well as iPSC in order to understand the underlying mechanism of BDNF polymorphism in TBI and develop a possible pharmacological treatment.

Histopathology of Parasellar Neoplasms.

The anatomical and histological complexity of the parasellar region as well as the presence of embryonic remnants determine the huge diversity of parasellar neoplasms. Some of them are only located in the parasellar region, whereas others can occur elsewhere, within or outside the central nervous system. Their spectrum ranges from histologically benign and low-grade malignant to high-grade malignant tumours. Although rare, metastases can pose differential diagnostic dilemmas. The severity of the clinical picture, the challenges of surgery and the risk of adverse sequelae related to surgery or radiotherapy make parasellar tumours interesting entities for the clinicians irrespective of their histological malignancy grade. Due to the different cell origins of parasellar tumours, the World Health Organization classification system does not categorise them as a distinct group. Detailed criteria for classification and malignancy grading are presented in the classification systems covering central nervous system tumours, haematological malignancies and tumours of the soft tissue and bone. In the last few years, molecular genetic features have been integrated into the diagnosis of several types of the parasellar tumours enhancing diagnostic accuracy and providing information of the value for targeting therapies. In this review, we will present histopathological and molecular genetic features, updated classification criteria and recent advances in the diagnostics and rationale for novel pharmacological therapies of selected types of parasellar neoplasms.

Temporal Dynamics of Cerebral Blood Flow During the Acute Course of Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT.

BACKGROUND: Compromised cerebral blood flow (CBF) is a crucial factor in delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Repeated measurement of CBF may improve our understanding of the temporal dynamics following SAH. The aim of this study was to assess CBF at different phases of the acute course in poor-grade SAH patients, hypothesizing more pronounced disturbances at day 4-7, and that the initial level of CBF determines the following course of CBF. METHODS: Mechanically ventilated SAH patients were scheduled for bedside measurement of regional and global cortical CBF at day 0-3, 4-7, and 8-12, using xenon-enhanced computed tomography in a mobile setup. Patients were dichotomized depending on high or low initial global cortical CBF and cutoff level 30 ml/100 g/min. RESULTS: Eighty-one patients were included, and 51 had measurements at day 0-3 and 4-7. In patients with high initial CBF, the level was unchanged at day 4-7; 37.7 (IQR 32.6-46.7) ml/100 g/min versus 36.8 (IQR 29.5-44.8). The low-CBF group showed a slight increase from 23.6 (IQR 21.0-28.1) ml/100 g/min to 28.4 (IQR 22.7-38.3) (P = 0.025), still markedly lower than the high-CBF group (P = 0.016). In the low-CBF group, CBF increased in patients who received hypertension, hypervolemia, and hemodilution (HHH therapy) but remained low in standard treated patients. For the subset of 27 patients examined also at day 8-12, the differences depending on initial CBF level were no longer statistically significant. Among patients with still low CBF at day 4-7, the proportion who had poor short-term outcome was 55% compared to 35% (n.s.) for patients with high CBF. CONCLUSIONS: CBF studied in poor-grade SAH patients at large did not show any statistically significant changes over time. Stratifying patients by high or low initial CBF and whether HHH therapy was given revealed an association between low initial CBF and persistent low CBF at day 4-7. These findings may be of clinical relevance in managing SAH patients with low early CBF.

High Arterial Glucose is Associated with Poor Pressure Autoregulation, High Cerebral Lactate/Pyruvate Ratio and Poor Outcome Following Traumatic Brain Injury.

BACKGROUND: Arterial hyperglycemia is associated with poor outcome in traumatic brain injury (TBI), but the pathophysiology is not completely understood. Previous preclinical and clinical studies have indicated that arterial glucose worsens pressure autoregulation. The aim of this study was to evaluate the relationship of arterial glucose to both pressure reactivity and cerebral energy metabolism. METHOD: This retrospective study was based on 120 patients with severe TBI treated at the Uppsala University hospital, Sweden, 2008-2018. Data from cerebral microdialysis (glucose, pyruvate, and lactate), arterial glucose, and pressure reactivity index (PRx55-15) were analyzed the first 3 days post-injury. RESULTS: High arterial glucose was associated with poor outcome/Glasgow Outcome Scale-Extended at 6-month follow-up (r = - 0.201, p value = 0.004) and showed a positive correlation with both PRx55-15 (r = 0.308, p = 0.001) and cerebral lactate/pyruvate ratio (LPR) days 1-3 (r = 0. 244, p = 0.014). Cerebral lactate-to-pyruvate ratio and PRx55-15 had a positive association day 2 (r = 0.219, p = 0.048). Multivariate linear regression analysis showed that high arterial glucose predicted poor pressure autoregulation on days 1 and 2. CONCLUSIONS: High arterial glucose was associated with poor outcome, poor pressure autoregulation, and cerebral energy metabolic disturbances. The latter two suggest a pathophysiological mechanism for the negative effect of arterial hyperglycemia, although further studies are needed to elucidate if the correlations are causal or confounded by other factors.

Alterations of the human gut Methanobrevibacter smithii as a biomarker for inflammatory bowel diseases.

It is hypothesized that direct and indirect homeostasis between gut microbiota plays a key role in different intestine disorders. Archaea methanogens, an ancient domain of single-celled organism, are major archaea in the digestive system. Recent evidence has shown that the variable prevalence of methanogens in different individuals could have certain effects on inflammatory bowel diseases (IBD). We aimed to assess the prevalence of Methanobrevibacter smithii between Iranian patients suffering from IBD and healthy control subjects. Stool DNA extracts from 47 healthy controls and 61 IBD patients were investigated. Quantitative real time PCR was performed for detecting Mbb. smithii load. We found a significantly decreased the Mbb. smithii load between IBD patients and healthy subjects. It is assumed that there is a reverse association between Mbb. smithii bacterial load and susceptibility to IBD, and this association could be extended to IBD patients in remission as we found that Mbb. smithii bacterial load is markedly higher among healthy subjects in comparison to IBD patients.