Unique aspects of IFN-γ/STAT1 signaling in neurons.

The IFN-γ/STAT1 immune signaling pathway impacts many homeostatic and pathological aspects of neurons, beyond its canonical role in controlling intracellular pathogens. Well known for its potent pro-inflammatory and anti-viral functions in the periphery, the IFN-γ/STAT1 pathway is rapidly activated then deactivated to prevent excessive inflammation; however, neurons utilize unique IFN-γ/STAT1 activation patterns, which may contribute to the non-canonical neuron-specific downstream effects. Though it is now well-established that the immune system interacts and supports the CNS in health and disease, many aspects regarding IFN-γ production in the CNS and how neurons respond to IFN-γ are unclear. Additionally, it is not well understood how the diversity of the IFN-γ/STAT1 pathway is regulated in neurons to control homeostatic functions, support immune surveillance, and prevent pathologies. In this review, we discuss the neuron-specific mechanisms and kinetics of IFN-γ/STAT1 activation, the potential sources and entry sites of IFN-γ in the CNS, and the diverse set of homeostatic and pathological effects IFN-γ/STAT1 signaling in neurons has on CNS health and disease. We will also highlight the different contexts and conditions under which IFN-γ-induced STAT1 activation has been studied in neurons, and how various factors might contribute to the vast array of downstream effects observed.

Cerebrospinal fluid viral escape in HIV patients on antiretroviral therapy: A systematic review of reported cases.

Cerebrospinal fluid (CSF) viral escape rarely occurs when HIV is detected in the CSF, while it is undetectable in the blood plasma or detectable in CSF at levels that exceed those in the blood plasma. We conducted this review to comprehensively synthesise its clinical presentation, diagnosis, management strategies and treatment outcomes. A review registered with PROSPERO (CRD42023475311) searched evidence across PubMed/MEDLINE, Embase, Web of Science, Scopus, and Google Scholar to gather articles (case reports/series) that report on CSF viral escape in people living with HIV (PLHIV) on antiretroviral therapy (ART). The quality of studies was assessed based on the domains of selection, ascertainment, causality, and reporting. A systematic search identified 493 articles and 27 studies that include 21 case reports, and six case series were involved in the review. The studies reported 62 cases of CSF viral escape in PLHIV. The majority were men (66.67%), with a median age of 43 (range: 28-73) years. Approximately, 31 distinct symptoms were documented, mostly being cognitive dysfunction, gait abnormalities, and tremors (12.51%). Diagnosis involved blood and CSF analysis, magnetic resonance imaging, and neuropsychological assessments. Over 36 ART regimens were employed, with a focus on ART intensification; almost one-third of the regimens contained Raltegravir (integrase strand transfer inhibitor). The outcomes showed 64.49% full recovery, 30.16% partial recovery, and 4.76% died. When neuropsychological symptoms manifest in PLHIV, monitoring for CSF viral escape is essential, regardless of plasma viral suppression. Personalised treatment strategies, particularly ART intensification, are strongly advised for optimising treatment outcomes in PLHIV diagnosed with CSF HIV escape.

Arterial pulsation dependence of perivascular cerebrospinal fluid flow measured by dynamic diffusion tensor imaging in the human brain.

Perivascular cerebrospinal fluid (pCSF) flow is a key component of the glymphatic system. Arterial pulsation has been proposed as the main driving force of pCSF influx along the superficial and penetrating arteries; however, evidence of this mechanism in humans is limited. We proposed an experimental framework of dynamic diffusion tensor imaging with low b-values and ultra-long echo time (dynDTIlow-b) to capture pCSF flow properties during the cardiac cycle in human brains. Healthy adult volunteers (aged 17-28 years; seven men, one woman) underwent dynDTIlow-b using a 3T scanner (MAGNETOM Prisma, Siemens Healthcare, Erlangen, Germany) with simultaneously recorded cardiac output. The results showed that diffusion tensors reconstructed from pCSF were mainly oriented in the direction of the neighboring arterial flow. When switching from vasoconstriction to vasodilation, the axial and radial diffusivities of the pCSF increased by 5.7 % and 4.94 %, respectively, suggesting that arterial pulsation alters the pCSF flow both parallel and perpendicular to the arterial wall. DynDTIlow-b signal intensity at b=0 s/mm2 (i.e., T2-weighted, [S(b=0 s/mm2)]) decreased in systole, but this change was ∼7.5 % of a cardiac cycle slower than the changes in apparent diffusivity, suggesting that changes in S(b=0 s/mm2) and apparent diffusivity arise from distinct physiological processes and potential biomarkers associated with perivascular space volume and pCSF flow, respectively. Additionally, the mean diffusivities of white matter showed cardiac-cycle dependencies similar to pCSF, although a delay relative to the peak time of apparent diffusivity in pCSF was present, suggesting that dynDTIlow-b could potentially reveal the dynamics of magnetic resonance imaging-invisible pCSF surrounding small arteries and arterioles in white matter; this delay may result from pulse wave propagation along penetrating arteries. In conclusion, the vasodilation-induced increases in axial and radial diffusivities of pCSF and mean diffusivities of white matter are consistent with the notion that arterial pulsation can accelerate pCSF flow in human brain. Furthermore, the proposed dynDTIlow-b technique can capture various pCSF dynamics in artery pulsation.

Does hyperphenylalaninemia induce brain glucose hypometabolism? Cerebral spinal fluid findings in treated adult phenylketonuric patients.

Despite numerous studies in human patients and animal models for phenylketonuria (PKU; OMIM#261600), the pathophysiology of PKU and the underlying causes of brain dysfunction and cognitive problems in PKU patients are not well understood. In this study, lumbar cerebral spinal fluid (CSF) was obtained immediately after blood sampling from early-treated adult PKU patients who had fasted overnight. Metabolite and amino acid concentrations in the CSF of PKU patients were compared with those of non-PKU controls. The CSF concentrations and CSF/plasma ratios for glucose and lactate were found to be below normal, similar to what has been reported for glucose transporter1 (GLUT1) deficiency patients who exhibit many of the same clinical symptoms as untreated PKU patients. CSF glucose and lactate levels were negatively correlated with CSF phenylalanine (Phe), while CSF glutamine and glutamate levels were positively correlated with CSF Phe levels. Plasma glucose levels were negatively correlated with plasma Phe concentrations in PKU subjects, which partly explains the reduced CSF glucose concentrations. Although brain glucose concentrations are unlikely to be low enough to impair brain glucose utilization, it is possible that the metabolism of Phe in the brain to produce phenyllactate, which can be transported across the blood-brain barrier to the blood, may consume glucose and/or lactate to generate the carbon backbone for glutamate. This glutamate is then converted to glutamine and carries the Phe-derived ammonia from the brain to the blood. While this mechanism remains to be tested, it may explain the correlations of CSF glutamine, glucose, and lactate concentrations with CSF Phe.

Management of Tarlov cysts: an uncommon but potentially serious spinal column disease-review of the literature and experience with over 1000 referrals.

Tarlov cysts were thought to be anatomic variants of uncertain etiology and clinical significance when initially described over 80 years ago. They are often detected in routine lumbosacral imaging and generally not reported in a differential diagnosis. There is increasing evidence that at least some Tarlov cysts are symptomatic and can have a significant adverse impact on patients' health and well-being. Women are disproportionately affected with this condition, often presenting with long-standing pain and neurological dysfunctions. Significant gender bias has been a concern in the management of these patients. Unfortunately, there is no consensus on patient selection or management approaches for symptomatic Tarlov cysts. This review article updates information on the prevalence, diagnosis, clinical significance, and treatments of these cysts. Based on these findings and experience with over 1000 patient referrals, a treatment decision algorithm for symptomatic Tarlov cysts was constructed to provide guidance for appropriate management of patients with these complex cysts.

Impact of introducing a new biological matrix into a validated bioanalytical method: Focus on matrix protein content.

International guidance on bioanalytical method validation recommends the practice of partial validation when introducing a new matrix from the same species into a previously fully validated assay. Planning the partial validation protocol should include an evaluation of analyte chemistry, consideration of sample container materials, and a comparison of properties between the relevant biological matrices. Transition of a serum/plasma-validated bioanalytical method to analysis from a low-protein matrix, such as urine, cerebral spinal fluid, or oral fluid can result in inconsistent analyte recovery. The low recovery can potentially be mistaken for signal suppression or lack of drug stability and may be more pronounced in low-concentration or low-volume samples. In addition, adsorption and absorption interactions with containers may be exacerbated in low-protein matrices. Several possibilities exist for mitigating the impact of non-specific binding and low-protein matrices, including surfactants, bovine serum albumin, and ß-cyclodextrin. Finally, higher matrix protein can facilitate analyte stability. Given all this, matrix protein content should not be overlooked when anticipating a partial bioanalytical method validation.

Post-translational modifications linked to preclinical Alzheimer's disease-related pathological and cognitive changes.

INTRODUCTION: In this study, we leverage proteomic techniques to identify communities of proteins underlying Alzheimer's disease (AD) risk among clinically unimpaired (CU) older adults. METHODS: We constructed a protein co-expression network using 3869 cerebrospinal fluid (CSF) proteins quantified by SomaLogic, Inc., in a cohort of participants along the AD clinical spectrum. We then replicated this network in an independent cohort of CU older adults and related these modules to clinically-relevant outcomes. RESULTS: We discovered modules enriched for phosphorylation and ubiquitination that were associated with abnormal amyloid status, as well as p-tau181 (M4: ß = 2.44, p < 0.001, M7: ß = 2.57, p < 0.001) and executive function performance (M4: ß = -2.00, p = 0.005, M7: ß = -2.39, p < 0.001). DISCUSSION: In leveraging CSF proteomic data from individuals spanning the clinical spectrum of AD, we highlight the importance of post-translational modifications for early cognitive and pathological changes.

The Polyanalgesic Consensus Conference (PACC)®: Updates on Clinical Pharmacology and Comorbidity Management in Intrathecal Drug Delivery for Cancer Pain.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise with international representation to establish evidence-based guidance on using intrathecal drug delivery in chronic pain treatment. This Polyanalgesic Consensus Conference (PACC)® project's scope is to provide evidence-based guidance for clinical pharmacology and best practices for intrathecal drug delivery for cancer pain. MATERIALS AND METHODS: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Meeting Abstracts, and Scopus from 2017 (when the PACC last published guidelines) to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations were based on the strength of evidence, and when evidence was scant, recommendations were based on expert consensus. RESULTS: The PACC evaluated the published literature and established evidence- and consensus-based expert opinion recommendations to guide best practices in treating cancer pain. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The PACC recommends best practices regarding the use of intrathecal drug delivery in cancer pain, with an emphasis on managing the unique disease and patient characteristics encountered in oncology. These evidence- and consensus-based expert opinion recommendations should be used as a guide to assist decision-making when clinically appropriate.

Neurofilament light chain in cerebrospinal fluid as a novel biomarker in evaluating both clinical severity and therapeutic response in Niemann-Pick disease type C1.

PURPOSE: Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal disorder caused by pathogenic variants in NPC1. Disease progression is monitored using the NPC Neurological Severity Scale, but there are currently no established validated or qualified biomarkers. Neurofilament light chain (NfL) is being investigated as a biomarker in multiple neurodegenerative diseases. METHODS: Cross-sectional and longitudinal cerebrospinal fluid (CSF) samples were obtained from 116 individuals with NPC1. NfL levels were measured using a solid-phase sandwich enzyme-linked immunosorbent assay and compared with age-appropriate non-NPC1 comparison samples. RESULTS: Median levels of NfL were elevated at baseline (1152 [680-1840] pg/mL) in NPC1 compared with controls (167 [82-372] pg/mL; P < .001). Elevated NfL levels were associated with more severe disease as assessed by both the 17-domain and 5-domain NPC Neurological Severity Score. Associations were also observed with ambulation, fine motor, speech, and swallowing scores. Although treatment with the investigational drug 2-hydroxypropyl-ß-cyclodextrin (adrabetadex) did not decrease CSF NfL levels, miglustat therapy over time was associated with a decrease (odds ratio = 0.77, 95% CI = 0.62-0.96). CONCLUSION: CSF NfL levels are increased in individuals with NPC1, associated with clinical disease severity, and decreased with miglustat therapy. These data suggest that NfL is a biomarker that may have utility in future therapeutic trials.

The morphological and functional diversity of apical microvilli.

Sensory neurons use specialized apical processes to perceive external stimuli and monitor internal body conditions. The apical apparatus can include cilia, microvilli, or both, and is adapted for the functions of the particular cell type. Photoreceptors detect light through a large, modified cilium (outer segment), that is supported by a surrounding ring of microvilli-like calyceal processes (CPs). Although first reported 150 years ago, CPs remain poorly understood. As a basis for future study, we therefore conducted a review of existing literature about sensory cell microvilli, which can act either as the primary sensory detector or as support for a cilia-based detector. While all microvilli are finger-like cellular protrusions with an actin core, the processes vary across cell types in size, number, arrangement, dynamics, and function. We summarize the current state of knowledge about CPs and the characteristics of the microvilli found on inner ear hair cells (stereocilia) and cerebral spinal fluid-contacting neurons, with comparisons to the brush border of the intestinal and renal epithelia. The structure, stability, and dynamics of the actin core are regulated by a complement of actin-binding proteins, which includes both common components and unique features when compared across cell types. Further, microvilli are often supported by lateral links, a glycocalyx, and a defined extracellular matrix, each adapted to the function and environment of the cell. Our comparison of microvillar features will inform further research into how CPs support photoreceptor function, and also provide a general basis for investigations into the structure and functions of apical microvilli found on sensory neurons.

Vaccine Strain and Wild-Type Clades of Varicella-Zoster Virus in Central Nervous System and Non-CNS Disease, New York State, 2004-2019.

Since the introduction of the varicella-zoster virus (VZV) vaccine in the United States in 1995, there has been a dramatic decrease in both the number and severity of varicella cases. However, VZV surveillance data and information on the VZV clade distribution in central nervous system (CNS) disease and non-CNS disease in New York State is not available. To investigate this, cerebrospinal fluid (CSF) samples from patients with encephalitis or meningitis and non-CSF samples from patients with non-CNS disease manifestations consistent with VZV, collected from 2004 to 2019, were tested with molecular VZV assays. A total of 341 CSF and 1,398 non-CSF samples that tested positive by a VZV-specific real-time PCR assay were further characterized as wild-type or vaccine strain by 3 biallelic real-time PCR assays targeting single nucleotide polymorphism (SNP) markers in open reading frame (ORF) 62. Genotyping was then performed on wild-type strains by conventional PCR and sequencing of 500-bp regions in ORFs 21, 22, and 50. Sequence analysis identified clades 1 to 5 in both sample types with a virtually identical clade distribution between CSF and non-CSF samples. In addition, 19 clade 6 and 13 clade 9 samples were detected in non-CSF samples after implementation of an expanded genotyping scheme, including ORF 29, 38, and 67. These clades were not detected in any CSF samples. Finally, a total of 28 vaccine strains were detected, 25 in the non-CSF samples and 3 in the CSF samples. All three cases of vaccine strain with CNS involvement experienced relatively minor symptoms of aseptic meningitis and fully recovered. These results support the evidence that while the VZV vaccine is capable of causing CNS disease, it is still a rare event and symptoms are typically less severe than those caused by wild-type infection.

Antibiotic-impregnated external ventricular drainage for the management of post-hemorrhagic hydrocephalus in low birth weight premature infants following intraventricular hemorrhage.

PURPOSE: This study aims to evaluate the infection rates and catheterization duration of applying antibiotic-impregnated external ventricular drain (EVD) for the treatment of post-hemorrhagic hydrocephalus (PHH) in low birth weight infants (LBWI). METHODS: This retrospective cohort study included 13 preterm LBWI with PHH. Data were collected from the patient's medical charts and included gender, gestational age, birth weight, intraventricular hemorrhage grade, ventriculostomy-associated infection (VAI), and the duration of catheterization. All patients were followed up for at least 6 months after EVD surgery. RESULTS: The mean gestational age at birth was 27 ± 2.5 weeks, and the mean birth weight was 907 ± 220 g. Among all patients with IVH, two (6.7%) had grade 2 IVH, five (38.5%) had grade 3 IVH, and six (46.2%) had grade 4 IVH. EVD surgery was conducted once for six patients, twice for five patients, and three times for two patients. One patient (7.7%) had VAI post-EVD surgery at 14 days. Three patients (23%) expired due to sepsis, shock, and chylous ascites. Seven patients (53.8%) had hydrocephalus and needed a ventriculoperitoneal shunt over the following course. The longest EVD catheterization period was 57 days without sustained VAI. CONCLUSIONS: Antibiotic-impregnated EVD has a similar infection rate with the ventricular access device and ventriculosubgaleal shunt. The risk of VAI was not increased even with the EVD catheterization day approaching 2 months. Our study supports the evidence that antibiotic-impregnated EVD is safe and effective for the management of PHH in LBWI. However, this research has a small sample sized and a retrospective design.

Cerebrospinal Fluid Drainage in Thoracic and Thoracoabdominal Endovascular Aortic Repair: A Survey of Current Clinical Practice in European Medical Centers.

OBJECTIVES: The aim of this survey was to evaluate the daily clinical practice in European hospitals regarding the modalities to prevent spinal cord ischemia, with an emphasis on cerebrospinal fluid drainage (CSFD), in patients undergoing thoracic and thoracoabdominal endovascular repair. DESIGN: A 21-item online survey on current practice of spinal cord protection with an emphasis on CSFD. SETTING: Online service using Castor EDC software. PARTICIPANTS: Members of the European Association of Cardiothoracic Anaesthesiology and Intensive Care and European Society of Vascular Surgeons. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred eighty invitations were sent and 104 were used for analysis. A majority of respondents used a written protocol for spinal cord protection during endovascular thoracic and thoracoabdominal repair (81/104 = 78%). The most common protective measures used were CSFD (79/81 = 98%), controlled hypertension (59/81 = 73%), drugs (11/81 = 14%), and hypothermia (6/81 = 7%). The two most common indications for placement of a spinal catheter were the length of the stent (83/104 = 80%) and location of aneurysm (71/104 = 68%). Preventive placement of the spinal drain (96/104) is the most common approach. In the subgroup of high-volume centers, 86% (12/14) of the respondents used a written protocol and all protocols include CSFD. Ninety-two percent (11/12) had included controlled arterial hypertension in the protocol compared with 70% (48/69) of the non-high-volume centers respondents. CONCLUSIONS: The majority of European centers use a written protocol that includes CSFD. This survey showed the similarities and differences in the management of CSFD in patients undergoing endovascular thoracic and thoracoabdominal repair.

Predicting Shunt Dependency from the Effect of Cerebrospinal Fluid Drainage on Ventricular Size.

BACKGROUND: Prolonged external ventricular drainage (EVD) in patients with subarachnoid hemorrhage (SAH) leads to morbidity, whereas early removal can have untoward effects related to recurrent hydrocephalus. A metric to help determine the optimal time for EVD removal or ventriculoperitoneal shunt (VPS) placement would be beneficial in preventing the prolonged, unnecessary use of EVD. This study aimed to identify whether dynamics of cerebrospinal fluid (CSF) biometrics can temporally predict VPS dependency after SAH. METHODS: This was a retrospective analysis of a prospective, single-center, observational study of patients with aneurysmal SAH who required EVD placement for hydrocephalus. Patients were divided into VPS-dependent (VPS+) and non-VPS dependent groups. We measured the bicaudate index (BCI) on all available computed tomography scans and calculated the change over time (ΔBCI). We analyzed the relationship of ΔBCI with CSF output by using Pearson's correlation. A k-nearest neighbor model of the relationship between ΔBCI and CSF output was computed to classify VPS. RESULTS: Fifty-eight patients met inclusion criteria. CSF output was significantly higher in the VPS+ group in the 7 days post EVD placement. There was a negative correlation between delta BCI and CSF output in the VPS+ group (negative delta BCI means ventricles become smaller) and a positive correlation in the VPS- group starting from days four to six after EVD placement (p < 0.05). A weighted k-nearest neighbor model for classification had a sensitivity of 0.75, a specificity of 0.70, and an area under the receiver operating characteristic curve of 0.80. CONCLUSIONS: The correlation of ΔBCI and CSF output is a reliable intraindividual biometric for VPS dependency after SAH as early as days four to six after EVD placement. Our machine learning model leverages this relationship between ΔBCI and cumulative CSF output to predict VPS dependency. Early knowledge of VPS dependency could be studied to reduce EVD duration in many centers (intensive care unit length of stay).

The Local Inflammatory Profile and Predictors of Treatment Success in Subarachnoid Neurocysticercosis.

BACKGROUND: Subarachnoid neurocysticercosis (SANCC) represents the most severe and difficult to treat form of neurocysticercosis. The inflammatory response contributes significantly to the morbidity and mortality of the disease. This study sought to understand the nature and evolution of the inflammation associated with SANCC, and evaluate for predictors of time to cure. METHODS: There were 16 subjects with SANCC (basilar cistern, sylvian fissure, and/or spinal involvement) during active infection who had cerebrospinal fluid (CSF) cytokine and chemokine profiling, of whom 9 had a second CSF sample at (or following) the time of cure. The relationships between clinical parameters and cytokine/chemokine results were assessed. RESULTS: Compared to pools of healthy donor CSF, those with active SANCC showed a significant (P < .05) increase in chemokines and cytokines associated with Type 1 immunity (interferon [IFN] γ, interleukin [IL] 12p70, C-X-C Motif Ligand 10 CXCL-10); Type 2 immunity (IL-10, IL-13); IFNα2; and the chemokines Macrophage inflammatory protein MIP-1α/CCL3, MIP-1ß/CCL4, and Vascular Endothelial Growth Factor VEGF that appears to be locally (central nervous system [CNS]) produced. Compared to those with active disease, those with CSF taken at the time of cure showed a significant decrease in most of these chemokines and cytokines. Despite this, CSF from cured SANCC patients had levels of IL-10 (P = .039), CXCL-10 (P = .039), and IL-12p70 (P = .044) above those seen in CSF from uninfected subjects. High ratios of IL-12p70/IL-10 early in infections were associated with a shorter time to cure (r = -0.559; P = .027), and a high Taenia solium burden (by quantitative polymerase chain reaction) was associated with longer times to cure (r = 0.84; P = .003). CONCLUSIONS: SANCC is associated with a marked, CNS-localized cytokine-/chemokine-driven inflammatory response that largely decreases with curative therapy, though some analytes persisted above the normal range. The relative balance between proinflammatory and regulatory cytokines may be an important determinant for a cure in SANCC.

Central GLP-1 contributes to improved cognitive function and brain glucose uptake after duodenum-jejunum bypass on obese and diabetic rats.

The improvement of cognitive function following bariatric surgery has been highlighted, yet its underlying mechanisms remain elusive. Finding the improved brain glucose uptake of patients after Roux-en-Y gastric bypass (RYGB), duodenum-jejunum bypass (DJB), and sham surgery (Sham) were performed on obese and diabetic Wistar rats, and intracerebroventricular (ICV) injection of glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira), antagonist exendin-(9-39) (Exe-9), and the viral-mediated GLP-1 receptor (Glp-1r) knockdown (KD) were applied on both groups to elucidate the role of GLP-1 in mediating cognitive function and brain glucose uptake assessed with the Morris water maze (MWM) and positron emission tomography (PET). Insulin and GLP-1 in serum and cerebral spinal fluid (CSF) were measured, and the expression of glucose uptake-related proteins including glucose transporter 1 (GLUT-1), GLUT-4, phospho-Akt substrate of 160kDa (pAS160), AS160, Rab10, Myosin-Va as well as the c-fos marker in the brain were examined. Along with augmented glucose homeostasis following DJB, central GLP-1 was correlated with the improved cognitive function and ameliorated brain glucose uptake, which was further confirmed by the enhancive role of Lira on both groups whereas the Exe-9 and Glp-1r KD were opposite. Known to activate insulin-signaling pathways, central GLP-1 contributes to improved cognitive function and brain glucose uptake after DJB.NEW & NOTEWORTHY The improvement of cognitive function following bariatric surgery has been highlighted while its mechanisms remain elusive. The brain glucose uptake of patients was improved after RYGB, and the DJB and sham surgery performed on obese and diabetic Wistar rats revealed that the elevated central GLP-1 contributes to the dramatic improvement of cognitive function, brain glucose uptake, transport, glucose sensing, and neuronal activation.

Intracranial Hemorrhage After Endovascular Repair of Thoracoabdominal Aortic Aneurysm.

BACKGROUND: Intracranial hemorrhage (ICH) is a rare but devastating complication of thoracoabdominal aortic aneurysm (TAAA) repair with fenestrated/branched endograft (f/bEVAR). The cerebrospinal fluid drainage (CSFD) is considered one of the leading causes; however, other possible concomitant factors have not been individualized yet. The aim of the present work was to evaluate the pattern of ICH events after f/bEVAR for TAAA and to identify possible associated factors. MATERIALS AND METHODS: All f/bEVAR procedures for TAAA performed in a single academic center from 2012 to 2020 were evaluated. ICH was assessed by cerebral computed tomography if neurological symptoms arose. Pre-, intra-, and postoperative characteristics were analyzed in order to identify possible factors associated. RESULTS: A total of 135 f/bEVAR were performed for 72 (53%) type I, II, III and 63 (47%) type IV TAAA; 74 (55%) were staged procedures, 101 (73%) required CSFD, and 24 (18%) were performed urgently. The overall 30-day mortality was 8% (5% in elective cases); spinal-cord ischemia occurred in 11(8%) and ICH in 8 (6%) patients. All ICH occurred in patients with CSFD. ICH occurred intraoperatively in 1 case, inter-stage in 4 and after F/BEVAR completion in 3, after a median of 6 days the completion stage. Three (38%) of 8 patients with ICH died at 30 days and ICH was associated with 30-day mortality: odds ratio (OR) 13.2, 95% confidence interval (CI): 2.3-76, p=0.01. The analysis of the perioperative characteristics identified platelet reduction >60% (OR 11, 95% CI 1.6-77, p=0.03), chronic kidney disease (16% vs 0%, p=0.002), and total volume of liquor drained >50 mL (OR 8.1, 95% CI 1.1-69, p=0.03) as associated with ICH. CONCLUSIONS: Current findings may suggest that ICH is a potential lethal complication of the endovascular treatment for TAAAs and it mainly occurs in patients with CSFD. High-volume liquor drainage, platelet reduction, and chronic kidney disease seems increase significantly the risk of ICH and should be considered during the perioperative period and for further studies.

Clinical-MRI radiomics enables the prediction of preoperative cerebral spinal fluid dissemination in children with medulloblastoma.

BACKGROUND: Medulloblastoma (MB) is the most common pediatric embryonal tumor. Accurate identification of cerebral spinal fluid (CSF) dissemination is important in prognosis prediction. Both MRI of the central nervous system (CNS) and CSF cytology will appear false positive and negative. Our objective was to investigate the added value of preoperative-enhanced T1-weighted image-based radiomic features to clinical characteristics in predicting preoperative CSF dissemination for children with MB. MATERIALS AND METHODS: This retrospective study included 84 children with histopathologically confirmed MB between November 2006 and November 2018 (training cohort, n=60; internal validation cohort, n=24). A set of cases between December 2018 and February 2020 were used for external validation (n=40). The children with normal head and spine magnetic resonance images (MRI) and no subsequent dissemination in 1 year were diagnosed as non-CSF dissemination. The CSF dissemination was manifested as intracranial or intraspinal nodular-enhanced lesions. Clinical features were collected, and conventional MRI features of preoperative head MRI examinations were evaluated. A total of 385 radiomic features were extracted from preoperative-enhanced T1-weighted images. Minimum redundancy, maximum correlation, and least absolute shrinkage and selection operator were performed to select the features with the best performance in predicting preoperative CSF dissemination. A combined clinical-MRI radiomic prediction model was developed using multivariable logistic regression. Receiver operating curve analysis (ROC) was used to validate the predictive performance. Nomogram and decision curve analysis (DCA) were developed to evaluate the clinical utility of the combined model. RESULTS: One clinical and nine radiomic features were selected for predicting preoperative CSF dissemination. The combined model incorporating clinical and radiomic features had the best predictive performance in the training cohort with an AUC of 0.89. This was validated in the internal and external cohorts with AUCs of 0.87 and 0.73. The clinical utility of the model was confirmed by a clinical-MRI radiomic nomogram and DCA. CONCLUSIONS: The combined model incorporating clinical, conventional MRI, and radiomic features could be applied to predict preoperative CSF dissemination for children with MB as a noninvasive biomarker, which could aid in risk evaluation.

Comparison of dural closure methods for dural repair to reduce the incidence of cerebrospinal fluid leakage.

PURPOSE: Cerebrospinal fluid leakage (CSFL) is a common complication during spinal surgery. This study aimed to compare dural closure with different suture types, sizes, and techniques, and adhesives to reduce the occurrence of CSFL. MATERIALS AND METHODS: Using a pig spine model, the PDS II 4-0, 5-0, 6-0, Vicryl 4-0, 5-0, 6-0, and Prolene 4-0, 5-0, 6-0 sutures were compared by calculating the permeability after suturing. Spraying bioprotein glue was also tried. Next, 120 patients who underwent surgery for intraspinal subdural tumors were enrolled and received 5-0 PDSII, Vicryl, or Prolene for dura repair. RESULTS: In the animal model study, Vicryl 5-0 showed a reduced leakage flow rate compared with 5-0 Prolene and 5-0 PDS II. In the clinical study, postoperative drainage in the Vicryl group was smaller than that in the other groups during the first 3 days after surgery (p < 0.05). Drainage volume of patients with postoperative cerebrospinal fluid leakage in the Vicryl group was smaller than that in the other groups during the first 3 days after surgery (p < 0.05).There were 12 patients (23.1%, 12/52) in the Vicryl group, 20 patients (55.6%, 20/36) in the PDS group, and 16 patients (50.0%, 16/32) in the Prolene group who had CSFL.The incidence of CSFL was significantly reduced in Vicryl group compared with the other groups(P < 0.05). CONCLUSIONS: 5-0 Vicryl sutures significantly reduced the dural leakage flow rate in an animal spine model. Fibrin glue can reinforce dural repair after surgery. 5-0 Vicryl was associated with a lower occurrence of CSFL in patients.

A Quality Improvement Project to Reduce Antibiotic Utilization and Ancillary Laboratory Tests in the Appraisal of Early-Onset Sepsis in the NICU.

BACKGROUND: Diagnosis and treatment of early-onset sepsis (EOS) of the newborn remains a controversial issue among providers due to the non-infectious symptomology which exists in the newborn period. METHODS: Pre/post interventional quality improvement project in a level III NICU to reduce antibiotic utilization and ancillary laboratory tests with the introduction of an evidence-based guideline for the evaluation of EOS in the NICU. RESULTS: Primary outcome measures include mean number of empiric antibiotic treatment days and utilization rate (AUR), number of laboratory tests ordered, and incidence of unwarranted antibiotic therapy beyond the 48-h rule out period. Mean empiric antibiotic treatment days decreased from 2.94 to 1.58 days and overall antibiotic use decreased from 73.7% to 57.1%. Likewise, the mean AUR decreased from 212.5 to 147.6 days of therapy per 1000 patient days. There was an 86% decline in the number of ancillary tests and unwarranted antibiotic use beyond 48- h was reduced by 74%. DISCUSSION: Guidelines for EOS of the newborn should include a thorough baseline evaluation of the drivers of antibiotic use to create an evidence-based foundation. Reducing unnecessary antibiotic use and EOS evaluations in a safe and effective manner have the potential to lower consumer and healthcare expenditures while improving the long-term health of the newborn in the NICU. CONCLUSIONS: These findings emphasize the importance of implementing an evidence-based protocol for antibiotic stewardship in the NICU. With further research there is the potential to improve the healthcare of newborns while reducing expenditures in a safe, effective evaluation of EOS in the newborn population.