Protein N-glycans in Healthy and Sclerotic Glomeruli in Diabetic Kidney Disease.

BACKGROUND: Diabetes is expected to directly impact renal glycosylation, yet to date, there has not been a comprehensive evaluation of alterations in N-glycan composition in the glomeruli of patients with diabetic kidney disease (DKD). METHODS: We used untargeted mass spectrometry imaging to identify N-glycan structures in healthy and sclerotic glomeruli in FFPE sections from needle biopsies of five patients with DKD and three healthy kidney samples. Regional proteomics was performed on glomeruli from additional biopsies from the same patients to compare the abundances of enzymes involved in glycosylation. Secondary analysis of single nuclei transcriptomics (snRNAseq) data was used to inform on transcript levels of glycosylation machinery in different cell types and states. RESULTS: We detected 120 N-glycans, and among them identified twelve of these protein post-translated modifications that were significantly increased in glomeruli. All glomeruli-specific N-glycans contained an N-acetyllactosamine (LacNAc) epitope. Five N-glycan structures were highly discriminant between sclerotic and healthy glomeruli. Sclerotic glomeruli had an additional set of glycans lacking fucose linked to their core, and they did not show tetra-antennary structures that are common in healthy glomeruli. Orthogonal omics analyses revealed lower protein abundance and lower gene expression involved in synthesizing fucosylated and branched N-glycans in sclerotic podocytes. In snRNAseq and regional proteomics analyses, we observed that genes and/or proteins involved in sialylation and LacNAc synthesis were also downregulated in DKD glomeruli, but this alteration remained undetectable by our spatial N-glycomics assay. CONCLUSIONS: Integrative spatial glycomics, proteomics, and transcriptomics revealed protein N-glycosylation characteristic of sclerotic glomeruli in DKD.

Postoperative Adjacent Segment Disease in Minimally Invasive Transforaminal Lumbar Interbody Fusion with Adjacent Laminectomy for Grade I-II Spondylolisthesis and Adjacent Spinal Stenosis.

BACKGROUND AND OBJECTIVES: Studies have demonstrated increased risk of adjacent segment disease (ASD) after open fusion with adjacent-level laminectomy, with rates ranging from 16%-47%, potentially related to disruption of the posterior ligamentous complex. Minimally invasive surgical (MIS) approaches may offer a more durable result. We report institutional outcomes of simultaneous MIS transforaminal lumbar interbody fusion (MISTLIF) and adjacent-level laminectomy for patients with low grade spondylolisthesis and ASD. METHODS: Retrospective analysis was performed on patients who underwent MISTLIF with adjacent level laminectomy to treat grade I-II spondylolisthesis with adjacent stenosis at a single institution from 2007-2022. RESULTS: A total of 34 patients met criteria, with mean follow-up of 23.1 months. In total, 37 levels were fused and 45 laminectomies performed. In this group, 21 patients received a single level laminectomy and single-level MISTLIF, 10 patients received a 2-level laminectomy and single-level MISTLIF, 2 patients received a single-level laminectomy and 2-level MISTLIF, and 1 patient received a 2-level laminectomy and 2-level MISTLIF. Three (8.8%) patients experienced clinically significant postoperative ASD requiring reoperation. Three other patients required reoperation for other reasons. Multiple logistic regression did not reveal any association between development of ASD and surgical covariates. CONCLUSION: MISTLIF with adjacent-level laminectomy demonstrated a favorable safety profile with rates of postoperative ASD lower than published rates after open fusion and on par with the published rates of ASD from MISTLIF alone. Future prospective studies may better elucidate the durability of adjacent-level laminectomies when performed alongside MISTLIF, but retrospective data suggests it is safe and durable.

Mycobacterium xenopi vertebral osteomyelitis in a patient with systemic lupus erythematosus: illustrative case.

BACKGROUND: Mycobacterium xenopi is a common nontuberculous Mycobacterium (NTM) that is slow growing and an infrequent cause of infection. When infections do occur, it is by exposure to contaminated soil or water or to infectious aerosols. Nontuberculous mycobacterial infections in the spine are exceedingly rare. Risk factors can include immunosuppression, particularly human immunodeficiency virus; however, other systemic diseases such as systemic lupus erythematosus (SLE) have been reported. OBSERVATIONS: The authors report a case of cord compression due to M. xenopi vertebral osteomyelitis with an epidural abscess in a patient with SLE on hydroxychloroquine and recent steroid use. The authors explore the presentation of a patient who developed acute neurological deficits concerning for spinal pathology secondary to NTM. Although considered a rare occurrence, patients with autoimmune pathologies are susceptible to infection by unusual organisms. Standard treatment of autoimmune diseases can predispose patients to infection and warrant surgical correction to prevent long-term neurological deficits. LESSONS: There is still much work and research to be done in the exploration and understanding of nontuberculous mycobacterial infection, pathophysiology, and treatment in the immunocompetent population and in patients with autoimmune disorders.

Upstream Effects: Intraoperative Migration of Intradural Extramedullary Tumor After Non-Adjacent Level Stenosis Decompression.

A 74-year-old man with back pain, foot numbness, and hip/thigh radiculopathy was found to have an L1-L2 intradural extramedullary neoplasm and severe L4-L5 stenosis. L4-L5 minimally invasive laminectomy for decompression and concomitant L1-L2 minimally invasive laminectomy for tumor resection were planned. L4-L5 laminectomy was completed first followed by the L1-L2 laminectomy. On extensive intradural exploration at L1-L2, no neoplasm was found. Immediate postoperative imaging showed that the intradural extramedullary tumor had migrated caudally by nearly a complete spinal level, presumably due to changes in cerebrospinal fluid pressure and resultant shift in intradural contents after the L4-L5 laminectomy. Successful resection of the intradural extramedullary tumor was performed, with improvement in the patient's symptoms.

Quantitative analysis of high-frequency activity in neonatal EEG.

OBJECTIVE: To determine the presence and potential utility of independent high-frequency activity recorded from scalp electrodes in the electroencephalogram (EEG) of newborns. METHODS: We compare interburst intervals and continuous activity at different frequencies for EEGs retrospectively recorded at 256 Hz from 4 newborn groups: 1) 36 preterms (<32 weeks' gestational age, GA); 2) 12 preterms (32-37 weeks' GA); 3) 91 healthy full terms; 4) 15 full terms with hypoxic-ischemic encephalopathy (HIE). At 4 standard frequency bands (delta, 0.5-3 Hz; theta, 3-8 Hz; alpha, 8-15 Hz; beta, 15-30 Hz) and 3 higher-frequency bands (gamma1, 30-48 Hz; gamma2, 52-99 Hz; gamma3, 107-127 Hz), we compared power spectral densities (PSDs), quantitative features, and machine learning model performance. Feature selection and further machine learning methods were performed on one cohort. RESULTS: We found significant (P < 0.01) differences in PSDs, quantitative analysis, and machine learning modelling at the higher-frequency bands. Machine learning models using only high-frequency features performed best in preterm groups 1 and 2 with a median (95% confidence interval, CI) Matthews correlation coefficient (MCC) of 0.71 (0.12-0.88) and 0.66 (0.36-0.76) respectively. Interburst interval-detector models using both high- and standard-bandwidths produced the highest median MCCs in all four groups. High-frequency features were largely independent of standard-bandwidth features, with only 11/84 (13.1%) of correlations statistically significant. Feature selection methods produced 7 to 9 high-frequency features in the top 20 feature set. CONCLUSIONS: This is the first study to identify independent high-frequency activity in newborn EEG using in-depth quantitative analysis. Expanding the EEG bandwidths of analysis has the potential to improve both quantitative and machine-learning analysis, particularly in preterm EEG.

Machine Learning Detects Intraventricular Haemorrhage in Extremely Preterm Infants.

OBJECTIVE: To test the potential utility of applying machine learning methods to regional cerebral (rcSO2) and peripheral oxygen saturation (SpO2) signals to detect brain injury in extremely preterm infants. STUDY DESIGN: A subset of infants enrolled in the Management of Hypotension in Preterm infants (HIP) trial were analysed (n = 46). All eligible infants were <28 weeks' gestational age and had continuous rcSO2 measurements performed over the first 72 h and cranial ultrasounds performed during the first week after birth. SpO2 data were available for 32 infants. The rcSO2 and SpO2 signals were preprocessed, and prolonged relative desaturations (PRDs; data-driven desaturation in the 2-to-15-min range) were extracted. Numerous quantitative features were extracted from the biosignals before and after the exclusion of the PRDs within the signals. PRDs were also evaluated as a stand-alone feature. A machine learning model was used to detect brain injury (intraventricular haemorrhage-IVH grade II-IV) using a leave-one-out cross-validation approach. RESULTS: The area under the receiver operating characteristic curve (AUC) for the PRD rcSO2 was 0.846 (95% CI: 0.720-0.948), outperforming the rcSO2 threshold approach (AUC 0.593 95% CI 0.399-0.775). Neither the clinical model nor any of the SpO2 models were significantly associated with brain injury. CONCLUSION: There was a significant association between the data-driven definition of PRDs in rcSO2 and brain injury. Automated analysis of PRDs of the cerebral NIRS signal in extremely preterm infants may aid in better prediction of IVH compared with a threshold-based approach. Further investigation of the definition of the extracted PRDs and an understanding of the physiology underlying these events are required.

Perception of frailty in spinal metastatic disease: international survey of the AO Spine community.

OBJECTIVE: Frailty has not been clearly defined in the context of spinal metastatic disease (SMD). Given this, the objective of this study was to better understand how members of the international AO Spine community conceptualize, define, and assess frailty in SMD. METHODS: The AO Spine Knowledge Forum Tumor conducted an international cross-sectional survey of the AO Spine community. The survey was developed using a modified Delphi technique and was designed to capture preoperative surrogate markers of frailty and relevant postoperative clinical outcomes in the context of SMD. Responses were ranked using weighted averages. Consensus was defined as ≥ 70% agreement among respondents. RESULTS: Results were analyzed for 359 respondents, with an 87% completion rate. Study participants represented 71 countries. In the clinical setting, most respondents informally assess frailty and cognition in patients with SMD by forming a general perception based on clinical condition and patient history. Consensus was attained among respondents regarding the association between 14 preoperative clinical variables and frailty. Severe comorbidities, extensive systemic disease burden, and poor performance status were most associated with frailty. Severe comorbidities associated with frailty included high-risk cardiopulmonary disease, renal failure, liver failure, and malnutrition. The most clinically relevant outcomes were major complications, neurological recovery, and change in performance status. CONCLUSIONS: The respondents recognized that frailty is important, but they most commonly evaluate it based on general clinical impressions rather than using existing frailty tools. The authors identified numerous preoperative surrogate markers of frailty and postoperative clinical outcomes that spine surgeons perceived as most relevant in this population.

Comparison of Perioperative Complications After Anterior-Posterior Versus Posterior-Anterior-Posterior Cervical Fusion: A Retrospective Review of 153 Consecutive Cases.

BACKGROUND: Although published data support the utilization of circumferential fusion to treat select cervical spine pathologies, it is unclear whether the posterior-anterior-posterior (PAP) fusion has increased risks compared with the anterior-posterior fusion. OBJECTIVE: To evaluate the differences in perioperative complications between the 2 circumferential cervical fusion approaches. METHODS: One hundred fifty-three consecutive adult patients who underwent single-staged circumferential cervical fusion for degenerative pathologies from 2010 to 2021 were retrospectively reviewed. Patients were stratified into the anterior-posterior ( n = 116) and PAP ( n = 37) groups. The primary outcomes assessed were major complications, reoperation, and readmission. RESULTS: Although the PAP group was older ( P = .024), predominantly female ( P = .024), with higher baseline neck disability index ( P = .026), cervical sagittal vertical axis ( P = .001), and previous cervical operation rate ( P < .00001), the major complication, reoperation, and readmission rates were not significantly different from the 360° group. Although the PAP group had higher urinary tract infection ( P = .043) and transfusion ( P = .007) rates, higher estimated blood loss ( P = .034), and longer operative times ( P < .00001), these differences were insignificant after the multivariable analysis. Overall, operative time was associated with older age (odds ratio [OR] 17.72, P = .042), atrial fibrillation (OR 158.30, P = .045), previous cervical operation (OR 5.05, P = .051), and lower baseline C1 - 7 lordosis (OR 0.93, P = .007). Higher estimated blood loss was associated with older age (OR 1.13, P = .005), male gender (OR 323.31, P = .047), and higher baseline cervical sagittal vertical axis (OR 9.65, P = .022). CONCLUSION: Despite some differences in preoperative and intraoperative variables, this study suggests both circumferential approaches have comparable reoperation, readmission, and complication profiles, all of which are high.

Neonatal EEG graded for severity of background abnormalities in hypoxic-ischaemic encephalopathy.

This report describes a set of neonatal electroencephalogram (EEG) recordings graded according to the severity of abnormalities in the background pattern. The dataset consists of 169 hours of multichannel EEG from 53 neonates recorded in a neonatal intensive care unit. All neonates received a diagnosis of hypoxic-ischaemic encephalopathy (HIE), the most common cause of brain injury in full term infants. For each neonate, multiple 1-hour epochs of good quality EEG were selected and then graded for background abnormalities. The grading system assesses EEG attributes such as amplitude, continuity, sleep-wake cycling, symmetry and synchrony, and abnormal waveforms. Background severity was then categorised into 4 grades: normal or mildly abnormal EEG, moderately abnormal EEG, majorly abnormal EEG, and inactive EEG. The data can be used as a reference set of multi-channel EEG for neonates with HIE, for EEG training purposes, or for developing and evaluating automated grading algorithms.

Parent-led massage and sleep EEG for term-born infants: A randomized controlled parallel-group study.

AIM: To examine the impact of parent-led massage on the sleep electroencephalogram (EEG) features of typically developing term-born infants at 4 months. METHOD: Infants recruited at birth were randomized to intervention (routine parent-led massage) and control groups. Infants had a daytime sleep EEG at 4 months and were assessed using the Griffiths Scales of Child Development, Third Edition at 4 and 18 months. Comparative analysis between groups and subgroup analysis between regularly massaged and never-massaged infants were performed. Groups were compared for sleep stage, sleep spindles, quantitative EEG (primary analysis), and Griffiths using the Mann-Whitney U test. RESULTS: In total, 179 out of 182 infants (intervention: 83 out of 84; control: 96 out of 98) had a normal sleep EEG. Median (interquartile range) sleep duration was 49.8 minutes (39.1-71.4) (n = 156). A complete first sleep cycle was seen in 67 out of 83 (81%) and 72 out of 96 (75%) in the intervention and control groups respectively. Groups did not differ in sleep stage durations, latencies to sleep and to rapid eye movement sleep. Sleep spindle spectral power was greater in the intervention group in main and subgroup analyses. The intervention group showed greater EEG magnitudes, and lower interhemispherical coherence on subgroup analyses. Griffiths assessments at 4 months (n = 179) and 18 months (n = 173) showed no group differences in the main and subgroup analyses. INTERPRETATION: Routine massage is associated with distinct functional brain changes at 4 months. WHAT THIS PAPER ADDS: Routine massage of infants is associated with differences in sleep electroencephalogram biomarkers at 4 months. Massaged infants had higher sleep spindle spectral power, greater sleep EEG magnitudes, and lower interhemispherical coherence. No differences between groups were observed in total nap duration or first cycle macrostructure.

Characteristics of Potential and Actual Living Kidney Donors: A Single-center Experience.

BACKGROUND: There are limited data and no national capture of barriers associated with initiating and completing the donation process for potential living kidney donors (LKDs). METHODS: We performed a retrospective analysis of 3001 intake forms completed by prospective LKDs from 2016 to 2019 at a single transplant center. We analyzed data from all potential donors who completed the intake until they became ineligible or withdrew or donation was complete. We used univariate and multivariate models to evaluate independent factors associated with donation at various stages in the donation process. RESULTS: The donation process was deconstructed into 5 steps: intake form, immunologic compatibility testing, clinic evaluation, selection committee review, and donation. The highest percentage of potential donors dropped out after completing the intake form, primarily because of not responding to the follow-up phone call (22.6%). Of 455 potential LKDs that completed immunologic compatibility testing, 36% were ABO or crossmatch incompatible. One-hundred eighty-eight (7.5%) of all LKD applicants reached donation, the majority of whom were White (91.0%) and female (63.8%). CONCLUSIONS: A minority of LKD applicants make it to donation. Our ability to track all potential LKDs from the initial touch point to the transplant center will help us develop interventions to address barriers to a successful donation.

Machine learning for the early prediction of infants with electrographic seizures in neonatal hypoxic-ischemic encephalopathy.

OBJECTIVE: To assess if early clinical and electroencephalography (EEG) features predict later seizure development in infants with hypoxic-ischemic encephalopathy (HIE). METHODS: Clinical and EEG parameters <12 h of birth from infants with HIE across eight European Neonatal Units were used to develop seizure-prediction models. Clinical parameters included intrapartum complications, fetal distress, gestational age, delivery mode, gender, birth weight, Apgar scores, assisted ventilation, cord pH, and blood gases. The earliest EEG hour provided a qualitative analysis (discontinuity, amplitude, asymmetry/asynchrony, sleep-wake cycle [SWC]) and a quantitative analysis (power, discontinuity, spectral distribution, inter-hemispheric connectivity) from full montage and two-channel amplitude-integrated EEG (aEEG). Subgroup analysis, only including infants without anti-seizure medication (ASM) prior to EEG was also performed. Machine-learning (ML) models (random forest and gradient boosting algorithms) were developed to predict infants who would later develop seizures and assessed using Matthews correlation coefficient (MCC) and area under the receiver-operating characteristic curve (AUC). RESULTS: The study included 162 infants with HIE (53 had seizures). Low Apgar, need for ventilation, high lactate, low base excess, absent SWC, low EEG power, and increased EEG discontinuity were associated with seizures. The following predictive models were developed: clinical (MCC 0.368, AUC 0.681), qualitative EEG (MCC 0.467, AUC 0.729), quantitative EEG (MCC 0.473, AUC 0.730), clinical and qualitative EEG (MCC 0.470, AUC 0.721), and clinical and quantitative EEG (MCC 0.513, AUC 0.746). The clinical and qualitative-EEG model significantly outperformed the clinical model alone (MCC 0.470 vs 0.368, p-value .037). The clinical and quantitative-EEG model significantly outperformed the clinical model (MCC 0.513 vs 0.368, p-value .012). The clinical and quantitative-EEG model for infants without ASM (n = 131) had MCC 0.588, AUC 0.832. Performance for quantitative aEEG (n = 159) was MCC 0.381, AUC 0.696 and clinical and quantitative aEEG was MCC 0.384, AUC 0.720. SIGNIFICANCE: Early EEG background analysis combined with readily available clinical data helped predict infants who were at highest risk of seizures, hours before they occur. Automated quantitative-EEG analysis was as good as expert analysis for predicting seizures, supporting the use of automated assessment tools for early evaluation of HIE.

T-cell receptor diversity in minimal change disease in the NEPTUNE study.

BACKGROUND: Minimal change disease (MCD) is the major cause of childhood idiopathic nephrotic syndrome, which is characterized by massive proteinuria and debilitating edema. Proteinuria in MCD is typically rapidly reversible with corticosteroid therapy, but relapses are common, and children often have many adverse events from the repeated courses of immunosuppressive therapy. The pathobiology of MCD remains poorly understood. Prior clinical observations suggest that abnormal T-cell function may play a central role in MCD pathogenesis. Based on these observations, we hypothesized that T-cell responses to specific exposures or antigens lead to a clonal expansion of T-cell subsets, a restriction in the T-cell repertoire, and an elaboration of specific circulating factors that trigger disease onset and relapses. METHODS: To test these hypotheses, we sequenced T-cell receptors in fourteen MCD, four focal segmental glomerulosclerosis (FSGS), and four membranous nephropathy (MN) patients with clinical data and blood samples drawn during active disease and during remission collected by the Nephrotic Syndrome Study Network (NEPTUNE). We calculated several T-cell receptor diversity metrics to assess possible differences between active disease and remission states in paired samples. RESULTS: Median productive clonality did not differ between MCD active disease (0.0083; range: 0.0042, 0.0397) and remission (0.0088; range: 0.0038, 0.0369). We did not identify dominant clonotypes in MCD active disease, and few clonotypes were shared with FSGS and MN patients. CONCLUSIONS: While these data do not support an obvious role of the adaptive immune system T-cells in MCD pathogenesis, further study is warranted given the limited sample size. A higher resolution version of the Graphical abstract is available as Supplementary information.

Comparison of Fusion versus Nonunion After 4-Level and 5-Level Anterior Cervical Diskectomy and Fusion With Anterior Plate Fixation.

BACKGROUND: Nonunion remains a concern in multilevel anterior cervical discectomy and fusion (ACDF), yet there are limited data on nonunion after 4 to 5-level ACDF. In fact, the largest series on 4-level or 5-level ACDF focused specifically on the swallowing outcomes. OBJECTIVE: To assess nonunion after 4 to 5-level ACDF. METHODS: Forty-one patients treated with 4 to 5-level ACDF with minimum of 12-month radiographic follow-up were retrospectively reviewed. Nonunion was found in 25 patients (61%) and 42 levels (25%) and complete fusion in 16 (39%) patients and 126 levels (75%). The 2 groups were further compared. RESULTS: One-level nonunion was by far the most common pattern compared with multilevel nonunion. Nonunion occurred more frequently at the caudal than the cranial or middle segments ( P < .0001). There were significantly more subsidence ( P < .0001) and screw fractures/pullouts ( P < .0001) in the nonunion compared with the fusion group. The symptomatic patients were significantly younger than the asymptomatic patients ( P = .044). The symptomatic levels were significantly more than asymptomatic levels ( P = .048). Equal proportion of patients implanted with allograft and polyetheretherketone had nonunion. However, there were markedly more nonunion than fused levels with allograft and more fused than nonunion levels with polyetheretherketone ( P = .023). The reoperation rate was 24.4% and mostly due to nonunion. There were no reoperations within 90 days of the primary surgery. CONCLUSION: The nonunion rate for 4-level and 5-level ACDF may be higher than previously reported. Symptomatic nonunion remains a major reason for reoperation after multilevel ACDF. Baseline characteristics that negatively affect fusion may be obviated by careful patient selection.

Agreement of Cardiac Output Estimates between Electrical Cardiometry and Transthoracic Echocardiography in Very Preterm Infants.

INTRODUCTION: The aim was to evaluate the agreement between cardiac output estimates obtained by electrical cardiometry (EC) and transthoracic echocardiography (TTE) in very preterm infants. METHODS: This is a single-center prospective observational study in infants born<32 weeks gestational age within 48 h of birth. Continuous EC was recorded and simultaneous TTE obtained on day 1 and day 2 of life. Blinded TTE measurements were performed within a 10 s timeframe using beat-to-beat EC data. The primary outcome was %error of left ventricular (LV) output in milliliters per kilogram per minute (cardiac index (CI)) obtained by TTE compared to LV-CI from EC. Secondary outcome parameters were bias, %bias, limits of agreement and include measures of right ventricular (RV) output and LV systolic time intervals. RESULTS: Analysis was performed for 34 infants (median (IQR) gestational age 29 + 0 (24 + 5 to 30 + 6) weeks + days, birthweight 960 (748 to 1,490) grams) including 44 pairwise LV output measurements on 24 participants (22 on day 1 and day 2). The %error was 54% for LV-CI (EC: 214 (38) mL/kg/min vs. TTE: 163 (47) mL/kg/min). The %error was 78% for RV-CI (EC: 213 (37) mL/kg/min vs. TTE: 241 (77) mL/kg/min). While only LV-CI values affected LV-CI bias, signal quality, heart rate, and RV-CI values affected RV-CI bias. CONCLUSION: EC is not interchangeable with TTE to estimate indices of LV or RV output in very preterm infants within the first 48 h postnatally. EC may not measure LV output distinctly in very preterm infants with intra- and extracardiac shunts.

Evolution of early cerebral NIRS in hypoxic ischaemic encephalopathy.

AIM: To describe early cerebral oxygenation (cSO2 ) and fractional tissue oxygen extraction (FTOE) values and their evolution over the first days of life in infants with all grades of hypoxic-ischaemic encephalopathy (HIE) and to determine whether cSO2 and FTOE measured early (6 and 12 h) can predict short-term outcome. METHODS: Prospective, observational study of cerebral near-infrared spectroscopy (NIRS) in infants >36 weeks' gestation with HIE. Ten one-hour epochs of cSO2 and FTOE were extracted for each infant over the first 84 h. Infants with moderate and severe HIE received therapeutic hypothermia (TH). Abnormal outcome was defined as abnormal magnetic resonance imaging (MRI) and/or death. RESULTS: Fifty-eight infants were included (28 mild, 24 moderate, 6 severe). Median gestational age was 39.9 weeks (IQR 38.1-40.7) and birthweight was 3.35 kgs (IQR 2.97-3.71). cSO2 increased and FTOE decreased over the first 24 h in all grades of HIE. Compared to the moderate group, infants with mild HIE had significantly higher cSO2 at 6 h (p = 0.003), 9 h (p = 0.009) and 12 h (p = 0.032) and lower FTOE at 6 h (p = 0.016) and 9 h (0.029). cSO2 and FTOE at 6 and 12 h did not predict abnormal outcome. CONCLUSION: Infants with mild HIE have higher cSO2 and lower FTOE than those with moderate or severe HIE in the first 12 h of life. cSO2 increased in all grades of HIE over the first 24 h regardless of TH status.

Essential role of Wtip in mouse development and maintenance of the glomerular filtration barrier.

Wilms' tumor interacting protein (Wtip) has been implicated in cell junction assembly and cell differentiation and interacts with proteins in the podocyte slit diaphragm, where it regulates podocyte phenotype. To define Wtip expression and function in the kidney, we created a Wtip-deleted mouse model using ß-galactosidase-neomycin (ß-geo) gene trap technology. Wtip gene trap mice were embryonic lethal, suggesting additional developmental roles outside kidney function. Using ß-geo heterozygous and normal mice, Wtip expression was identified in the developing kidneys, heart, and eyes. In the kidney, expression was restricted to podocytes, which appeared initially at the capillary loop stage coinciding with terminal podocyte differentiation. Heterozygous mice had an expected lifespan and showed no evidence of proteinuria or glomerular pathology. However, heterozygous mice were more susceptible to glomerular injury than wild-type littermates and developed more significant and prolonged proteinuria in response to lipopolysaccharide or adriamycin. In normal human kidneys, WTIP expression patterns were consistent with observations in mice and were lost in glomeruli concurrent with loss of synaptopodin expression in disease. Mechanistically, we identified the Rho guanine nucleotide exchange factor 12 (ARHGEF12) as a binding partner for WTIP. ARHGEF12 was expressed in human podocytes and formed high-affinity interactions through their LIM- and PDZ-binding domains. Our findings suggest that Wtip is essential for early murine embryonic development and maintaining normal glomerular filtration barrier function, potentially regulating slit diaphragm and foot process function through Rho effector proteins.NEW & NOTEWORTHY This study characterized dynamic expression patterns of Wilms' tumor interacting protein (Wtip) and demonstrates the novel role of Wtip in murine development and maintenance of the glomerular filtration barrier.

Recurrent IgG4-Related Meningeal Disease of the Cervicothoracic Spine: A Case Report and Review of the Literature.

Background: IgG4-related disease is a rare, recently recognized chronic inflammatory disease. IgG4-related hypertrophic pachymeningitis (IgG4-RHP) of the central nervous system predominantly involves the cranial meninges. Spinal involvement remains rare. Objective: We report a case of recurrent cervicothoracic IgG4-RHP and review the surgical literature. Methods and Materials: A 35-year-old woman presented with a 6-month history of neck and right shoulder pain, progressive right triceps weakness and paresthesias in the right C8 and T1 dermatomes. MRI demonstrated a T2 hypointense epidural soft tissue mass extending from C6-T1. The patient underwent C6-T1 laminoforaminotomy and partial resection with near complete symptom resolution. Histopathology was consistent with diagnosis of IgG4-RHP. Eighteen months postoperatively, she experienced symptom recurrence necessitating re-operation and adjuvant postoperative prednisone with complete resolution at 40-months' follow-up. Results and Conclusions: Of the now nineteen confirmed cases of IgG4-RHP, fifteen underwent surgery. A majority achieved partial resection. Three surgical patients did not receive adjuvant therapy with symptomatic recurrence between 2 and 18 months.