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1.
World Neurosurg ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992727

ABSTRACT

OBJECTIVE: This study evaluates the impact of L4-5 minimally invasive surgery (MIS)-TLIF on adjacent-level parameters. METHODS: This is a retrospective study performed on consecutive patients between January 2015-December 2019. The index- and adjacent-level segmental lordosis (SL) and disc angle (DA) were measured. Patient-reported outcomes (PROs) were collected preoperatively and at 3-24 months postoperatively. Factors influencing changes in adjacent-level parameters and the occurrence of adjacent segment degeneration (ASDeg) were assessed. RESULTS: One hundred and seventeen adult patients, averaging 65.5 years of age and slight preponderance of female (56.4%), were analyzed. L4-5 SL decreased at 2 years (p<0.05), but L4-5 DA significantly increased at all timepoints (p<0.05). While L3-4 SL and DA significantly decreased at all timepoints (p<0.05), L5-S1 SL decreased at 3 and 12 months (p<0.05) and L5-S1 DA only significantly decreased at 2 years (p<0.05). All PROs improved significantly (p<0.0001). The ASDeg rate was 19.7% at 2.2 years. Cephalad and caudal ASDeg rates were 12.0% and 10.3%, respectively. Eight patients (6.8%) required adjacent-level reoperations, mainly at L3-4 (6 cases). The use of expandable cage significantly reduced the odds of caudal ASDeg (OR 0.15, p=0.037), but had no significant effect on cephalad ASDeg.. CONCLUSIONS: L4-5 MIS-TLIF had a more consistent effect on L3-4 than L5-S1. Although adjacent-level SL and DA decreased over time, their association with ASDeg appears limited, suggesting a multifactorial etiology. L4-5 MIS-TLIF provides demonstrable clinical benefits with lasting PRO improvements and low adjacent-level reoperations.

2.
J Am Soc Nephrol ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771634

ABSTRACT

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.

3.
World Neurosurg ; 186: e577-e583, 2024 06.
Article in English | MEDLINE | ID: mdl-38588790

ABSTRACT

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.


Subject(s)
Laminectomy , Lumbar Vertebrae , Minimally Invasive Surgical Procedures , Postoperative Complications , Spinal Fusion , Spinal Stenosis , Spondylolisthesis , Humans , Spondylolisthesis/surgery , Laminectomy/methods , Spinal Fusion/methods , Spinal Fusion/adverse effects , Female , Male , Spinal Stenosis/surgery , Middle Aged , Lumbar Vertebrae/surgery , Minimally Invasive Surgical Procedures/methods , Retrospective Studies , Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Adult , Treatment Outcome
4.
J Neurosurg Case Lessons ; 7(12)2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38498913

ABSTRACT

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.

5.
World Neurosurg ; 184: 163-164, 2024 04.
Article in English | MEDLINE | ID: mdl-38266991

ABSTRACT

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.


Subject(s)
Radiculopathy , Spinal Cord Neoplasms , Male , Humans , Aged , Constriction, Pathologic/surgery , Laminectomy , Spinal Cord Neoplasms/diagnostic imaging , Spinal Cord Neoplasms/surgery , Radiculopathy/surgery , Decompression
6.
Biomed Eng Online ; 23(1): 12, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38287324

ABSTRACT

BACKGROUND: The escalating impact of diabetes and its complications, including diabetic foot ulcers (DFUs), presents global challenges in quality of life, economics, and resources, affecting around half a billion people. DFU healing is hindered by hyperglycemia-related issues and diverse diabetes-related physiological changes, necessitating ongoing personalized care. Artificial intelligence and clinical research strive to address these challenges by facilitating early detection and efficient treatments despite resource constraints. This study establishes a standardized framework for DFU data collection, introducing a dedicated case report form, a comprehensive dataset named Zivot with patient population clinical feature breakdowns and a baseline for DFU detection using this dataset and a UNet architecture. RESULTS: Following this protocol, we created the Zivot dataset consisting of 269 patients with active DFUs, and about 3700 RGB images and corresponding thermal and depth maps for the DFUs. The effectiveness of collecting a consistent and clean dataset was demonstrated using a bounding box prediction deep learning network that was constructed with EfficientNet as the feature extractor and UNet architecture. The network was trained on the Zivot dataset, and the evaluation metrics showed promising values of 0.79 and 0.86 for F1-score and mAP segmentation metrics. CONCLUSIONS: This work and the Zivot database offer a foundation for further exploration of holistic and multimodal approaches to DFU research.


Subject(s)
Deep Learning , Diabetes Mellitus , Diabetic Foot , Humans , Diabetic Foot/diagnosis , Artificial Intelligence , Metadata , Quality of Life
8.
Comput Biol Med ; 165: 107468, 2023 10.
Article in English | MEDLINE | ID: mdl-37722158

ABSTRACT

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.


Subject(s)
Electroencephalography , Hypoxia-Ischemia, Brain , Infant, Newborn , Humans , Retrospective Studies , Electrodes , Gestational Age
9.
Children (Basel) ; 10(6)2023 May 23.
Article in English | MEDLINE | ID: mdl-37371150

ABSTRACT

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.

10.
J Neurosurg Spine ; : 1-11, 2023 Mar 03.
Article in English | MEDLINE | ID: mdl-36883617

ABSTRACT

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.

11.
Neurosurgery ; 93(2): 373-386, 2023 08 01.
Article in English | MEDLINE | ID: mdl-36861985

ABSTRACT

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.


Subject(s)
Lordosis , Postoperative Complications , Spinal Fusion , Adult , Female , Humans , Male , Cervical Vertebrae/surgery , Lordosis/etiology , Neck , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Spinal Fusion/adverse effects , Treatment Outcome
12.
Sci Data ; 10(1): 129, 2023 03 10.
Article in English | MEDLINE | ID: mdl-36899033

ABSTRACT

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.


Subject(s)
Electroencephalography , Hypoxia-Ischemia, Brain , Humans , Infant , Infant, Newborn , Hypoxia-Ischemia, Brain/diagnosis
13.
Dev Med Child Neurol ; 65(10): 1395-1407, 2023 10.
Article in English | MEDLINE | ID: mdl-36917624

ABSTRACT

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.


Subject(s)
Electroencephalography , Sleep , Infant, Newborn , Child , Infant , Humans , Brain , Parents , Massage
14.
Transplantation ; 107(4): 941-951, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36476994

ABSTRACT

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.


Subject(s)
Kidney Transplantation , Humans , Female , Prospective Studies , Retrospective Studies , Living Donors
15.
Epilepsia ; 64(2): 456-468, 2023 02.
Article in English | MEDLINE | ID: mdl-36398397

ABSTRACT

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.


Subject(s)
Hypoxia-Ischemia, Brain , Infant, Newborn , Humans , Infant , Hypoxia-Ischemia, Brain/complications , Hypoxia-Ischemia, Brain/diagnosis , Electroencephalography , ROC Curve , Lactic Acid , Gestational Age
16.
Pediatr Nephrol ; 38(4): 1115-1126, 2023 04.
Article in English | MEDLINE | ID: mdl-35943576

ABSTRACT

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.


Subject(s)
Glomerulonephritis, Membranous , Glomerulosclerosis, Focal Segmental , Nephrosis, Lipoid , Nephrotic Syndrome , Child , Humans , Nephrosis, Lipoid/drug therapy , Glomerulosclerosis, Focal Segmental/complications , Neptune , Nephrotic Syndrome/drug therapy , Proteinuria/etiology , Glomerulonephritis, Membranous/complications , Receptors, Antigen, T-Cell/therapeutic use , Recurrence
18.
Ann Rev Mar Sci ; 15: 223-248, 2023 01 16.
Article in English | MEDLINE | ID: mdl-35973719

ABSTRACT

The Arctic Ocean's Beaufort Gyre is a dominant feature of the Arctic system, a prominent indicator of climate change, and possibly a control factor for high-latitude climate. The state of knowledge of the wind-driven Beaufort Gyre is reviewed here, including its forcing, relationship to sea-ice cover, source waters, circulation, and energetics. Recent decades have seen pronounced change in all elements of the Beaufort Gyre system. Sea-ice losses have accompanied an intensification of the gyre circulation and increasing heat and freshwater content. Present understanding of these changes is evaluated, and time series of heat and freshwater content are updated to include the most recent observations.


Subject(s)
Ice Cover , Wind , Arctic Regions , Climate Change , Oceans and Seas
19.
Neurosurgery ; 91(5): 764-774, 2022 11 01.
Article in English | MEDLINE | ID: mdl-35951736

ABSTRACT

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.


Subject(s)
Cervical Vertebrae , Spinal Fusion , Benzophenones , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Diskectomy/adverse effects , Humans , Ketones , Polyethylene Glycols , Polymers , Retrospective Studies , Spinal Fusion/adverse effects , Treatment Outcome
20.
Neonatology ; 119(5): 594-601, 2022.
Article in English | MEDLINE | ID: mdl-35896077

ABSTRACT

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.


Subject(s)
Infant, Premature, Diseases , Infant, Premature , Adult , Cardiac Output/physiology , Echocardiography , Female , Fetal Growth Retardation , Humans , Infant , Infant, Newborn , Monitoring, Physiologic , Reproducibility of Results
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