Summary
Sleep‐disordered breathing is an important health issue for children. The objective of this study was to develop a machine learning classifier model for the identification of sleep apnea ...events taken exclusively from nasal air pressure measurements acquired during overnight polysomnography for paediatric patients. A secondary objective of this study was to differentiate site of obstruction exclusively from hypopnea event data using the model. Computer vision classifiers were developed via transfer learning to either normal breathing while asleep, obstructive hypopnea, obstructive apnea or central apnea. A separate model was trained to identify site of obstruction as either adeno‐tonsillar or tongue base. In addition, a survey of board‐certified and board‐eligible sleep physicians was completed to compare clinician versus model classification performance of sleep events, and indicated very good performance of our model relative to human raters. The nasal air pressure sample database available for modelling comprised 417 normal, 266 obstructive hypopnea, 122 obstructive apnea and 131 central apnea events derived from 28 paediatric patients. The four‐way classifier achieved a mean prediction accuracy of 70.0% (95% confidence interval 67.1–72.9). Clinician raters correctly identified sleep events from nasal air pressure tracings 53.8% of the time, whereas the local model was 77.5% accurate. The site of obstruction classifier achieved a mean prediction accuracy of 75.0% (95% confidence interval 68.7–81.3). Machine learning applied to nasal air pressure tracings is feasible and may exceed the diagnostic performance of expert clinicians. Nasal air pressure tracings of obstructive hypopneas may “encode” information regarding the site of obstruction, which may only be discernable by machine learning.
APOL1 variants have been associated with renal phenotypes in blacks. To refine clinical outcomes and discover mechanisms of APOL1-associated kidney injury, we analyzed clinical and genomic datasets ...derived from 90 black subjects in the Nephrotic Syndrome Study Network (NEPTUNE), stratified by APOL1 risk genotype. Ninety subjects with proteinuria ≥0.5 g/d were enrolled at first biopsy for primary nephrotic syndrome and followed. Clinical outcomes were determined, and renal histomorphometry and sequencing of Mendelian nephrotic syndrome genes were performed. APOL1 variants were genotyped, and glomerular and tubulointerstitial transcriptomes from protocol renal biopsy cores were analyzed for differential and correlative gene expression. Analyses were performed under the recessive model (high-risk genotype defined by two risk alleles). APOL1 high-risk genotype was significantly associated with a 17 ml/min per 1.73 m(2) lower eGFR and a 69% reduction in the probability of complete remission at any time, independent of histologic diagnosis. Neither APOL1 risk group was enriched for Mendelian mutations. On renal biopsy, high-risk genotype was associated with increased fractional interstitial area, interstitial fibrosis, and tubular atrophy. Risk genotype was not associated with intrarenal APOL1 mRNA expression levels. Differential expression analysis demonstrated an increased steady-state level of five genes associated with the high-risk genotype (CXCL9, CXCL11, and UBD in glomerulus; SNOR14B and MUC13 in tubulointerstitium). APOL1 tubulointerstitial coexpression analysis showed coexpression of APOL1 mRNA levels with a group of intrarenal transcripts that together were associated with increased interstitial fibrosis and tubular atrophy. These data indicate the high-risk APOL1 genotype confers renal risk across histopathologic diagnoses.
To evaluate transjugular intrahepatic portosystemic shunt (TIPS) outcomes and procedure metrics with the use of three different image guidance techniques for portal vein (PV) access during TIPS ...creation.
A retrospective review of consecutive patients who underwent TIPS procedures for a range of indications during a 28-month study period identified a population of 68 patients. This was stratified by PV access techniques: fluoroscopic guidance with or without portography (n = 26), PV marker wire guidance (n = 18), or intravascular ultrasound (US) guidance (n = 24). Procedural outcomes and procedural metrics, including radiation exposure, contrast agent volume used, procedure duration, and PV access time, were analyzed.
No differences in demographic or procedural characteristics were found among the three groups. Technical success, technical success of the primary planned approach, hemodynamic success, portosystemic gradient, and procedure-related complications were not significantly different among groups. Fluoroscopy time (P = .003), air kerma (P = .01), contrast agent volume (P = .003), and total procedural time (P = .02) were reduced with intravascular US guidance compared with fluoroscopic guidance. Fluoroscopy time (P = .01) and contrast agent volume (P = .02) were reduced with intravascular US guidance compared with marker wire guidance.
Intravascular US guidance of PV access during TIPS creation not only facilitates successful TIPS creation in patients with challenging anatomy, as suggested by previous investigations, but also reduces important procedure metrics including radiation exposure, contrast agent volume, and overall procedure duration compared with fluoroscopically guided TIPS creation.
The Nephrotic Syndrome Study Network (NEPTUNE) is a North American multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This ...includes a longitudinal observational cohort study, a pilot and ancillary study program, a training program, and a patient contact registry. NEPTUNE will enroll 450 adults and children with minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy for detailed clinical, histopathological, and molecular phenotyping at the time of clinically indicated renal biopsy. Initial visits will include an extensive clinical history, physical examination, collection of urine, blood and renal tissue samples, and assessments of quality of life and patient-reported outcomes. Follow-up history, physical measures, urine and blood samples, and questionnaires will be obtained every 4 months in the first year and biannually, thereafter. Molecular profiles and gene expression data will be linked to phenotypic, genetic, and digitalized histological data for comprehensive analyses using systems biology approaches. Analytical strategies were designed to transform descriptive information to mechanistic disease classification for nephrotic syndrome and to identify clinical, histological, and genomic disease predictors. Thus, understanding the complexity of the disease pathogenesis will guide further investigation for targeted therapeutic strategies.
The recent discovery of mutations in the gene encoding diacylglycerol kinase
(DGKE) identified a novel pathophysiologic mechanism leading to HUS and/or MPGN. We report ten new patients from eight ...unrelated kindreds with DGKE nephropathy. We combined these cases with all previously published cases to characterize the phenotypic spectrum and outcomes of this new disease entity. Most patients presented with HUS accompanied by proteinuria, whereas a subset of patients exhibited clinical and histologic patterns of MPGN without TMA. We also report the first two patients with clinical and histologic HUS/MPGN overlap. DGKE-HUS typically manifested in the first year of life but was not exclusively limited to infancy, and viral triggers frequently preceded HUS episodes. We observed signs of complement activation in some patients with DGKE-HUS, but the role of complement activation remains unclear. Most patients developed a slowly progressive proteinuric nephropathy: 80% of patients did not have ESRD within 10 years of diagnosis. Many patients experienced HUS remission without specific treatment, and a few patients experienced HUS recurrence despite complete suppression of the complement pathway. Five patients received renal allografts, with no post-transplant recurrence reported. In conclusion, we did not observe a clear genotype-phenotype correlation in patients with DGKE nephropathy, suggesting additional factors mediating phenotypic heterogeneity. Furthermore, the benefits of anti-complement therapy are questionable but renal transplant may be a feasible option in the treatment of patients with this condition.
Intestinal ischemia-reperfusion (IR) injury is initiated when natural Abs recognize neoantigens that are revealed on ischemic cells. Cr2(-/-) mice, deficient in complement receptors (CR)1 and CR2, ...demonstrate defects in T-dependent B-2 B cell responses to foreign Ags and have also been suggested to manifest abnormalities of the B-1 subset of B lymphocytes. To determine whether these CRs might play a role in the generation of the natural Abs that initiate intestinal IR injury, we performed experiments in Cr2(-/-) and control Cr2(+/+) mice. We found that Cr2(-/-) mice did not demonstrate severe intestinal injury that was readily observed in control Cr2(+/+) mice following IR, despite having identical serum levels of IgM and IgG. Pretreatment of Cr2(-/-) mice before the ischemic phase with IgM and IgG purified from the serum of wild-type C57BL/6 mice reconstituted all key features of IR injury, demonstrating that the defect involves the failure to develop this subset of natural Abs. Pretreatment with IgM and IgG individually demonstrates that each contributes to unique features of IR injury. In sum, CR2/CR1 play an unanticipated but critical role in the development of a subset of the natural Ab repertoire that has particular importance in the pathogenesis of IR injury.
Abstract
Interventional radiologists are often consulted for acute management of hemorrhagic complications in obstetric and gynecologic patients. The aim of this article is to review the common ...indications for vascular embolization in obstetric and gynecologic emergencies, specifically in the setting of primary postpartum hemorrhage, and to discuss the technique and outcomes of endovascular treatment.
Importance Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease (ESKD) across the lifespan. While 10% to 15% of children and 3% of adults who develop ESKD have ...FSGS, it remains uncertain whether the natural history differs in pediatric vs adult patients, and this uncertainty contributes to the exclusion of children and adolescents in clinical trials. Objective To examine whether there are differences in the kidney health outcomes among children, adolescents, and adults with FSGS. Design, Setting, and Participants This cohort study used pooled and parallel analyses, completed July 5, 2022, from 3 complimentary data sources: (1) Nephrotic Syndrome Rare Disease Clinical Research Network (NEPTUNE); (2) FSGS clinical trial (FSGS-CT); and (3) Kidney Research Network (KRN). NEPTUNE is a multicenter US/Canada cohort study; FSGS-CT is a multicenter US/Canada clinical trial; and KRN is a multicenter US electronic health record–based registry from academic and community nephrology practices. NEPTUNE included 166 patients with incident FSGS enrolled at first kidney biopsy; FSGS-CT included 132 patients with steroid-resistant FSGS randomized to cyclosporine vs dexamethasone with mycophenolate; and KRN included 184 patients with prevalent FSGS. Data were collected from November 2004 to October 2019 and analyzed from October 2020 to July 2022. Exposures Age: children (age <13 years) vs adolescents (13-17 years) vs adults (≥18 years). Covariates of interest included sex, disease duration,APOL1genotype, urine protein–to-creatinine ratio, estimated glomerular filtration rate (eGFR), edema, serum albumin, and immunosuppressive therapy. Main Outcomes and Measures ESKD, composite outcome of ESKD or 40% decline in eGFR, and complete and/or partial remission of proteinuria. Results The study included 127 (26%) children, 102 (21%) adolescents, and 253 (52%) adults, including 215 (45%) female participants and 138 (29%) who identified as Black, 98 (20%) who identified as Hispanic, and 275 (57%) who identified as White. Overall, the median time to ESKD was 11.9 years (IQR, 5.2-19.1 years). There was no difference in ESKD risk among children vs adults (hazard ratio HR, 0.67; 95% CI, 0.43-1.03) or adolescents vs adults (HR, 0.85; 95% CI, 0.52-1.36). The median time to the composite end point was 5.7 years (IQR 1.6-15.2 years), with hazard ratio estimates for children vs adults of 1.12 (95% CI, 0.83-1.52) and adolescents vs adults of 1.06 (95% CI, 0.75-1.50). Conclusions and Relevance In this study, the association of FSGS with kidney survival and functional outcomes was comparable at all ages.
A 65-year-old African American man with end-stage renal disease underwent renal transplantation and developed a perigraft lymphocele with an associated progressive increase in serum creatinine 6 ...weeks after surgery, which failed to resolve with percutaneous drainage and surgical therapy. Fluoroscopic and ultrasound-guided percutaneous transperitoneal balloon fenestration with a 22-mm, 2-cm-long balloon catheter resulted in resolution of the lymphocele as shown by ultrasound at 3 and 5 months.
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