Measures Of Clinical Severity Research Articles

The Robison D. Harley, MD Childhood Glaucoma Research Network International Pediatric Glaucoma Registry: The First 872 Cases

PurposeTo report on epidemiologic data from an international, centralized pediatric glaucoma database of 872 patients, focusing on genetic and clinically significant factors. DesignDatabase study utilizing retrospective analysis. Subjects872 children, both female and male, were included in the database. After accounting for database coding errors, data from 865 patients with pediatric glaucoma were analyzed. Number of eyes analyzed fluctuated for each variable. MethodsThe registry is an open access, no charge, REDCap database. Participating clinical centers input data with local Institutional Review Board approval and subsequently have access for research purposes. We retrospectively reviewed 872 patients, comparing demographics, family history, country, disease presentation, and CGRN diagnoses. Analyses for each variable were conducted in SPSS Software v.28.0. Chi-square analyses were performed for nominal data, and ordinal and continuous data were analyzed using Mann-Whitney test, analysis of variance or Kruskal-Wallis tests with multiple comparisons. Main Outcome MeasuresCGRN glaucoma type and markers of clinical severity by country (laterality, cup-to-disc ratio (CTD), corneal diameter, opacification, edema; visual acuity (VA), intraocular pressure (IOP), Haab striae, axial length). Results20 clinical sites from 10 countries entered data. Centers in the USA, India, and Iran input the most data. In the USA, open angle glaucoma following cataract surgery was most common, while in India and Iran it was primary congenital glaucoma neonatal onset. Bilateral disease was more frequent in India and Iran compared to the USA (X2 = 50.6, p<0.001). Clinical measures of severity were typically worse in India compared to the USA. This included increased CTD (X2 = 24.0, p = 0.002), increased corneal diameter (X2 = 8.9, p = 0.01), presence of corneal opacification (X2 = 10.7, p = 0.001), presence of corneal edema (X2 = 11.7, p<0.001), and worse VA (U = 873.5, p<0.001). IOP and presence of Haab striae were not associated with country (p>0.05), while axial length was increased in the USA by an average of 1.04mm (U = 5787, p = 0.002). ConclusionsThis registry has potential to advance our understanding of pediatric glaucoma. Differences in family history, disease presentation, and glaucoma type suggest unique country phenotypes. Registry expansion may allow for insight into best practices for pediatric glaucoma.

Absence of Cerebrospinal Fluid Pleocytosis in Encephalitis.

Early diagnosis of encephalitis involves identifying signs of neuroinflammation, including cerebrospinal fluid (CSF) pleocytosis. However, absence of CSF pleocytosis in encephalitis has been described, most notably in autoimmune encephalitis. We examined clinical characteristics and outcomes associated with the absence or presence of CSF white blood cell pleocytosis (≥ 5 cells/µL), to inform timely diagnosis and management of encephalitis. This retrospective study compares initial CSF profiles in 597 adult patients with all-cause encephalitis. Of the 597 patients, 446 (74.7%) had CSF pleocytosis while 151 (25.3%) did not. CSF pleocytosis occurred more commonly in infectious cases (200/446, 44.8%), along with 59 (13.2%) autoimmune cases, comprised chiefly of anti-NMDAR encephalitis (37/59, 62.7%). Notably, the group without pleocytosis was comprised of similar proportions of infectious (47/151, 31.1%) and autoimmune (38/151, 25.92%; p>0.05) encephalitis. Among those with infectious encephalitis, 47/247 (19%) had absent pleocytosis, including 18/76 (23.7%) with HSV-1 encephalitis. The absence of pleocytosis was associated with a decreased rate of acyclovir administration (47.7% in patients without pleocytosis vs. 71.1% in patients with pleocytosis, p<0.001). Despite pleocytosis being associated with some measures of clinical severity at admission such as a Full Outline of UnResponsiveness (FOUR) score ≤14, it was not associated with mortality or prolonged hospitalization. CSF pleocytosis is an important criterion for encephalitis diagnosis, but 25.3% of patients with all-cause encephalitis and 23.7% of those with HSV-1 encephalitis exhibit absence of pleocytosis on initial LP. Acyclovir initiation should not be delayed in the absence of pleocytosis in patients with suspected encephalitis.

Using Precision Medicine to Disentangle Genotype-Phenotype Relationships in Twins with Rett Syndrome: A Case Report.

Rett syndrome (RTT) is a paediatric neurodevelopmental disorder spanning four developmental stages. This multi-system disorder offers a unique window to explore genotype-phenotype relationships in a disease model. However, genetic prognosticators of RTT have limited clinical value due to the disorder's heterogeneity on multiple levels. This case report used a precision medicine approach to better understand the clinical phenotype of RTT twins with an identical pathogenic MECP2 mutation and discordant neurodevelopmental profiles. Targeted genotyping, objective physiological monitoring of heart rate variability (HRV) parameters, and clinical severity were assessed in a RTT twin pair (5 years 7 months old) with an identical pathogenic MECP2 mutation. Longitudinal assessment of autonomic HRV parameters was conducted using the Empatica E4 wristband device, and clinical severity was assessed using the RTT-anchored Clinical Global Impression Scale (RTT-CGI) and the Multi-System Profile of Symptoms Scale (MPSS). Genotype data revealed impaired BDNF function for twin A when compared to twin B. Twin A also had poorer autonomic health than twin B, as indicated by lower autonomic metrics (autonomic inflexibility). Hospitalisation, RTT-CGI-S, and MPSS subscale scores were used as measures of clinical severity, and these were worse in twin A. Treatment using buspirone shifted twin A from an inflexible to a flexible autonomic profile. This was mirrored in the MPSS scores, which showed a reduction in autonomic and cardiac symptoms following buspirone treatment. Our findings showed that a combination of a co-occurring rs6265 BDNF polymorphism, and worse autonomic and clinical profiles led to a poorer prognosis for twin A compared to twin B. Buspirone was able to shift a rigid autonomic profile to a more flexible one for twin A and thereby prevent cardiac and autonomic symptoms from worsening. The clinical profile for twin A represents a departure from the disorder trajectory typically observed in RTT and underscores the importance of wider genotype profiling and longitudinal objective physiological monitoring alongside measures of clinical symptoms and severity when assessing genotype-phenotype relationships in RTT patients with identical pathogenic mutations. A precision medicine approach that assesses genetic and physiological risk factors can be extended to other neurodevelopmental disorders to monitor risk when genotype-phenotype relationships are not so obvious.

Approach to Mycosis Fungoides in children: Consensus-based recommendations

Pediatric Mycosis fungoides (MF) management extrapolates from adult guidelines, despite differing clinical aspects. Recommendations are essential to address unique challenges in this distinct patient group. This project aims to derive consensus recommendations for pediatric MF management. Experts from pediatric dermatology, general dermatology, dermatopathology, and pediatric hematology-oncology (N=83) were invited to contribute to consensus recommendations. The process involved 3 electronic Delphi rounds, concluding with a final consensus meeting using a modified Nominal Group Technique for unresolved items. Consensus included more clinical severity measures than tumor-node-metastasis-blood staging: pruritus, functional or esthetic impairment (eg, palms, soles, genitalia), quality of life impact, and psychological aspects (eg,embarrassment, anxiety, depression), plus parental anxiety. Ten recommendations were made for managing early and advanced pediatric MF. Disagreement emerged in choosing therapies beyond stage I of the disease. This multinational initiative aimed to standardize optimal pediatric MF management and successfully generated consensus recommendations. Additional work is needed for structured, prospective protocols in advanced-stage pediatric MF. Lack of pediatric hematologists-oncologists and patients' representatives. Documentation of extended clinical severity and outcome measures is recommended. Addressing the need for structured protocols in advanced-stage pediatric MF and implementing systematic, prospective data collection is crucial.

Effect of Micronized Purified Flavonoid Fraction on Venous Hemodynamics Evaluated Using Digital Photoplethysmography in Patients with Chronic Venous Disease

Micronized purified flavonoid fraction (MPFF) is the most widely prescribed and well-studied venoactive drug available for the treatment of chronic venous disease (CVD). Photoplethysmography (PPG) is used to quantitatively measure venous hemodynamics and provide information about the overall function of the venous system. The aim of this study was to use digital PPG to evaluate the effects of MPFF on venous hemodynamics in patients with CVD. Patients diagnosed with CVD at an outpatient clinic in Bursa, Turkey between February 2018 and July 2020 were assessed for inclusion in this retrospective analysis. Patients who complied with the advised treatment strategy (MPFF 1,000mg tablets taken orally once daily and compression garments) and attended follow-up visits were included in the analysis. Digital PPG was used to measure venous refilling time (VRT) and venous pumping capacity (VPC) at diagnosis and 6months of follow-up. The Venous Clinical Severity Score (VCSS) was also obtained at these visits, and patients completed the 20-item Chronic Venous Insufficiency Questionnaire (CIVIQ-20). In total, 721 patients (mean age 52years) with C0-C4 CVD were included in the study. PPG showed that VRT and VPC increased significantly from 19.0sec to 2.0%, respectively, at diagnosis to 27.4 and 4.9%, respectively, at 6months (both P<0.05). Mean VCSS improved significantly from 7.9 at diagnosis to 3.1 at 6months (P<0.05). Mean CIVIQ-20 score also improved significantly at the 6-month follow-up (20.1 vs 38.6 at diagnosis; P<0.01). In patients with C0-C4 CVD, 6months of MPFF treatment plus the wearing of compression garments was associated with statistically significant improvements in venous hemodynamic parameters measured by PPG, as well as measures of clinical severity and quality of life.

Psychometric properties of the KCCQ-12 in an european cohort of patients with heart failure

Abstract Background Despite medical advances, patients with heart failure continue to suffer from poor quality of life due to worsening symptoms and functional limitations. Therefore, it is important to understand the multidimensional facets of quality of life in these patients. The Kansas City Cardiomyopathy Questionnaire is a commonly used quality of life assessment tool worldwide. However, However, there is still a lack of knowledge about its psychometric properties. Purpose The aim of this study was to investigate the psychometric properties of the KCCQ-12 and its measurement invariance in a cohort of European patients with heart failure. Methods Participants (n=510, median age=72, IQR=18, 58% males) completed the KCCQ-12 alongside measures of clinical psychosocial severity. A confirmatory factor analysis was used to establish factorial validity; internal consistency was determined using the Omega coefficient and the model-based internal consistency coefficient. Zero-order correlations between the KCCQ-12 scores and clinical and psychosocial measures were performed to test convergent validity. Multigroup confirmatory factor analysis was conducted to test measurement invariance across patients with preserved vs reduced ejection fraction. Results Confirmatory factor analysis confirmed a four-factor solution, with the domains of physical limitations, symptom frequency, quality of life, and social interference. Internal consistency was excellent (Omega coefficients ranging from 0.83 and 0.90, and internal consistency index of 0.94). The KCCQ-12 scores significantly correlated with ejection fraction, New York Heart Association class, quality of life, anxiety, depression, symptom burden, and the KCCQ-23 Overall Summary score, which adequately supported the convergent validity of the KCCQ-12. Measurement invariance was confirmed at the partial scalar and strict level. Conclusions These findings support the validity and reliability of the KCCQ-12, both in patients with reduced and preserved ejection fraction. Hence, this version can be confidently used both in research and clinical practice to measure quality of life of heart failure patients.

Predictors of alcohol and other drug treatment completion among young people accessing residential and community-based treatment: A retrospective analysis of routinely collected service data.

Young people accessing alcohol and other drug (AOD) treatment experience high rates of treatment disengagement, contributing to poorer outcomes. To improve outcomes, it is important to identify factors associated with treatment retention. This study measured the relationships between client characteristics, treatment characteristics, clinical severity measures and completion of treatment among young people. This study was a retrospective analysis of routinely collected data set in residential- and community-based AOD services in New South Wales, Australia. Routinely collected data from the Network of Alcohol and Other Drug Agencies' (NADA) database were used. Included individuals were aged 10-24 years and accessed treatment between 2012 and 2023 (n = 17 474). Variables included client-related characteristics, service characteristics and baseline measures of clinical severity [Kessler-10 (K10), EUROHIS-QoL, severity of dependence scale (SDS)]. Multivariable binary logistic regression models assessed the relationships between these characteristics and treatment completion. Rates of treatment completion were highest among adolescents in community-based treatment (57%) and lowest among young adults in residential treatment (35%). Polysubstance use was negatively associated with treatment completion among adolescents [adjusted odds ratio (adjOR) = 0.71, P < 0.001] and adults (adjOR = 0.70, P < 0.001) in community-based treatment, and adolescents in residential treatment (adjOR = 0.62, P = 0.006), as was housing insecurity (adolescents in community treatment, adjOR = 0.61, P = 0.001; adults in community treatment, adjOR = 0.77, P = 0.002; adolescents in residential treatment, adjOR = 0.42, P = 0.005). Attending youth-specific services was associated with higher treatment completion rates among adults in community-based (adjOR = 1.81, P < 0.001) and residential treatment (adjOR = 1.72, P < 0.001). Varying correlates of treatment completion were identified throughout treatment groups, reflecting the differences in population and/or needs across contexts. In New South Wales, Australia, fewer than half of young people accessing alcohol and other drug treatment between 2012 and 2023 completed treatment, and completion rates were lower among those facing barriers such as polysubstance use and housing insecurity.

Central involvement in peripheral disease: melanopsin pathway impairment in chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) compromises functions of the peripheral nervous system (PNS). Recently, however, symptoms such as cognitive deficits, visual dysfunction and circadian disorders were reported, compatible with additional involvement of the central nervous system (CNS) in CIDP. Against this background, we were interested in the functional state of melanopsin-expressing retinal ganglion cells (mRGCs) as a potential biomarker for sleep-wake abnormalities and CNS involvement in CIDP. Based on a chromatic pupillometry protocol, we examined the integrity of the melanopsin system in a prospective case-control study in 20 persons with CIDP compared to 20 controls without CIDP. The results were referred to clinical measures of disease severity and sleep behaviour. Patients with CIDP had a significantly reduced melanopsin-mediated post-illumination pupil response (PIPR) compared to healthy controls (25% versus 36%; P < 0.01). This reduction correlated with disease severity (r = 0.478, P < 0.05). Further, patients with CIDP reported diminished sleep quality (P < 0.05); however, there was no significant correlation with the melanopsin-mediated PIPR. The results demonstrate an impairment of mRGC function related to CIDP. Since the PIPR reduction correlated with disease severity, it could be an easily available biomarker for CNS affection in CIDP, a condition defined as PNS disorder.

Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study

ObjectivesTo assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population.MethodsIn this multicentre...

PSYCHOMETRIC PROPERTIES OF THE KCCQ–12 IN A EUROPEAN COHORT OF PATIENTS WITH HEART FAILURE

Abstract Background Despite medical advances, patients with heart failure continue to suffer from poor quality of life due to worsening symptoms and functional limitations. Therefore, it is important to understand the multidimensional facets of quality of life in these patients. The Kansas City Cardiomyopathy Questionnaire is a commonly used quality of life assessment tool worldwide. However, However, there is still a lack of knowledge about its psychometric properties. Purpose The aim of this study was to investigate the psychometric properties of the KCCQ–12 and its measurement invariance in a cohort of European patients with heart failure. Methods Participants (n=510, median age=72, IQR=18, 58% males) completed the KCCQ–12 alongside measures of clinical psychosocial severity. A confirmatory factor analysis was used to establish factorial validity; internal consistency was determined using the Omega coefficient and the model–based internal consistency coefficient. Zero–order correlations between the KCCQ–12 scores and clinical and psychosocial measures were performed to test convergent validity. Multigroup confirmatory factor analysis was conducted to test measurement invariance across patients with preserved vs reduced ejection fraction. Results Confirmatory factor analysis confirmed a four–factor solution, with the domains of physical limitations, symptom frequency, quality of life, and social interference. Internal consistency was excellent (Omega coefficients ranging from 0.83 and 0.90, and internal consistency index of 0.94). The KCCQ–12 scores significantly correlated with ejection fraction, New York Heart Association class, quality of life, anxiety, depression, symptom burden, and the KCCQ–23 Overall Summary score, which adequately supported the convergent validity of the KCCQ–12. Measurement invariance was confirmed at the partial scalar and strict level. Conclusions These findings support the validity and reliability of the KCCQ–12, both in patients with reduced and preserved ejection fraction. Hence, this version can be confidently used both in research and clinical practice to measure quality of life of heart failure patients.

MRI and Blood-based Biomarkers Are Associated With Surgery in Children and Adults With Ileal Crohn's Disease.

Despite advances in medical therapy, many children and adults with ileal Crohn's disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management. This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ± 13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon correctedAkaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13). After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD.

Electroencephalographic Correlates of Clinical Severity in the Natural history study of RTT and Related Disorders.

This study was undertaken to characterize quantitative electroencephalographic (EEG) features in participants from the Natural history study of RTT and Related Disorders and to assess the potential for these features to act as objective measures of cortical function for Rett syndrome (RTT). EEG amplitude and power features were derived from the resting EEG of 60 females with RTT (median age = 10.7 years) and 26 neurotypical females (median age = 10.6 years). Analyses focus on group differences and within the RTT group, associations between the EEG parameters and clinical severity. For a subset of participants (n = 20), follow-up data were available for assessing the reproducibility of the results and the stability in the parameters over 1 year. Compared to neurotypical participants, participants with RTT had greater amplitude variability and greater low-frequency activity as reflected by greater delta power, more negative 1/f slope, and lower theta/delta, alpha/delta, beta/delta, alpha/theta, and beta/theta ratios. Greater delta power, more negative 1/f slope, and lower power ratios were associated with greater severity. Analyses of year 1 data replicated the associations between 1/f slope and power ratios and clinical severity and demonstrated good within-subject consistency in these measures. Overall, group comparisons reflected a greater predominance of lower versus higher frequency activity in participants with RTT, which is consistent with prior clinical interpretations of resting EEG in this population. The observed associations between the EEG power measures and clinical assessments and the repeatability of these measures underscore the potential for EEG to provide an objective measure of cortical function and clinical severity for RTT. ANN NEUROL 2024;96:175-186.

The Child Opportunity Index 2.0 and exacerbation-prone asthma in a cohort of urban children.

Social determinants of health underlie disparities in asthma. However, the effects of individual determinants likely interact, so a summary metric may better capture their impact. The Child Opportunity Index 2.0 (COI) is one such tool, yet its association with exacerbation-prone (EP) asthma is unknown. To investigate the association between the COI and EP asthma and clinical measures of asthma severity in children. We analyzed data from two prospective observational pediatric asthma cohorts (n = 193). Children were classified as EP (≥1 exacerbation in the past 12 months) or exacerbation-null (no exacerbations in the past 5 years). Spirometry, exhaled nitric oxide, IgE, and Composite Asthma Severity Index (CASI) were obtained. The association between COI and EP status was assessed with logistic regression. We fit linear and logistic regression models to test the association between COI and each clinical measure. A 20-point COI decrease conferred 40% higher odds of EP asthma (OR 1.4; 95%CI 1.1-1.76). The effect was similar when adjusted for age and sex (OR 1.38, 95%CI 1.1-1.75) but was attenuated with additional adjustment for race and ethnicity (OR 1.19, 95%CI 0.92-1.54). A similar effect was seen for the Social/Economic and Education COI domains but not the Health/Environment Domain. A 20-point COI decrease was associated with an increase in CASI of 0.34. COI was not associated with other clinical measures. Lower COI was associated with greater odds of EP asthma. This highlights the potential use of the COI to understand neighborhood-level risk and identify community targets to reduce asthma disparities.

Utilizing ultra-early continuous physiologic data to develop automated measures of clinical severity in a traumatic brain injury population

Determination of prognosis in the triage process after traumatic brain injury (TBI) is difficult to achieve. Current severity measures like the Trauma and injury severity score (TRISS) and revised trauma score (RTS) rely on additional information from the Glasgow Coma Scale (GCS) and the Injury Severity Score (ISS) which may be inaccurate or delayed, limiting their usefulness in the rapid triage setting. We hypothesized that machine learning based estimations of GCS and ISS obtained through modeling of continuous vital sign features could be used to rapidly derive an automated RTS and TRISS. We derived variables from electrocardiograms (ECG), photoplethysmography (PPG), and blood pressure using continuous data obtained in the first 15 min of admission to build machine learning models of GCS and ISS (ML-GCS and ML-ISS). We compared the TRISS and RTS using ML-ISS and ML-GCS and its value using the actual ISS and GCS in predicting in-hospital mortality. Models were tested in TBI with systemic injury (head abbreviated injury scale (AIS) ≥ 1), and isolated TBI (head AIS ≥ 1 and other AIS ≤ 1). The area under the receiver operating characteristic curve (AUROC) was used to evaluate model performance. A total of 21,077 cases (2009–2015) were in the training set. 6057 cases from 2016 to 2017 were used for testing, with 472 (7.8%) severe TBI (GCS 3–8), 223 (3.7%) moderate TBI (GCS 9–12), and 5913 (88.5%) mild TBI (GCS 13–15). In the TBI with systemic injury group, ML-TRISS had similar AUROC (0.963) to TRISS (0.965) in predicting mortality. ML-RTS had AUROC (0.823) and RTS had AUROC 0.928. In the isolated TBI group, ML-TRISS had AUROC 0.977, and TRISS had AUROC 0.983. ML-RTS had AUROC 0.790 and RTS had AUROC 0.957. Estimation of ISS and GCS from machine learning based modeling of vital sign features can be utilized to provide accurate assessments of the RTS and TRISS in a population of TBI patients. Automation of these scores could be utilized to enhance triage and resource allocation during the ultra-early phase of resuscitation.

High-flow nasal cannula therapy for infants with bronchiolitis.

Bronchiolitis is a common lower respiratory tract illness, usually of viral aetiology, affecting infants younger than 24 months of age and is the most common cause of hospitalisation of infants. It causes airway inflammation, mucus production and mucous plugging, resulting in airway obstruction. Effective pharmacotherapy is lacking and bronchiolitis is a major cause of morbidity and mortality. Conventional treatment consists of supportive therapy in the form of fluids, supplemental oxygen, and respiratory support. Traditionally, oxygen delivery is as a dry gas at 100% concentration via low-flow nasal prongs. However, the use of heated, humidified, high-flow nasal cannula (HFNC) therapy enables delivery of higher inspired gas flows of an air/oxygen blend, at 2 to 3 L/kg per minute up to 60 L/min in children. It can provide some level of continuous positive airway pressure (CPAP) to improve ventilation in a minimally invasive manner. This may reduce the need for invasive respiratory support, thus potentially lowering costs, with clinical advantages and fewer adverse effects. To assess the effects of HFNC therapy compared with conventional respiratory support in the treatment of infants with bronchiolitis. We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, and Web of Science (from June 2013 to December 2022). In addition, we consulted ongoing trial registers and experts in the field to identify ongoing studies, checked reference lists of relevant articles, and searched for conference abstracts. Date restrictions were imposed such that we only searched for studies published after the original version of this review. We included randomised controlled trials (RCTs) or quasi-RCTs that assessed the effects of HFNC (delivering oxygen or oxygen/room air blend at flow rates greater than 4 L/minute) compared to conventional treatment in infants (< 24 months) with a clinical diagnosis of bronchiolitis. Two review authors independently used a standard template to assess trials for inclusion and extract data on study characteristics, risk of bias elements, and outcomes. We contacted trial authors to request missing data. Outcome measures included the need for invasive respiratory support and time until discharge, clinical severity measures, oxygen saturation, duration of oxygen therapy, and adverse events. In this update we included 15 new RCTs (2794 participants), bringing the total number of RCTs to 16 (2813 participants). Of the 16 studies, 11 compared high-flow to low-flow, and five compared high-flow to CPAP. These studies included infants less than 24 months of age as stated in our selection criteria. There were no significant differences in sex. We found that when comparing high-flow to low-flow oxygen therapy for infants with bronchiolitis there may be a reduction in the total length of hospital stay (mean difference (MD) -0.65 days, 95% confidence interval (CI) -1.23 to -0.06; P < 0.00001, I2 = 89%; 7 studies, 1951 participants; low-certainty evidence). There may also be a reduction in the duration of oxygen therapy (MD -0.59 days, 95% CI -1 to -0.18; P < 0.00001, I2 = 86%; 7 studies, 2132 participants; low-certainty evidence). We also found that there was probably an improvement in respiratory rate at one and 24 hours, and heart rate at one, four to six, and 24 hours in those receiving high-flow oxygen therapy when compared to pre-intervention baselines. There was also probably a reduced risk of treatment escalation in those receiving high-flow when compared to low-flow oxygen therapy (risk ratio (RR) 0.55, 95% CI 0.39 to 0.79; P = 0.001, I2 = 43%; 8 studies, 2215 participants; moderate-certainty evidence). We found no difference in the incidence of adverse events (RR 1.2, 95% CI 0.38 to 3.74; P = 0.76, I2 = 26%; 4 studies, 1789 participants; low-certainty evidence) between the two groups. The lack of comparable outcomes in studies comparing high-flow and CPAP, as well as the small numbers of participants, limited our ability to perform meta-analysis on this group. High-flow nasal cannula therapy may have some benefits over low-flow oxygen for infants with bronchiolitis in terms of a greater improvement in respiratory and heart rates, as well as a modest reduction in the length of hospital stay and duration of oxygen therapy, with a reduced incidence of treatment escalation. There does not appear to be a difference in the number of adverse events. Further studies comparing high-flow nasal cannula therapy and CPAP are required to demonstrate the efficacy of one modality over the other. A standardised clinical definition of bronchiolitis, as well as the use of a validated clinical severity score, would allow for greater and more accurate comparison between studies.

Neurofilaments Light Chain in Neurodegenerative Dementias: A Review of Imaging Correlates.

Neurofilaments light chain (NfLs) are currently recognized as a marker of axonal injury and degeneration. Their measurement in biological fluids has a promising role in the diagnosis, prognosis, and monitoring of the therapeutic response in neurological diseases, including neurodegenerative dementias. In recent years, their relationship with clinical phenotypes and measures of disease severity has been extensively studied. Here, we reviewed studies investigating the association between NfLs and imaging measures of grey matter (GM) and white matter (WM) damage in neurodegenerative dementias. We identified a large number of studies investigating this association in Alzheimer's disease (AD) and disorders of the frontotemporal dementia (FTD) spectrum. Results were heterogeneous, possibly due to different methodological approaches-both in NfL measurements and imaging analyses-and inclusion criteria. However, a positive association between NfL levels and GM atrophy, WM microstructural disruption, glucose hypometabolism, and protein accumulation emerged invariably, confirming the role of NfLs as a reliable biomarker for neurodegenerative dementias, albeit not specific.

Gait abnormalities in older adults with transthyretin cardiac amyloidosis

Background Transthyretin cardiac amyloidosis (ATTR cardiac amyloidosis) is caused by variant (ATTRv) or wild type (ATTRwt) transthyretin. While gait abnormalities have been studied in younger patients with ATTRv amyloidosis, research on gait in older adults with ATTR cardiac amyloidosis is lacking. Given ATTR cardiac amyloidosis’ association with neuropathy and orthopedic manifestations, we explore the gait in this population. Methods Twenty-eight older male ATTR cardiac amyloidosis patients and 11 healthy older male controls walked overground with and without a dual cognitive task. Gait parameters: stride width, length, velocity and stance time percentage were measured using an instrumented mat. ATTR amyloidosis patients were further categorized based on clinical and functional assessments. Results We found significant gait differences between ATTR cardiac amyloidosis patients and healthy controls; patients had more variable, slower, narrower and shorter strides, with their feet spending more time in contact with the ground as opposed to in swing. However, the observed gait differences did not correlate with clinical and functional measures of ATTR cardiac amyloidosis severity. Conclusions Our results suggest that gait analysis could be a complementary tool for characterizing ATTR cardiac amyloidosis patients and may inform clinical care as it relates to falls, management of anticoagulation, and functional independence.

Weight Loss for Patients With Gout and Concomitant Obesity: A Proof-of-Concept Randomized Trial.

Despite scarce evidence, guidelines recommend weight loss as a management strategy for patients with gout. We investigated the effect of an intensive dietary intervention on body weight and clinical measures of gout severity in individuals with obesity and gout. We conducted a 16-week randomized nonmasked parallel-group trial in Denmark, randomly assigning (one-to-one) individuals with obesity and gout to a low-energy diet or a control diet. The primary outcome was change in body weight. Key secondary outcomes were changes in serum urate (SU) level and visual analog scale-assessed pain and fatigue. Between December 1, 2018, and June 1, 2019, 61 participants were included in the intention-to-treat population and randomly assigned to the intensive diet group (n=29) or control diet group (n=32). Participants had a mean age of 60.3 (SD 9.9) years and mean body mass index of 35.6 (SD 5.0), and 59 (97%) were men. After 16 weeks, there was a significant difference in change in body weight between the diet and control groups (-15.4 vs -7.7 kg; difference -7.7 kg [95% confidence interval -10.7 to -4.7], P < 0.001). Despite results being potentially in favor of a low-energy diet, we could not confirm differences in SU level changes and fatigue between groups. No differences in pain and gout flares were observed between groups. No serious adverse events or deaths occurred during the trial. An intensive dietary intervention was safe and effectively lowered body weight in people with obesity and gout, but the weight loss did not directly translate into effects on SU level, fatigue, and pain.

Weight suppression at lowest weight as an indicator of eating disorder clinical severity: A retrospective cohort study

ObjectivesWeight suppression (WS) defines the difference between the highest weight in adulthood and the current weight. WS at lowest weight is the difference between the highest and the lowest ever weight. Weight rebound is the difference between the past lowest weight and current weight. The distinction in the capacities of WS, weight rebound, and WS at the lowest weight remains unclear regarding their efficacy in forecasting clinical endpoints. This study assessed the relationship between WS, WS at lowest weight and/or weight rebound and eating disorder (ED) clinical severity. MethodsIn this retrospective cohort study, adult participants were selected at the Outpatient Unit for multidisciplinary assessment of ED, Montpellier, France, between February 2012 and October 2014 and May 2017 and January 2020. ED clinical severity was evaluated using the Eating Disorder Examination Questionnaire (EDE-Q). ResultsThe sample included 303 patients: 204 with anorexia nervosa (AN) and 99 with bulimia nervosa (BN). The EDE-Q total score was positively correlated with WS at lowest weight in patients with AN (Spearman's rho = 0.181, p = 0.015) and with BN (Spearman's rho = 0.377; p < 0.001). It was also positively correlated with weight rebound (Spearman's rho = 0.319; p = 0.003) in patients with BN. In the multivariate analysis, EDE-Q total score was associated with WS at lowest weight only in patients with BN (β = 0.265; p = 0.03). ConclusionWS at lowest weight seems to be a good measure of ED clinical severity. More research is needed for better understanding WS at lowest weight in assessment and treatment of patients with ED.

MRI AND BLOOD-BASED BIOMARKERS ASSOCIATED WITH SURGICAL MANAGEMENT IN CHILDREN AND ADULTS WITH SMALL BOWEL CROHN'S DISEASE

Abstract BACKGROUND Despite advances in medical therapy, many children and adults with ileal Crohn’s Disease (CD) progress to fibrostenosis requiring surgery. Prior studies have identified circulating and imaging biomarkers associated with strictures, although their associations with need for surgery are not well-established. PURPOSE We aimed to identify MRI and circulating biomarkers associated with the need for surgical management in chidlren and adults with ileal CD. METHODS This prospective, multi-center study included pediatric and adult CD cases undergoing ileal resection (n=50), and CD controls receiving medical therapy (n=83). Noncontrast research MRI examinations measured bowel wall three-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA) (Figure 1). Circulating biomarkers included CD64, ECM1, and GM-CSF autoantibodies (Ab). Clinical variables, including demographics, anthropometrics, and routine clinical laboratory data (e.g., CRP, fecal calprotectin), also were obtained at the research visit. Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. RESULTS Mean participant age was 23.9±13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR]=2.87; p=0.0009), normalized 3D MTR (OR=1.05; p=0.002), log MOLLI T1 (OR=0.01; p=0.02), log IVIM perfusion fraction (f) (OR=0.38; p=0.04), and IVIM apparent diffusion coefficient (ADC) (OR=0.3; p=0.001). MRI and circulating biomarker Tukey box plots are presented in Figure 2. The multivariable model for surgery based upon AICc criteria included age (OR=1.03; p=0.29), BMI (OR=0.91; p=0.09), log GM-CSF Ab (OR=3.37; p=0.01), normalized 3D MTR (OR=1.07; p=0.007), sMaRIA (OR=1.14; p=0.61), luminal narrowing (OR=10.19; p=0.003), log CRP (normalized) (OR=2.75; p=0.10), and hematocrit (OR=0.90; p=0.13). CONCLUSION After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with need for surgery in ileal CD. GM-CSF autoantibodies and MRI biomarker sequences may be useful for guiding management decisions in CD patients. Figure 1 Research MRI images from a surgical Crohn’s disease patient with stricturing behavior involving the terminal ileum. A and B. Coronal and axial fat-saturated T2-weighted single-shot fast spin-echo (SSFSE) images show wall thickening and luminal narrowing of the terminal ileum (arrows) with more proximal bowel dilation measuring greater than 3 cm. C. Axial 3D magnetization transfer images – MT pulse on (bottom image, arrow), MT pulse off (top image, arrow). D. Axial modified Look-Locker inversion recovery (MOLLI) T1 relaxation image (arrow). E. Representative axial intravoxel incoherent motion diffusion-weighted images with increasing b-values (left to right, arrows). Figure 2 Variation in circulating and imaging biomarkers in Crohn’s disease patients with medical and surgical management. Ctrl: non-IBD healthy controls; Med: CD patients with nonsurgical medical management; Surg: CD patients with surgical management.