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BMJ Open Diabetes Research & Care Jan 2024Diabetic retinopathy (DR) is a leading cause of preventable blindness among working-age adults, primarily driven by ocular microvascular complications from chronic...
INTRODUCTION
Diabetic retinopathy (DR) is a leading cause of preventable blindness among working-age adults, primarily driven by ocular microvascular complications from chronic hyperglycemia. Comprehending the complex relationship between microvascular changes in the eye and disease progression poses challenges, traditional methods assuming linear or logistical relationships may not adequately capture the intricate interactions between these changes and disease advances. Hence, the aim of this study was to evaluate the microvascular involvement of diabetes mellitus (DM) and non-proliferative DR with the implementation of non-parametric machine learning methods.
RESEARCH DESIGN AND METHODS
We conducted a retrospective cohort study that included optical coherence tomography angiography (OCTA) images collected from a healthy group (196 eyes), a DM no DR group (120 eyes), a mild DR group (71 eyes), and a moderate DR group (66 eyes). We implemented a non-parametric machine learning method for four classification tasks that used parameters extracted from the OCTA images as predictors: DM no DR versus healthy, mild DR versus DM no DR, moderate DR versus mild DR, and any DR versus no DR. SHapley Additive exPlanations values were used to determine the importance of these parameters in the classification.
RESULTS
We found large choriocapillaris flow deficits were the most important for healthy versus DM no DR, and became less important in eyes with mild or moderate DR. The superficial microvasculature was important for the healthy versus DM no DR and mild DR versus moderate DR tasks, but not for the DM no DR versus mild DR task-the stage when deep microvasculature plays an important role. Foveal avascular zone metric was in general less affected, but its involvement increased with worsening DR.
CONCLUSIONS
The findings from this study provide valuable insights into the microvascular involvement of DM and DR, facilitating the development of early detection methods and intervention strategies.
Topics: Adult; Humans; Diabetic Retinopathy; Retrospective Studies; Retinal Vessels; Tomography, Optical Coherence; Microvessels; Diabetes Mellitus
PubMed: 38167606
DOI: 10.1136/bmjdrc-2023-003758 -
BMC Medical Genomics Jun 2024Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by biallelic variants in the N-acetylgalactosamine-6-sulfatase (GALNS) gene and is...
BACKGROUND
Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by biallelic variants in the N-acetylgalactosamine-6-sulfatase (GALNS) gene and is characterized by progressive and multi-system involvements, dominantly with skeletal deformities. A mild form of MPS IVA often presents with atypical symptoms and can go unrecognized for years.
METHODS
The diagnosis of MPS IVA was confirmed via GALNS enzyme activity testing in leukocytes. Clinical features were collected. Molecular analysis was performed by next generation sequence and Sanger sequencing of the GALNS gene. The pathogenicity of the deep intron variant was verified by mRNA analyses.
RESULTS
Thirteen patients with mild MPS IVA from six families were included. All probands first visit pediatric orthopedists and it took 5.6 years to be diagnosed after the disease onset. The most common symptoms in our series were waddling gait (85%), short neck (69%) and flat feet (62%). Radiologic findings indicated skeletal abnormalities in all patients, especially modification of the vertebral bodies (100%) and acetabular and femoral head dysplasia (100%). Five novel GALNS variants, including c.121-2_121-1insTTTGCTGGCATATGCA, E2 deletion, c.569 A > G, c.898 + 2 T > A, and c.1139 + 2 T > C, were identified. The most common variant, a deep intron variant NM_000512.5: c.121-210 C > T (NM_001323544.2: c.129 C > T, p.G43G), was revealed to result in an 11 bp deletion (c.128_138delGCGATGCTGAG, p.Gly43Aspfs*5) on GALNS mRNA in the GALNS transcript of NM_001323544.2.
CONCLUSIONS
This study provides significant insights into the clinical features and molecular characteristics that contribute to the early diagnosis of mild MPS IVA. On the basis of our cohort, orthopedists need to be able to recognize signs and symptoms of mild MPS IVA as well as the molecular and biochemical diagnosis so that an early diagnosis and treatment can be instituted.
Topics: Humans; Male; Mucopolysaccharidosis IV; Child; Female; Delayed Diagnosis; Child, Preschool; Adolescent; Chondroitinsulfatases; Mutation
PubMed: 38831290
DOI: 10.1186/s12920-024-01910-x -
The Journal of Maternal-fetal &... Dec 2023Prenatal diagnosis and counseling of isolated ventriculomegaly (VM) represent a considerable challenge. We aimed to analyze the intrauterine evolution, associated...
INTRODUCTION
Prenatal diagnosis and counseling of isolated ventriculomegaly (VM) represent a considerable challenge. We aimed to analyze the intrauterine evolution, associated anomalies, and neurodevelopmental outcome using the Battelle Development Inventory (BDI) of fetuses with an initial diagnosis of isolated mild VM.
MATERIAL AND METHODS
Retrospective cohort study of fetuses diagnosed with mild isolated VM (10 -12 mm) between 2012 and 2016 in a tertiary hospital. In 2018, parents were invited to complete the structured BDI test for the neurodevelopmental evaluation of their children in five domains (personal-social skills, adaptive behavior, psychomotor ability, communication, and cognition). Results exceeding two standard deviations were considered abnormal and referred to an expert neuropediatrician.
RESULTS
We identified 43 cases of mild isolated VM. In 5 (11%), structural abnormalities were detected during prenatal follow-up, being related to non-regressive forms ( = .01) and bilateral VM ( = .04). The BDI test was completed by 19/43 (44%). The global score was abnormal in 10/19 (53%). Of them, the neuropediatrician confirmed a neurodevelopmental delay solely in 3 cases that had already been diagnosed with neurological disorders. The most affected domains were gross motor skills (63%), personal-social (63%), and adaptive domains (47%). Communicative and cognitive areas were abnormal in 26% of cases.
CONCLUSION
In fetuses with isolated mild VM detected in the second half of pregnancy, 53% had an abnormal BDI test at 2-6 years, but a neurological disorder was only confirmed in the 30% of them.
Topics: Pregnancy; Child; Female; Humans; Retrospective Studies; Ultrasonography, Prenatal; Hydrocephalus; Prenatal Diagnosis; Fetus; Nervous System Malformations; Pregnancy Outcome; Magnetic Resonance Imaging
PubMed: 37217456
DOI: 10.1080/14767058.2023.2214836 -
Frontiers in Neurology 2023gene pathogenic variations cause a spectrum of phenotypes, ranging from severe Duchenne muscular dystrophy, the Becker milder cases, the intermediate or very mild... (Review)
Review
deletions underlining mild dystrophinopathies: literature review highlights phenotype-related mutation clusters and provides insights about genetic mechanisms and prognosis.
gene pathogenic variations cause a spectrum of phenotypes, ranging from severe Duchenne muscular dystrophy, the Becker milder cases, the intermediate or very mild muscle phenotypes invariably characterized by high CK, and the ultrarare fully-asymptomatic cases. Besides these phenotypes, X-linked dilated cardiomyopathy is also caused by mutations. Males carrying deletions with absent or very mild phenotypes have been sparsely described. We performed a horizon scan on public datasets to enroll males with the above phenotypes and carrying deletions to delineate myopathic genotype-phenotype relationships. We inventoried 81 males, who were divided into the following clinical categorization: fully-asymptomatic males aged >43 years (A, = 22); isolated hyperCKemia (CK, = 35); and mild weakness (any age) with or without high CK (WCK, = 24). In all cases, deleted intervals were exons 2 to 55, and no downstream exons were ever involved, apart from an exon 78 deletion in a WCK patient. All deletions were in-frame apart from the known exception to the rule of exon 2 and exon 78. We correlated the mild phenotypes (A and CK) to deleted exons, intronic breakpoints, exon-exon junctions, 3' isoforms rule, and protein epitopes, and we found that some genetic profiles are exclusively/mainly occurring in A/CK phenotypes, suggesting they are compatible with a -normal muscular performance. We discussed diverse pathogenic mechanisms that may contribute to mild dystrophinopathic phenotypes, and we tried to address some "critical" genetic configurations or exon content needed to preserve a semi-functional gene.
PubMed: 38288333
DOI: 10.3389/fneur.2023.1288721 -
Neural Regeneration Research Jul 2024Patients with mild traumatic brain injury have a diverse clinical presentation, and the underlying pathophysiology remains poorly understood. Magnetic resonance imaging...
Patients with mild traumatic brain injury have a diverse clinical presentation, and the underlying pathophysiology remains poorly understood. Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neurobiological markers after mild traumatic brain injury. This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury. Graph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function. However, most previous mild traumatic brain injury studies using graph theory have focused on specific populations, with limited exploration of simultaneous abnormalities in structural and functional connectivity. Given that mild traumatic brain injury is the most common type of traumatic brain injury encountered in clinical practice, further investigation of the patient characteristics and evolution of structural and functional connectivity is critical. In the present study, we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury. In this longitudinal study, we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 weeks of injury, as well as 36 healthy controls. Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis. In the acute phase, patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network. More than 3 months of follow-up data revealed signs of recovery in structural and functional connectivity, as well as cognitive function, in 22 out of the 46 patients. Furthermore, better cognitive function was associated with more efficient networks. Finally, our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal changes in connectivity in patients with mild traumatic brain injury. These findings highlight the importance of integrating structural and functional connectivity in understanding the occurrence and evolution of mild traumatic brain injury. Additionally, exploratory analysis based on subnetworks could serve a predictive function in the prognosis of patients with mild traumatic brain injury.
PubMed: 38051899
DOI: 10.4103/1673-5374.387971 -
Current Therapeutic Research, Clinical... 2023There are published suggestions that bacterial keratitis (BK) can be classified as mild, moderate, or severe and that the day-1 antibiotic drop regimen may differ for... (Review)
Review
A Review of the Categorizations of Mild, Moderate, and Severe Bacterial Keratitis Ulcers and Day-1 Treatment Regimen When Using the Topical Fluoroquinolones 0.3% Ciprofloxacin and 0.3% Ofloxacin.
BACKGROUND
There are published suggestions that bacterial keratitis (BK) can be classified as mild, moderate, or severe and that the day-1 antibiotic drop regimen may differ for each category using the topical second-generation fluoroquinolones 0.3% ciprofloxacin and 0.3% ofloxacin (2FQ). The classification criteria are not consistently defined and the suggested regimens are often unreferenced and so here, the evidence base for applying such regimens in clinical practice is examined.
OBJECTIVE
To examine the evidence base regarding the categorization criteria used for BK and determine whether any evidence exists to support suggestions that different day-1 treatment regimen using the 2FQ may be applied based on any assigned categorization.
METHODS
The literature on BK treatment was reviewed, as were the clinical studies involving the commercially available 2FQ. All statements pertaining to classification and treatment paradigms involving BK were then collated and reviewed, as were the methodologies employed in the 2FQ clinical studies.
RESULTS
There have been no clinical trials using the 2FQ, or indeed any other topical antibiotics, which have used different day-1 drop regimen depending on the size, depth, and location of the ulcer or for ulcers classified as mild, moderate, or severe. Thus, there is no evidence to support the suggestion that a lower number of drops on day 1 is as effective as a higher number on categorized BK ulcers.
CONCLUSIONS
No standardized method of categorizing BK was found, and there is no evidence to support the contention that mild, moderate, or smaller BK ulcers should be treated any differently to larger or severe ulcers on day 1. The manufacturers of 2FQ do not supply different treatment regimens for different ulcer sizes and severity categories. When using the 2FQ, all BK ulcers should be treated equally in line with the manufacturers' recommended day-1 treatment regimen.
PubMed: 38090721
DOI: 10.1016/j.curtheres.2023.100729 -
Frontiers in Cardiovascular Medicine 2023To compare cardiac function indicators between mild and moderate to severe COVID-19 patients and to try to identify the sequence and directivity in cardiac muscle injury...
OBJECTIVE
To compare cardiac function indicators between mild and moderate to severe COVID-19 patients and to try to identify the sequence and directivity in cardiac muscle injury of COVID-19 patients.
METHODS
From December 2022 to January 2023, all patients with laboratory-confirmed SARS-CoV-2 infection in Shanghai General Hospital Jiading Branch were enrolled. The clinical classification was stratified into mild, moderate, or severe groups. We collected the clinical and laboratory information, transthoracic echocardiographic and speckle-tracking echocardiographic parameters of patients and compared the differences among different groups.
RESULTS
The values of echocardiographic parameters in mild group were lower than that in moderate or severe group ( < 0.05) except LVEF. The values of LVEF of mild and moderate group were higher than severe group ( < 0.05). There were no significant differences between moderate and severe group. Positive correlations were observed between left ventricular global longitudinal strain (LVGLS) and myoglobin ( = 0.72), E/e' and age ( = 0.79), E/e' and BNP ( = 0.67). The multivariate analysis shows that SpO (OR = 0.360, = 0.02), LVGLS (OR = 3.196, = 0.003) and E/e' (OR = 1.307, = 0.036) were the independent risk factors for mild cases progressing to moderate or severe. According to the receiver operating characteristic (ROC) curves, when all the COVID-19 patients was taken as the sample size, the area under the curve (AUC) of the LVGLS was the highest (AUC = 0.861). The AUC of the LVGLS was higher than LVGCS (AUC = 0.565, < 0.001).
CONCLUSION
When mild COVID-19 progresses to moderate or severe, both systolic and diastolic functions of the heart are impaired. LVGLS was the independent risk factor for mild cases progressing to moderate or severe cases. Longitudinal changes may manifest earlier than circumferential changes as myocardial disease progresses in COVID-19.
PubMed: 37908504
DOI: 10.3389/fcvm.2023.1260971 -
Investigative Ophthalmology & Visual... Aug 2023The purpose of this study was to test the hypothesis that retinopathy of prematurity (ROP) prolongs development of rod-mediated thresholds for detection of stimuli at...
PURPOSE
The purpose of this study was to test the hypothesis that retinopathy of prematurity (ROP) prolongs development of rod-mediated thresholds for detection of stimuli at 10 degrees but not 30 degrees eccentricity. In addition, to evaluate the thresholds at each site for an association with visual acuity (VA) and spherical equivalent (SE).
METHODS
We estimated rod-mediated dark-adapted thresholds (DATs) for the detection of 2 degree diameter, 50 ms, blue (λ < 510 nm) flashes at 10 degrees and 30 degrees eccentric in former preterm subjects (n = 111), stratified by ROP severity: None (n = 32), Mild (n = 66), and Severe (n = 13). We also tested Term-born (n = 28) controls. To determine the age at half-maximal sensitivity (Agehalf) for each group and eccentricity, we fit DATs to logistic growth curves. We obtained VA and SE for Preterm subjects and evaluated the course of threshold development at 10 degrees and 30 degrees for significant association with VA and SE predicted at age 10 years.
RESULTS
DAT development at 10 degrees was significantly delayed in ROP (Mild and Severe); ROP did not significantly alter DAT development at 30 degrees. At age 10 years, among Preterm subjects, both VA and SE were significantly associated with group (None,Mild, and Severe). SE was predicted by the course of DAT development at 30 degrees. VA was not associated with the course of DAT development at 10 degrees.
CONCLUSIONS
At 10 degrees, ROP-whether mild or severe-is associated with significant delays in DAT development, evidence that the late-maturing central retina is vulnerable to ROP. The association of 30 degree threshold and myopia are evidence that more peripheral retina is important to refractive development.
Topics: Infant, Newborn; Child; Humans; Retinopathy of Prematurity; Retina; Refractive Errors; Refraction, Ocular; Visual Acuity
PubMed: 37651111
DOI: 10.1167/iovs.64.11.35 -
Pulmonology Oct 2023It is unclear whether patients with Global Initiative for Chronic Obstructive Lung Disease stage 1 (mild) chronic obstructive pulmonary disease (COPD) have worse...
BACKGROUND
It is unclear whether patients with Global Initiative for Chronic Obstructive Lung Disease stage 1 (mild) chronic obstructive pulmonary disease (COPD) have worse respiratory outcomes than individuals with normal spirometry.
METHODS
For this systematic review and meta-analysis, we conducted a search of PubMed, Embase, and Web of Science for all literature published up to 1 March 2023. Studies comparing mortality between mild COPD and normal spirometry were included. A random-effects model was used to estimate the combined effect size and its 95% confidence interval (CI). The primary outcome was all-cause mortality. Respiratory disease-related mortality were examined as secondary outcomes.
RESULTS
Of 5242 titles identified, 12 publications were included. Patients with mild COPD had a higher risk of all-cause mortality than individuals with normal spirometry (pre-bronchodilator: hazard ratio [HR] = 1.21, 95% CI: 1.11-1.32, I = 47.1%; post-bronchodilator: HR = 1.19, 95% CI: 1.02-1.39, I = 0.0%). Funnel plots showed a symmetrical distribution of studies and did not suggest publication bias. In jackknife sensitivity analyses, the increased risk of all-cause mortality remained consistent for mild COPD. When the meta-analysis was repeated and one study was omitted each time, the HR and corresponding 95% CI were >1. Patients with mild COPD also had a higher risk of respiratory disease-related mortality (HR = 1.71, 95% CI: 1.03-2.82, I = 0.0%).
CONCLUSIONS
Our results suggest that mild COPD is associated with increased all-cause mortality and respiratory disease-related mortality compared with normal spirometry. Further research is required to determine whether early intervention and treatment are beneficial in mild COPD.
PubMed: 38093693
DOI: 10.1016/j.pulmoe.2023.09.002 -
Alzheimer's Research & Therapy Jan 2024Mild behavioral impairment (MBI) has been commonly reported in early Alzheimer's disease (AD) but rarely using biomarker-defined samples. It is also unclear whether...
BACKGROUND
Mild behavioral impairment (MBI) has been commonly reported in early Alzheimer's disease (AD) but rarely using biomarker-defined samples. It is also unclear whether genetic polymorphisms influence MBI in such individuals. We thus aimed to examine the association between the cognitive status of participants (amnestic mild cognitive impairment (aMCI-AD) vs cognitively normal (CN) older adults) and MBI severity. Within aMCI-AD, we further examined the association between APOE and BDNF risk genetic polymorphisms and MBI severity.
METHODS
We included 62 aMCI-AD participants and 50 CN older adults from the Czech Brain Aging Study. The participants underwent neurological, comprehensive neuropsychological examination, APOE and BDNF genotyping, and magnetic resonance imaging. MBI was diagnosed with the Mild Behavioral Impairment Checklist (MBI-C), and the diagnosis was based on the MBI-C total score ≥ 7. Additionally, self-report instruments for anxiety (the Beck Anxiety Inventory) and depressive symptoms (the Geriatric Depression Scale-15) were administered. The participants were stratified based on the presence of at least one risk allele in genes for APOE (i.e., e4 carriers and non-carriers) and BDNF (i.e., Met carriers and non-carriers). We used linear regressions to examine the associations.
RESULTS
MBI was present in 48.4% of the aMCI-AD individuals. Compared to the CN, aMCI-AD was associated with more affective, apathy, and impulse dyscontrol but not social inappropriateness or psychotic symptoms. Furthermore, aMCI-AD was related to more depressive but not anxiety symptoms on self-report measures. Within the aMCI-AD, there were no associations between APOE e4 and BDNF Met and MBI-C severity. However, a positive association between Met carriership and self-reported anxiety appeared.
CONCLUSIONS
MBI is frequent in aMCI-AD and related to more severe affective, apathy, and impulse dyscontrol symptoms. APOE and BDNF polymorphisms were not associated with MBI severity separately; however, their combined effect warrants further investigation.
Topics: Humans; Aged; Brain-Derived Neurotrophic Factor; Alzheimer Disease; Genotype; Cognitive Dysfunction; Polymorphism, Genetic; Neuropsychological Tests; Apolipoproteins E
PubMed: 38279143
DOI: 10.1186/s13195-024-01386-y