-
Vascular Medicine (London, England) Jun 2024Systemic vascular involvement in children with cerebral arteriopathies is increasingly recognized and often highly morbid. Fibromuscular dysplasia (FMD) represents a... (Review)
Review
Systemic vascular involvement in children with cerebral arteriopathies is increasingly recognized and often highly morbid. Fibromuscular dysplasia (FMD) represents a cerebral arteriopathy with systemic involvement, commonly affecting the renal and carotid arteries. In adults, FMD diagnosis and classification typically relies on angiographic features, like the 'string-of-beads' appearance, following exclusion of other diseases. Pediatric FMD (pFMD) is considered equivalent to adult FMD although robust evidence for similarities is lacking. We conducted a comprehensive literature review on pFMD and revealed inherent differences between pediatric and adult-onset FMD across various domains including epidemiology, natural history, histopathophysiology, clinical, and radiological features. Although focal arterial lesions are often described in children with FMD, the radiological appearance of 'string-of-beads' is highly nonspecific in children. Furthermore, children predominantly exhibit intimal-type fibroplasia, common in other childhood monogenic arteriopathies. Our findings lend support to the notion that pFMD broadly reflects an undefined heterogenous group of monogenic systemic medium-or-large vessel steno-occlusive arteriopathies rather than a single entity. Recognizing the challenges in categorizing complex morphologies of cerebral arteriopathy using current classifications, we propose a novel term for describing children with cerebral and systemic vascular involvement: 'cerebral and systemic arteriopathy of childhood' (CSA-c). This term aims to streamline patient categorization and, when coupled with advanced vascular imaging and high-throughput genomics, will enhance our comprehension of etiology, and accelerate mechanism-targeted therapeutic developments. Lastly, in light of the high morbidity in children with cerebral and systemic arteriopathies, we suggest that investigating for systemic vascular involvement is important in children with cerebral arteriopathies.
Topics: Humans; Fibromuscular Dysplasia; Child; Risk Factors; Adolescent; Stroke; Child, Preschool; Cerebral Arterial Diseases; Female; Prognosis; Male; Age of Onset; Infant; Predictive Value of Tests; Terminology as Topic; Cerebral Angiography
PubMed: 38898630
DOI: 10.1177/1358863X241254796 -
Nature Communications Jun 2024Mutations in the FOXF1 gene, a key transcriptional regulator of pulmonary vascular development, cause Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins,...
Mutations in the FOXF1 gene, a key transcriptional regulator of pulmonary vascular development, cause Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins, a lethal lung disease affecting newborns and infants. Identification of new FOXF1 upstream regulatory elements is critical to explain why frequent non-coding FOXF1 deletions are linked to the disease. Herein, we use multiome single-nuclei RNA and ATAC sequencing of mouse and human patient lungs to identify four conserved endothelial and mesenchymal FOXF1 enhancers. We demonstrate that endothelial FOXF1 enhancers are autoactivated, whereas mesenchymal FOXF1 enhancers are regulated by EBF1 and GLI1. The cell-specificity of FOXF1 enhancers is validated by disrupting these enhancers in mouse embryonic stem cells using CRISPR/Cpf1 genome editing followed by lineage-tracing of mutant embryonic stem cells in mouse embryos using blastocyst complementation. This study resolves an important clinical question why frequent non-coding FOXF1 deletions that interfere with endothelial and mesenchymal enhancers can lead to the disease.
Topics: Forkhead Transcription Factors; Animals; Humans; Persistent Fetal Circulation Syndrome; Mice; Enhancer Elements, Genetic; Mesoderm; Lung; Endothelial Cells; Zinc Finger Protein GLI1; Embryonic Stem Cells; Pulmonary Alveoli
PubMed: 38898031
DOI: 10.1038/s41467-024-49477-6 -
BMJ Paediatrics Open Jun 2024To determine the dose-dependent associations between antenatal corticosteroids (ANS) exposure and the rates of major morbidities, and the early weight loss percentage...
Association of different doses of antenatal corticosteroids exposure with early major outcomes and early weight loss percentage in extremely preterm infants or extremely low birthweight infants: a multicentre cohort study.
OBJECTIVES
To determine the dose-dependent associations between antenatal corticosteroids (ANS) exposure and the rates of major morbidities, and the early weight loss percentage (EWLP) in hospital among extremely preterm infants (EPI) or extremely low birthweight infants (ELBWI).
METHODS
A multicentre, retrospective cohort study of EPI or ELBWI born between 2017 and 2018 was conducted. Infants were classified into no ANS, partial ANS and complete ANS exposure group; three subgroups were generated by gestational age and birth weight. Multiple logistic regression and multiple linear regression were performed.
RESULTS
There were 725 infants included from 32 centres. Among no ANS, partial ANS and complete ANS exposure, there were significant differences in the proportions of bronchopulmonary dysplasia (BPD) (24.5%, 25.4% and 16.1%), necrotising enterocolitis (NEC) (6.7%, 2.0% and 2.0%) and death (29.6%, 18.5% and 13.5%), and insignificant differences in the proportions of intraventricular haemorrhage (IVH) (12.5%, 13.2% and 12.2%), and extrauterine growth restriction (EUGR) (50.0%, 56.6% and 59.5%). In the logistic regression, compared with no ANS exposure, complete ANS reduced the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91), NEC (OR 0.21, 95% CI 0.08 to 0.57) and death (OR 0.36, 95% CI 0.23 to 0.56), and partial ANS reduced the risk of NEC (OR 0.23, 95% CI 0.07 to 0.72) and death (OR 0.54, 95% CI 0.34 to 0.87). Compared with partial ANS exposure, complete ANS decreased the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91). There were insignificant associations between ANS exposure and IVH, EUGR. In the multiple linear regression, partial and complete ANS exposure increased EWLP only in the ≥28 weeks (w) and <1000 g subgroup (p<0.05).
CONCLUSIONS
Different doses of ANS (dexamethasone) exposure were protectively associated with BPD, NEC, death in hospital, but not EUGR at discharge among EPI or ELBWI. Beneficial dose-dependent associations between ANS (dexamethasone) exposure and BPD existed. ANS exposure increased EWLP only in the ≥28 w and<1000 g subgroup. ANS administration, especially complete ANS, is encouraged before preterm birth.
TRIAL REGISTRATION NUMBER
NCT06082414.
Topics: Humans; Infant, Newborn; Female; Infant, Extremely Low Birth Weight; Retrospective Studies; Infant, Extremely Premature; Male; Pregnancy; Weight Loss; Enterocolitis, Necrotizing; Bronchopulmonary Dysplasia; Dose-Response Relationship, Drug; Adrenal Cortex Hormones; Gestational Age; Infant, Premature, Diseases
PubMed: 38897621
DOI: 10.1136/bmjpo-2024-002506 -
Diagnostics (Basel, Switzerland) May 2024The early detection of esophageal cancer presents a substantial difficulty, which contributes to its status as a primary cause of cancer-related fatalities. This study...
The early detection of esophageal cancer presents a substantial difficulty, which contributes to its status as a primary cause of cancer-related fatalities. This study used You Only Look Once (YOLO) frameworks, specifically YOLOv5 and YOLOv8, to predict and detect early-stage EC by using a dataset sourced from the Division of Gastroenterology and Hepatology, Ditmanson Medical Foundation, Chia-Yi Christian Hospital. The dataset comprised 2741 white-light images (WLI) and 2741 hyperspectral narrowband images (HSI-NBI). They were divided into 60% training, 20% validation, and 20% test sets to facilitate robust detection. The images were produced using a conversion method called the spectrum-aided vision enhancer (SAVE). This algorithm can transform a WLI into an NBI without requiring a spectrometer or spectral head. The main goal was to identify dysplasia and squamous cell carcinoma (SCC). The model's performance was evaluated using five essential metrics: precision, recall, F1-score, mAP, and the confusion matrix. The experimental results demonstrated that the HSI model exhibited improved learning capabilities for SCC characteristics compared with the original RGB images. Within the YOLO framework, YOLOv5 outperformed YOLOv8, indicating that YOLOv5's design possessed superior feature-learning skills. The YOLOv5 model, when used in conjunction with HSI-NBI, demonstrated the best performance. It achieved a precision rate of 85.1% (CI95: 83.2-87.0%, < 0.01) in diagnosing SCC and an F1-score of 52.5% (CI95: 50.1-54.9%, < 0.01) in detecting dysplasia. The results of these figures were much better than those of YOLOv8. YOLOv8 achieved a precision rate of 81.7% (CI95: 79.6-83.8%, < 0.01) and an F1-score of 49.4% (CI95: 47.0-51.8%, < 0.05). The YOLOv5 model with HSI demonstrated greater performance than other models in multiple scenarios. This difference was statistically significant, suggesting that the YOLOv5 model with HSI significantly improved detection capabilities.
PubMed: 38893655
DOI: 10.3390/diagnostics14111129 -
Cancers Jun 2024This study addresses the critical need for the accurate diagnosis and management of intraductal papillary mucinous neoplasms (IPMNs), which are pancreatic cystic...
Navigating Intraductal Papillary Mucinous Neoplasm Management through Fukuoka Consensus vs. European Evidence-Based Guidelines on Pancreatic Cystic Neoplasms-A Study on Two European Centers.
This study addresses the critical need for the accurate diagnosis and management of intraductal papillary mucinous neoplasms (IPMNs), which are pancreatic cystic neoplasm types holding a substantial potential for malignancy. It evaluates the diagnostic effectiveness of the Fukuoka consensus guidelines and the European evidence-based guidelines in detecting high-grade dysplasia/invasive carcinoma in IPMNs, utilizing a retrospective analysis of 113 patients from two European medical centers. The methods include a comparative analysis of clinical, radiological, and endoscopic ultrasonography data, alongside an assessment of guideline-driven diagnostic performance. The results demonstrate that both guidelines offer similar accuracy in identifying severe disease stages in IPMNs, with certain clinical markers-such as jaundice, solid mass presence, and an increase in CA 19-9 levels-being pivotal in predicting the need for surgical intervention. This study concludes that while both guidelines provide valuable frameworks for IPMN management, there is an inherent need for further research to refine these protocols and improve patient-specific treatment strategies. This research contributes to the ongoing discourse on optimizing diagnostic and treatment paradigms for pancreatic cystic neoplasms, aiming to enhance clinical outcomes and patient care in this challenging medical field.
PubMed: 38893274
DOI: 10.3390/cancers16112156 -
Cancers May 2024Epigenetic biomarkers in cancer have emerged as promising tools for early detection, prognosis, and treatment response prediction. In cervical cells, hypermethylation of...
BACKGROUND
Epigenetic biomarkers in cancer have emerged as promising tools for early detection, prognosis, and treatment response prediction. In cervical cells, hypermethylation of the host and viral HPV-genome increases with the severity of lesions, providing a useful biomarker in the triage of hr-HPV-positive women and during treatment. The present study focuses on evaluating the clinical performance of the FAM19A4/miR124-2 methylation test in a population-based cervical screening program.
METHODS
Previously collected cervical samples, after bisulfite-converted DNA, were analyzed by PreCursor-M+ kit (distributed by Fujirebio Europe), for DNA methylation. The sensitivity, specificity, and negative/positive predictive values of DNA methylation were compared to histology, colposcopy, the HPV-DNA test, and cytology results.
RESULTS
Among the 61-sample set, the specificity of methylation vs. positive histology (≥CIN2) and colposcopy (≥G2) were 87% and 90%, whereas the sensitivity was 50% and 33.3%, respectively. The combination of methylation analysis with standard methods increases diagnostic accuracy.
CONCLUSIONS
Overall, we found a good specificity of DNA methylation in comparison to currently used techniques. Further larger studies could support the use of FAM19A4/miR124-2 as reliable biomarkers in the prevention of cervical cancer as triage in the screening protocol.
PubMed: 38893107
DOI: 10.3390/cancers16111986 -
Journal of Clinical Medicine May 2024The World Health Organization's (WHO) 2022 update on the classification of odontogenic and maxillofacial bone tumors has revolutionized diagnostic and treatment...
The World Health Organization's (WHO) 2022 update on the classification of odontogenic and maxillofacial bone tumors has revolutionized diagnostic and treatment paradigms by integrating novel molecular insights. Fibro-osseous lesions of the maxillo-facial bones constitute a heterogeneous group encompassing fibrous dysplasia, Psammomatoid Ossifying Fibroma (PSOF), Juvenile Trabecular Ossifying Fibroma (JTOF), and other variants. Despite histological similarities, their distinct clinical manifestations and prognostic implications mandate precise differentiation. The intricacies of diagnosing fibro-osseous lesions pose challenges for pathologists, maxillofacial surgeons, dentists and oral surgeons, underscoring the importance of a systematic approach to ensure optimal patient management. Herein, we present two cases, fibrous dysplasia and Cemento-Ossifying Fibroma, detailing their clinical encounters and management strategies. Both patients provided informed consent for publishing their data and images, adhering to ethical guidelines.
PubMed: 38892944
DOI: 10.3390/jcm13113233 -
Journal of Clinical Medicine May 2024Endoscopic submucosal dissection is used to treat early gastric neoplasms. Compared with other endoscopic procedures, it requires higher doses of opioids, leading to...
Associations between Clinicopathological Characteristics and Intraoperative Opioid Requirements during Endoscopic Submucosal Dissection with Monitored Anesthesia Care: A Retrospective Study.
Endoscopic submucosal dissection is used to treat early gastric neoplasms. Compared with other endoscopic procedures, it requires higher doses of opioids, leading to adverse events during monitored anesthesia care. We investigated the correlations between clinicopathological characteristics and intraprocedural opioid requirements in patients who underwent endoscopic submucosal dissection under monitored anesthesia care. The medical records of patients who underwent endoscopic submucosal dissection under monitored anesthesia care were retrospectively reviewed. The dependent variable was the total dose of fentanyl administered during the dissection, while independent variables were patient demographics, the American Society of Anesthesiologists physical status classification, preoperative vital sign data, and the pathological characteristics of the neoplasm. Correlations between variables were examined using multiple regression analysis. : The study included 743 patients. The median total fentanyl dose was 100 mcg. Younger age (coefficient -1.37; 95% confidence interval [CI] -1.78 to -0.95), male sex (16.12; 95% CI 6.99-25.24), baseline diastolic blood pressure (0.44; 95% CI 0.04-0.85), neoplasm length (1.63; 95% CI 0.90-2.36), and fibrosis (28.59; 95% CI 17.77-39.42) were positively correlated with the total fentanyl dose. Total fentanyl dose was higher in the differentiated (16.37; 95% CI 6.40-26.35) and undifferentiated cancers group (32.53; 95% CI 16.95-48.11) than in the dysplasia group; no significant differences were observed among the others. The mid-anterior wall (22.69; 95% CI 1.25-44.13), mid-posterior wall (29.65; 95% CI 14.39-44.91), mid-greater curvature (28.77; 95% CI 8.56-48.98), and upper groups (30.06; 95% CI 5.01-55.12) had higher total fentanyl doses than the lower group, whereas doses did not significantly differ for the mid-lesser curvature group. : We identified variables that influenced opioid requirements during monitored anesthesia care for endoscopic submucosal dissection. These may help predict the needed opioid doses and identify factors affecting intraprocedural opioid requirements.
PubMed: 38892830
DOI: 10.3390/jcm13113119 -
Journal of Clinical Medicine May 2024Respiratory problems are frequent in newborns, and are mainly studied with chest X-rays, whereas CT scans are usually needed for the evaluation of rare malformations... (Review)
Review
Respiratory problems are frequent in newborns, and are mainly studied with chest X-rays, whereas CT scans are usually needed for the evaluation of rare malformations and diseases. Lung ultrasound (LUS] has been proposed as an alternative method of diagnosing a variety of respiratory conditions. In recent years, there has been a rapid increase in LUS studies, thanks to the ability of LUS to rapidly exclude complications and significantly reduce radiation exposure in this fragile population. We aimed to summarize the current knowledge about LUS. A literature search was conducted on the Medline and Cochrane databases using appropriate terms. The inclusion criteria were: English language and human species. Exclusion criteria were: non-English language, animal species, case reports, case series, non-systematic reviews, and editorials. The search returned 360 results. No Cochrane reviews were found. Titles and abstracts were screened, and 37 were finally considered. Studies concerning the use of lung ultrasound for the following conditions were presented: neonatal respiratory distress syndrome, transient tachypnea of the newborn, pneumothorax, pulmonary hemorrhage, pneumonia, bronchopulmonary dysplasia, and prediction of extubation success. We discussed the utility of LUS for the diagnosis and treatment of neonatal diseases according to the most recent literature.
PubMed: 38892818
DOI: 10.3390/jcm13113107 -
International Journal of Molecular... Jun 2024Arrhythmogenic cardiomyopathy (ACM) is an inherited myocardial disease at risk of sudden death. Genetic testing impacts greatly in ACM diagnosis, but gene-disease...
Arrhythmogenic cardiomyopathy (ACM) is an inherited myocardial disease at risk of sudden death. Genetic testing impacts greatly in ACM diagnosis, but gene-disease associations have yet to be determined for the increasing number of genes included in clinical panels. Genetic variants evaluation was undertaken for the most relevant non-desmosomal disease genes. We retrospectively studied 320 unrelated Italian ACM patients, including 243 cases with predominant right-ventricular (ARVC) and 77 cases with predominant left-ventricular (ALVC) involvement, who did not carry pathogenic/likely pathogenic (P/LP) variants in desmosome-coding genes. The aim was to assess rare genetic variants in transmembrane protein 43 (), desmin (), phospholamban (), filamin c (), cadherin 2 (), and tight junction protein 1 (), based on current adjudication guidelines and reappraisal on reported literature data. Thirty-five rare genetic variants, including 23 (64%) P/LP, were identified in 39 patients (16/243 ARVC; 23/77 ALVC): 22 , 9 , 2 , and 2 . No P/LP variants were found in and genes. Gene-based burden analysis, including P/LP variants reported in literature, showed significant enrichment for (3.79-fold), (10.31-fold), (117.8-fold) and (107-fold). A non-desmosomal rare genetic variant is found in a minority of ARVC patients but in about one third of ALVC patients; as such, clinical decision-making should be driven by genes with robust evidence. More than two thirds of non-desmosomal P/LP variants occur in FLNC.
Topics: Humans; Arrhythmogenic Right Ventricular Dysplasia; Female; Male; Adult; Middle Aged; Membrane Proteins; Cadherins; Desmosomes; Genetic Predisposition to Disease; Genetic Variation; Filamins; Retrospective Studies; Italy; Calcium-Binding Proteins; Antigens, CD
PubMed: 38892455
DOI: 10.3390/ijms25116267