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The Journal of Pediatrics Jun 2024To demonstrate a high-yield molecular diagnostic workflow for lateralized overgrowth (LO), a congenital condition with abnormal enlargement of body parts, and to...
OBJECTIVE
To demonstrate a high-yield molecular diagnostic workflow for lateralized overgrowth (LO), a congenital condition with abnormal enlargement of body parts, and to classify it by molecular genetics. and STUDY DESIGN: We categorized 186 retrospective cases of LO diagnosed between 2003 and 2023 into suspected Beckwith-Wiedemann spectrum (BWSp), PIK3CA-Related Overgrowth Spectrum (PROS), vascular overgrowth (VO) , or isolated (ILO), based on initial clinical assessments, to determine the appropriate first-tier molecular tests and tissue for analysis. Patients underwent testing for 11p15 epigenetic abnormalities or somatic variants in genes related to PI3K/AKT/mTOR, vascular proliferation, and RAS-MAPK cascades using blood or skin DNA. For cases with negative initial tests, a sequential cascade molecular approach was employed to improve diagnostic yield.
RESULTS
This approach led to a molecular diagnosis in 54% of cases, 89% of cases consistent with initial clinical suspicions and 11% reclassified. BWSp was the most common cause, with 43% of cases exhibiting 11p15 abnormalities. PROS had the highest confirmation rate, with 74% of clinically diagnosed patients showing a PIK3CA variant. VO demonstrated significant clinical overlap with other syndromes. Molecular diagnosis of ILO proved challenging, with only 21% of cases classifiable into a specific condition.
CONCLUSION
Despite, LO is underdiagnosed from a molecular viewpoint and to date has had no diagnostic guidelines, which would be crucial for addressing potential cancer predisposition, enabling precision medicine treatments, or guiding management. This study sheds light on the molecular etiology of LO, highlighting the importance of tailored diagnostic approach and of selecting appropriate testing to achieve the highest diagnostic yield.
PubMed: 38945442
DOI: 10.1016/j.jpeds.2024.114177 -
Acta Biomaterialia Jun 2024This paper presents an inverse finite element (FE) approach aimed at estimating multi-layered human penile tissues. The inverse FE approach integrates experimental...
This paper presents an inverse finite element (FE) approach aimed at estimating multi-layered human penile tissues. The inverse FE approach integrates experimental force-displacement and boundary deformation data of penile tissues with a developed FE model and uses new experimental data on human penile tissue. The experimental study encompasses whole organ plate-compression tests and individual layer tensile and compression tests, providing comprehensive insights into the tissue's mechanical behaviour. The biomechanical characterisation of penile tissue is of crucial significance for understanding its mechanical behaviour under various physiological and pathological conditions. The FE model is constructed using the realistic geometry of the penile segment and appropriate constitutive models for each tissue layer to leverage the accuracy and consistency of the model. Through systematic variation of tissue parameters in the inverse FE algorithm, simulations achieve the best match with both force-displacement and deformed boundary results obtained from the whole organ plate-compression tests. Test results from individual tissue layers are also utilised to assess the estimated parameters. The proposed inverse FE approach allows for the estimation of penile tissue parameters with high precision and reliability, shedding light on the mechanical properties of this complex biological organ. This work has applications not only in urology but also for researchers in various disciplines of biomechanics. As a result, our study contributes to advancing the understanding of human penile tissue mechanics whilst the methodology could also be applied to a range of other soft biological tissues. STATEMENT OF SIGNIFICANCE: This research uses a multi-target inverse finite element (FE) approach for estimating the material parameters of human penile tissues. By integrating experimental data and a realistic FE model, this study achieves high-precision constitutive model parameter estimation, offering key insights into penile tissue mechanics under various loading conditions. The significance of this work lies in the use of this inverse FE approach for fresh-frozen human penile tissues, to identify the mechanical properties and constitutive models for both segregated tunica albuginea and corpus cavernosum as well as intact penile tissue segments. The study's scientific impact lies in its advancement of the understanding of human urological tissue mechanics, impacting researchers and clinicians alike.
PubMed: 38945188
DOI: 10.1016/j.actbio.2024.06.035 -
Journal of the Mechanical Behavior of... Jun 2024Micro finite-element (μFE) simulations serve as a crucial research tool to assist laboratory experiments in the biomechanical assessment of screw anchorage in bone....
Micro finite-element (μFE) simulations serve as a crucial research tool to assist laboratory experiments in the biomechanical assessment of screw anchorage in bone. However, accurately modelling the interface between bone and screw threads at the microscale poses a significant challenge. Currently, the gold-standard approach involves employing computationally intensive physical contact models to simulate this interface. This study compared nonlinear μFE predictions of deformations, whole-construct stiffness, maximum force and damage patterns of three different computationally efficient simplified interface approaches to the general contact interface in Abaqus Explicit, which was defined as gold-standard and reference model. The μCT images (resolution: 32.8 μm) of two human radii with varying bone volume fractions were utilized and a screw was virtually inserted up to 50% and 100% of the volar-dorsal cortex distance. Materially nonlinear μFE models were generated and loaded in tension, compression and shear. In a first step, the common simplification of using a fully-bonded interface was compared to the general contact interface, revealing overestimations of whole-construct stiffness (19% on average) and maximum force (26% on average), along with inaccurate damage pattern replications. To enhance predictions, two additional simplified interface models were compared: tensionally strained element deletion (TED) and a novel modification of TED (TED-M). TED deletes interface elements strained in tension based on a linear-elastic simulation before the actual simulation. TED-M extends the remaining contact interface of TED by incorporating neighboring elements to the contact area. Both TED and TED-M reduced the errors in whole-construct stiffness and maximum force and improved the replication of the damage distributions in comparison to the fully-bonded approach. TED was better in predicting whole-construct stiffness (average error of 1%), while TED-M showed lowest errors in maximum force (1% on average). In conclusion, both TED and TED-M offer computationally efficient alternatives to physical contact modelling, although the fully-bonded interface may deliver sufficiently accurate predictions for many applications.
PubMed: 38945119
DOI: 10.1016/j.jmbbm.2024.106634 -
International Journal of Surgery Case... Jun 2024Oblique facial clefts are uncommon congenital facial deformities. Among them, Tessier No. 3 cleft is an even rare malformation. This study presents a reconstructive...
INTRODUCTION AND IMPORTANCE
Oblique facial clefts are uncommon congenital facial deformities. Among them, Tessier No. 3 cleft is an even rare malformation. This study presents a reconstructive option and curative effect for oblique facial cleft deformity of Tessier No. 3.
CASE PRESENTATION
A 10-year-old girl was admitted to our hospital with "congenital facial deformity of right nose and mid-face". The clinical diagnosis was "oblique facial cleft of Tessier classification No. 3", also known as "naso-orbital cleft". The cleft was surgically repaired with an adjacent flap and nasolabial flap. After surgery, the case underwent uneventful healing with a surviving flap, and the deformity was well repaired. At 3 months to 1 year of follow-up, the flap had a similar feature (color and texture) to the contralateral tissue. A good outcome was obtained with minimal scar and face deformity.
CLINICAL DISCUSSION
Facial cleft is a clinical type of craniofacial cleft. The soft tissue feature of Tessier No. 3 cleft is that the fissure is located in the joint part of the middle nose, lateral nose, and maxillary process. The operation adopts the method of closing the fissure with soft tissue flap and pedicled flap transplantation is a priority method. In this clinical case, the patient with oblique facial cleft of Tessier classification No. 3 was repaired by the adjacent flap and nasolabial flap.
CONCLUSION
The application of the adjacent flap and nasolabial flap is a viable option for the reconstruction of oblique facial cleft deformity of Tessier No. 3 in oral surgery.
PubMed: 38945016
DOI: 10.1016/j.ijscr.2024.109981 -
BMC Pulmonary Medicine Jun 2024For patients with congenital heart disease-related pulmonary arterial hypertension (CHD-PAH), cardiopulmonary exercise testing (CPET) can reflect cardiopulmonary reserve...
BACKGROUND
For patients with congenital heart disease-related pulmonary arterial hypertension (CHD-PAH), cardiopulmonary exercise testing (CPET) can reflect cardiopulmonary reserve function. However, CPET may not be readily accessible for patients with high-risk conditions or limited mobility due to disability. Echocardiography, on the other hand, serves as a widely available diagnostic tool for all CHD-PAH patients. This study was aimed to identify the parameters of echocardiography that could serve as indicators of cardiopulmonary function and exercise capacity.
METHODS
A cohort of 70 patients contributed a total of 110 paired echocardiogram and CPET results to this study, with 1 year interval for repeated examinations. Echocardiography and exercise testing were conducted following standardized procedures, and the data were collected together with clinically relevant indicators for subsequent statistical analysis. Demographic comparisons were performed using t-tests and chi-square tests. Univariate and multivariate analyses were conducted to identify potential predictors of peak oxygen uptake (peak VO) and the carbon dioxide ventilation equivalent slope (VE/VCO slope). Receiver operating characteristic (ROC) analysis was used to assess the performance of the parameters.
RESULTS
The ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) was found to be the only independent indicator significantly associated with both peak VO and VE/VCO slope (both p < 0.05). Additionally, left ventricular ejection fraction (LVEF) and right ventricular fractional area change (FAC) were independently correlated with the VE/VCO slope (both p < 0.05). TAPSE/PASP showed the highest area under the ROC curve (AUC) for predicting both a peak VO ≤ 15 mL/kg/min and a VE/VCO slope ≥ 36 (AUC = 0.91, AUC = 0.90, respectively). The sensitivity and specificity of TAPSE/PASP at the optimal threshold exceeded 0.85 for both parameters.
CONCLUSIONS
TAPSE/PASP may be a feasible echocardiographic indicator for evaluating exercise tolerance.
Topics: Humans; Female; Male; Exercise Test; Heart Defects, Congenital; Echocardiography; Adult; ROC Curve; Exercise Tolerance; Pulmonary Arterial Hypertension; Oxygen Consumption; Middle Aged; Young Adult; Hypertension, Pulmonary; Pulmonary Artery
PubMed: 38944669
DOI: 10.1186/s12890-024-03113-7 -
Photodiagnosis and Photodynamic Therapy Jun 2024Diabetes, characterized by heightened blood sugar levels, can lead to a condition called Diabetic Retinopathy (DR), which adversely impacts the eyes due to elevated...
Diabetes, characterized by heightened blood sugar levels, can lead to a condition called Diabetic Retinopathy (DR), which adversely impacts the eyes due to elevated blood sugar affecting the retinal blood vessels. The most common cause of blindness in diabetics is thought to be Diabetic Retinopathy (DR), particularly in working-age individuals living in poor nations. People with type 1 or type 2 diabetes may develop this illness, and the risk rises with the length of diabetes and inadequate blood sugar management. There are limits to traditional approaches for the early identification of diabetic retinopathy (DR). In order to diagnose diabetic retinopathy, a model based on Convolutional neural network (CNN) is used in a unique way in this research. The suggested model uses a number of deep learning (DL) models, such as VGG19, Resnet50, and InceptionV3, to extract features. After concatenation, these characteristics are sent through the CNN algorithm for classification. By combining the advantages of several models, ensemble approaches can be effective tools for detecting diabetic retinopathy and increase overall performance and resilience. Classification and image recognition are just a few of the tasks that may be accomplished with ensemble approaches like combination of VGG19,Inception V3 and Resnet 50 to achieve high accuracy. The proposed model is evaluated using a publicly accessible collection of fundus images.VGG19, ResNet50, and InceptionV3 differ in their neural network architectures, feature extraction capabilities, object detection methods, and approaches to retinal delineation. VGG19 may excel in capturing fine details, ResNet50 in recognizing complex patterns, and InceptionV3 in efficiently capturing multi-scale features. Their combined use in an ensemble approach can provide a comprehensive analysis of retinal images, aiding in the delineation of retinal regions and identification of abnormalities associated with diabetic retinopathy. For instance, micro aneurysms, the earliest signs of DR, often require precise detection of subtle vascular abnormalities. VGG19's proficiency in capturing fine details allows for the identification of these minute changes in retinal morphology. On the other hand, ResNet50's strength lies in recognizing intricate patterns, making it effective in detecting neo neo-vascularization and complex hemorrhagic lesions. Meanwhile, InceptionV3's multi-scale feature extraction enables comprehensive analysis, crucial for assessing macular edema and ischemic changes across different retinal layers.
PubMed: 38944405
DOI: 10.1016/j.pdpdt.2024.104259 -
Journal of Stroke and Cerebrovascular... Jun 2024Anomalous vascular variants pose unique challenges in clinical management, especially in the context of neuroendovascular intervention. We present a case report...
Anomalous vascular variants pose unique challenges in clinical management, especially in the context of neuroendovascular intervention. We present a case report detailing an extremely rare anatomic variant involving the left anterior choroidal artery, which arises proximal to the fetal posterior communicating artery. Our patient presented with confusion and speech abnormalities following a benzodiazepine overdose. Subsequent computed tomography of the head revealed an aneurysm originating from the left supraclinoid carotid artery. This aneurysm was located 2 mm more proximal to the origin of the left posterior communicating artery and was initially misidentified as originating from the left posterior communicating artery due to its proximity. Further diagnostic cerebral angiography revealed an extremely rare anatomical variant where the left anterior choroidal artery anomalously arose proximal to a fetal posterior communicating artery, with the aneurysm being correctly identified as arising from the left anterior choroidal artery. The patient underwent successful detoxification and has since shown remarkable improvement, with plans for elective endovascular flow diversion treatment under dual antiplatelet therapy. Considering the critical role of the anterior choroidal artery in supplying vital cerebral structures, awareness of such variants is paramount to prevent inadvertent vascular injury and optimize patient outcomes. This case highlights the necessity of meticulous pre-procedural imaging and multidisciplinary collaboration in managing neurovascular anomalies effectively.
PubMed: 38944362
DOI: 10.1016/j.jstrokecerebrovasdis.2024.107835 -
The Journal of Foot and Ankle Surgery :... Jun 2024Ankle arthrodesis is an effective surgical intervention for end-stage arthritis or severe ankle joint deformity. Both internal (IF) and external fixation (EF) techniques... (Review)
Review
Ankle arthrodesis is an effective surgical intervention for end-stage arthritis or severe ankle joint deformity. Both internal (IF) and external fixation (EF) techniques are valid options, but there is controversy regarding the most effective technique. This study compares the safety and efficacy of EF and IF fixation techniques for ankle arthrodesis. A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Guidelines. A literature search of electronic databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL), was performed to identify all studies directly comparing the two techniques. Both fixed and random effects models of analysis were used depending on heterogeneity. Odds of union in the EF and IF groups were comparable (OR=0.60, CI 0.36-1.02, p=0.06) however, EF was associated with greater odds of deep hardware infections (OR=3.67, 1.97-6.83, p <0.05) and amputations (OR=3.17, CI 1.06-9.54, p =0.04). Odds of revision surgery and superficial wound complications were similar between groups. EF techniques had significantly longer operation times (MD=31.23, CI-25.11-37.34, p <0.05) and intraoperative blood loss (MD=46.31, CI-24.93-67.69, p <0.05). No significant difference was noted in pain and functionality scores. IF and EF techniques have reasonable union rates with similar postoperative outcomes. However, IF patients are more likely to achieve primary union and less likely to have deep infections, being mindful that EF techniques were usually indicated for more complex cases. LEVEL OF EVIDENCE: IV.
PubMed: 38944233
DOI: 10.1053/j.jfas.2024.05.010 -
Cell Reports. Medicine Jun 2024Solid tumor pathology, characterized by abnormalities in the tumor microenvironment (TME), challenges therapeutic effectiveness. Mechanical factors, including increased... (Review)
Review
Solid tumor pathology, characterized by abnormalities in the tumor microenvironment (TME), challenges therapeutic effectiveness. Mechanical factors, including increased tumor stiffness and accumulation of intratumoral forces, can determine the success of cancer treatments, defining the tumor's "mechanopathology" profile. These abnormalities cause extensive vascular compression, leading to hypoperfusion and hypoxia. Hypoperfusion hinders drug delivery, while hypoxia creates an unfavorable TME, promoting tumor progression through immunosuppression, heightened metastatic potential, drug resistance, and chaotic angiogenesis. Strategies targeting TME mechanopathology, such as vascular and stroma normalization, hold promise in enhancing cancer therapies with some already advancing to the clinic. Normalization can be achieved using anti-angiogenic agents, mechanotherapeutics, immune checkpoint inhibitors, engineered bacterial therapeutics, metronomic nanomedicine, and ultrasound sonopermeation. Here, we review the methods developed to rectify tumor mechanopathology, which have even led to cures in preclinical models, and discuss their bench-to-bedside translation, including the derivation of biomarkers from tumor mechanopathology for personalized therapy.
PubMed: 38944037
DOI: 10.1016/j.xcrm.2024.101626 -
International Journal of Surgery Case... Jun 2024Hepatic round ligament necrosis is a rare condition that has atypical clinical presentation. Its diagnosis; however, being a combination of clinical and biological...
INTRODUCTION AND IMPORTANCE
Hepatic round ligament necrosis is a rare condition that has atypical clinical presentation. Its diagnosis; however, being a combination of clinical and biological signs, is very dependent on the computed topography scan.
CASE PRESENTATION
This report demonstrates 2 cases that had different presentations. Case 1 was an elderly female with multiple comorbidities presenting with signs of sepsis, perturbation of liver enzymes and presence of thrombosis of portal vein as well as dilatation of bile ducts. On the other hand, case 2 was a younger male patient presenting with inflammatory syndrome, no other biological abnormalities and only an evident fatty stranding in his radiological workup.
CLINICAL DISCUSSION
Our 2 cases had different presentations in severity and were thus treated differently. The first patient had clinical, biological and radiological signs of severity; thus, he was treated surgically. On the other hand, the other patient with benign presentation was treated medically with antibiotics.
CONCLUSION
In the absence of recommendations concerning the management of hepatic round ligament necrosis, we suggest that treatment choice be based on the severity signs being: clinical, biological or radiological.
PubMed: 38943939
DOI: 10.1016/j.ijscr.2024.109966