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Investigative Ophthalmology & Visual... Jun 2024We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene.
PURPOSE
We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene.
METHODS
Fifty-three patients (mean age, 33.6 ± 16.7 years) with Usher syndrome owing to biallelic, mostly pathogenic, variants in MYO7A underwent baseline and two annual follow-up visits. Best-corrected visual acuity (BCVA), semiautomatic kinetic visual field, full-field electroretinogram, color fundus imaging, microperimetry, spectral-domain optical coherence tomography, and fundus autofluorescence were assessed.
RESULTS
At baseline, all patients presented with decreased BCVA (66.4 ± 17.9 Early Treatment Diabetic Retinopathy score and 59.5 ± 21.7 Early Treatment Diabetic Retinopathy score, in the better- and worse-seeing eyes, respectively), restricted semiautomatic kinetic visual field (III4e area, 3365.8 ± 4142.1°2; 4176.4 ± 4400.3°2) and decreased macular sensitivity (9.7 ± 9.9 dB; 9.0 ± 10.2 dB). Spectral-domain optical coherence tomography revealed reduced central macular thickness (259.6 ± 63.0 µm; 250.7 ± 63.3 µm) and narrowed ellipsoid zone band width (2807.5 ± 2374.6 µm; 2615.5 ± 2370.4 µm). Longitudinal analyses (50 patients) showed a significant decrease of BCVA in better-seeing eyes, whereas no changes were observed in worse-seeing eyes for any parameter. BCVA, semiautomatic kinetic visual field (III4e and V4e) and macular sensitivity were related significantly to age at baseline. Hyperautofluorescent foveal patch (16 eyes [31.4%]) and abnormal central hypoautofluorescence (9 eyes [17.6%]) were significantly associated with worse morphological and functional read-outs compared with the hyperautofluorescent ring pattern (22 eyes [43.1%]).
CONCLUSIONS
Our European multicentric study offers the first prospective longitudinal analysis in one of the largest cohorts of MYO7A patients described to date, confirming the slow disease progression. More important, this study emphasizes the key role of fundus autofluorescence patterns in retinal impairment staging and advocates its adoption as an objective biomarker in patient selection for future gene therapy clinical trials.
Topics: Humans; Male; Female; Adult; Prospective Studies; Tomography, Optical Coherence; Visual Acuity; Middle Aged; Electroretinography; Myosin VIIa; Visual Fields; Young Adult; Adolescent; Usher Syndromes; Genetic Therapy; Child; Visual Field Tests; Europe; Fluorescein Angiography; Follow-Up Studies; Aged; Longitudinal Studies; Disease Progression; Myosins; Retina
PubMed: 38884554
DOI: 10.1167/iovs.65.6.25 -
Cureus May 2024Coronary artery aneurysms (CAAs) due to an immunoglobulin G4 (IgG4)-related disease (IgG4-RD) are relatively rare, and there is no consensus on the choice of treatment...
Coronary artery aneurysms (CAAs) due to an immunoglobulin G4 (IgG4)-related disease (IgG4-RD) are relatively rare, and there is no consensus on the choice of treatment method. In the present study, we report the results of the surgical treatment for multiple giant CAAs caused by IgG4-RD. A 71-year-old man was diagnosed with severe aortic regurgitation and CAAs. A blood test showed high IgG4 levels, and computed tomography revealed four giant coronary artery aneurysms: two in the right coronary artery (RCA) (proximal RCA and posterior descending artery (PDA)), one in the left anterior descending (LAD), and one in the diagonal branch (Dx). We planned aortic valve replacement, coronary aneurysm resection, and coronary artery bypass grafting (CABG). After finishing aortic valve replacement, the CAAs in proximal RCA, LAD, and Dx were resected. The proximal and distal tracts of the aneurysm were closed with a pericardial bovine patch and ligation. However, since the distal PDA was too calcified to be anastomosed, and the PDA aneurysm was smaller than the others, it was decided to leave the PDA aneurysm. The anastomoses of SVG-RCA and Dx, as well as the left internal thoracic artery to LAD, were performed. Histopathological examination of the aneurysm wall showed a high IgG4-positive cell/IgG-positive cell ratio, and a diagnosis of IgG4-RD was made. In the treatment of CAAs due to IgG4-RD, it is essential to select a procedure that takes into account the size, location, and nature of the aneurysm, and comorbidities. To ensure resection of the aneurysm and blockade of blood flow, closure of the inflow and outflow tracts with a pericardial bovine patch and CABG are effective.
PubMed: 38864041
DOI: 10.7759/cureus.60115 -
Frontiers in Oncology 2024The ability to dynamically adjust target contours, derived Boolean structures, and ultimately, the optimized fluence is the end goal of online adaptive radiotherapy...
INTRODUCTION
The ability to dynamically adjust target contours, derived Boolean structures, and ultimately, the optimized fluence is the end goal of online adaptive radiotherapy (ART). The purpose of this work is to describe the necessary tests to perform after a software patch installation and/or upgrade for an established online ART program.
METHODS
A patch upgrade on a low-field MR Linac system was evaluated for post-software upgrade quality assurance (QA) with current infrastructure of ART workflow on (1) the treatment planning system (TPS) during the initial planning stage and (2) the treatment delivery system (TDS), which is a TPS integrated into the delivery console for online ART planning. Online ART QA procedures recommended for post-software upgrade include: (1) user interface (UI) configuration; (2) TPS beam model consistency; (3) segmentation consistency; (4) dose calculation consistency; (5) optimizer robustness consistency; (6) CT density table consistency; and (7) end-to-end absolute ART dose and predicted dose measured including interruption testing. Differences of calculated doses were evaluated through DVH and/or 3D gamma comparisons. The measured dose was assessed using an MR-compatible A26 ionization chamber in a motion phantom. Segmentation differences were assessed through absolute volume and visual inspection.
RESULTS
(1) No UI configuration discrepancies were observed. (2) Dose differences on TPS pre-/post-software upgrade were within 1% for DVH metrics. (3) Differences in segmentation when observed were small in general, with the largest change noted for small-volume regions of interest (ROIs) due to partial volume impact. (4) Agreement between TPS and TDS calculated doses was 99.9% using a 2%/2-mm gamma criteria. (5) Comparison between TPS and online ART plans for a given patient plan showed agreement within 2% for targets and 0.6 cc for organs at risk. (6) Relative electron densities demonstrated comparable agreement between TPS and TDS. (7) ART absolute and predicted measured end-to-end doses were within 1% of calculated TDS.
DISCUSSION
An online ART QA program for post-software upgrade has been developed and implemented on an MR Linac system. Testing mechanics and their respective baselines may vary across institutions, but all necessary components for a post-software upgrade QA have been outlined and detailed. These outlined tests were demonstrated feasible for a low-field MR Linac system; however, the scope of this work may be applied and adapted more broadly to other online ART platforms.
PubMed: 38863634
DOI: 10.3389/fonc.2024.1358487 -
The Lancet. Digital Health Jul 2024Accurately distinguishing between malignant and benign thyroid nodules through fine-needle aspiration cytopathology is crucial for appropriate therapeutic intervention....
BACKGROUND
Accurately distinguishing between malignant and benign thyroid nodules through fine-needle aspiration cytopathology is crucial for appropriate therapeutic intervention. However, cytopathologic diagnosis is time consuming and hindered by the shortage of experienced cytopathologists. Reliable assistive tools could improve cytopathologic diagnosis efficiency and accuracy. We aimed to develop and test an artificial intelligence (AI)-assistive system for thyroid cytopathologic diagnosis according to the Thyroid Bethesda Reporting System.
METHODS
11 254 whole-slide images (WSIs) from 4037 patients were used to train deep learning models. Among the selected WSIs, cell level was manually annotated by cytopathologists according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) guidelines of the second edition (2017 version). A retrospective dataset of 5638 WSIs of 2914 patients from four medical centres was used for validation. 469 patients were recruited for the prospective study of the performance of AI models and their 537 thyroid nodule samples were used. Cohorts for training and validation were enrolled between Jan 1, 2016, and Aug 1, 2022, and the prospective dataset was recruited between Aug 1, 2022, and Jan 1, 2023. The performance of our AI models was estimated as the area under the receiver operating characteristic (AUROC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. The primary outcomes were the prediction sensitivity and specificity of the model to assist cyto-diagnosis of thyroid nodules.
FINDINGS
The AUROC of TBSRTC III+ (which distinguishes benign from TBSRTC classes III, IV, V, and VI) was 0·930 (95% CI 0·921-0·939) for Sun Yat-sen Memorial Hospital of Sun Yat-sen University (SYSMH) internal validation and 0·944 (0·929 - 0·959), 0·939 (0·924-0·955), 0·971 (0·938-1·000) for The First People's Hospital of Foshan (FPHF), Sichuan Cancer Hospital & Institute (SCHI), and The Third Affiliated Hospital of Guangzhou Medical University (TAHGMU) medical centres, respectively. The AUROC of TBSRTC V+ (which distinguishes benign from TBSRTC classes V and VI) was 0·990 (95% CI 0·986-0·995) for SYSMH internal validation and 0·988 (0·980-0·995), 0·965 (0·953-0·977), and 0·991 (0·972-1·000) for FPHF, SCHI, and TAHGMU medical centres, respectively. For the prospective study at SYSMH, the AUROC of TBSRTC III+ and TBSRTC V+ was 0·977 and 0·981, respectively. With the assistance of AI, the specificity of junior cytopathologists was boosted from 0·887 (95% CI 0·8440-0·922) to 0·993 (0·974-0·999) and the accuracy was improved from 0·877 (0·846-0·904) to 0·948 (0·926-0·965). 186 atypia of undetermined significance samples from 186 patients with BRAF mutation information were collected; 43 of them harbour the BRAF mutation. 91% (39/43) of BRAF-positive atypia of undetermined significance samples were identified as malignant by the AI models.
INTERPRETATION
In this study, we developed an AI-assisted model named the Thyroid Patch-Oriented WSI Ensemble Recognition (ThyroPower) system, which facilitates rapid and robust cyto-diagnosis of thyroid nodules, potentially enhancing the diagnostic capabilities of cytopathologists. Moreover, it serves as a potential solution to mitigate the scarcity of cytopathologists.
FUNDING
Guangdong Science and Technology Department.
TRANSLATION
For the Chinese translation of the abstract see Supplementary Materials section.
Topics: Humans; Thyroid Nodule; Deep Learning; China; Retrospective Studies; Biopsy, Fine-Needle; Prospective Studies; Female; Male; Middle Aged; Adult; Sensitivity and Specificity; Thyroid Gland; Aged; Thyroid Neoplasms
PubMed: 38849291
DOI: 10.1016/S2589-7500(24)00085-2 -
Acta Medica Philippina 2024To describe the treatment outcomes of patients who underwent coronary artery bypass grafting (CABG) with vein patch angioplasty with internal mammary artery (IMA)...
OBJECTIVE
To describe the treatment outcomes of patients who underwent coronary artery bypass grafting (CABG) with vein patch angioplasty with internal mammary artery (IMA) grafting of the diffusely diseased left anterior descending (LAD) coronary artery.
METHODS
This is a retrospective observational study of 26 patients who have undergone vein patch angioplasty of the LAD coronary artery with IMA grafting in three centers by a single surgeon from January 2012 to August 2017. The demographic profile, intraoperative data, and postoperative outcome (including in-hospital mortality and morbidity, perioperative myocardial infarction, and NYHA functional classification) were recorded. Continuous variables were expressed as means with standard deviation and categorical variables summarized as frequencies and percentages. Student's t-test was used to compare the preoperative versus postoperative mean NYHA functional class.
RESULTS
There were 22 (85%) males and 4 (15%) females with a mean age of 62 years (range: 34 to 82). Twenty-five patients (96%) had a three-vessel disease, and one (4%) had a two-vessel disease. Nine patients (35%) had a preoperative myocardial infarction. The mean cardiopulmonary bypass and aortic-cross clamp times were 156 and 118 minutes, respectively. The mean number of vessels grafted was 4.12. Multiple arterial grafting was used in seven patients (27%). There were two in-hospital mortalities (7.7%) and three morbidities (11.5%), including reoperation for bleeding, acute kidney injury, and leg wound infection. Six patients (23%) developed postoperative atrial fibrillation. No patient developed perioperative myocardial infarction. The mean ICU stay was three days, and the mean hospital stay was 10.27 days. The mean NYHA functional class improved from 2.85 preoperatively to 1.5 postoperatively (<0.00001). Among patients with improvement, postoperative NYHA improved by two functional classes in 38% and by one functional class in 62%.
CONCLUSION
Vein patch angioplasty is a valuable technique for diffuse coronary stenosis of the LAD artery with acceptable early results.
PubMed: 38846160
DOI: 10.47895/amp.vi0.7645 -
Indian Journal of Dermatology,... Apr 2024Background With the rise in cosmetic usage, adverse reactions related to cosmetics have also risen. Photocontact dermatitis to cosmetics is a challenging entity to...
Background With the rise in cosmetic usage, adverse reactions related to cosmetics have also risen. Photocontact dermatitis to cosmetics is a challenging entity to diagnose and manage. Objectives To evaluate the clinical features and photocontact sensitivity patterns in patients with cosmetic dermatitis and establish their association based on patch and photopatch test results. Methods A prospective observational study, where 80 patients with a clinical diagnosis of cosmetic dermatitis were patch or photopatch tested (as per indication) with the Indian standard series, Indian cosmetic and fragrance series, and the patient's personal product(s). Results A total of 104 positive reactions were observed in 57/80 patients, of which 50 were relevant to cosmetics usage. Sixty-five patients underwent a photopatch test, and 17 tested positive. Photosensitivity in patients was significantly associated with a positive photopatch test (p-value < 0.001). Various new photo-allergens were discovered, including propylene glycol, triethanolamine, chloroacetamide, isopropyl myristate, cetrimide and hexamine. Facial melanosis was a predominant clinical finding in 44 patients, with pigmented contact dermatitis detected in 19 (43.2%) of these cases. Limitations Patients' personal products could not be tested on every patient. Chemical analysis of indigenous products and the individual chemical ingredients of the patient's personal products could not be patch-tested separately. Phototesting was not performed in patients with photosensitivity. Conclusion In patients with suspected cosmetic dermatitis with history of photosensitivity or those with facial melanosis of unknown origin, a photopatch test is crucial to detect potentially hidden photo allergens. Many new photo allergens have emerged in the present study. Cosmetic companies should provide detailed information regarding each constituent of the cosmetic products.
PubMed: 38841970
DOI: 10.25259/IJDVL_1110_2022 -
Materials Today. Bio Jun 2024Developing patches that effectively merge intrinsic deformation characteristics of cardiac with superior tunable mechanical properties remains a crucial biomedical...
Developing patches that effectively merge intrinsic deformation characteristics of cardiac with superior tunable mechanical properties remains a crucial biomedical pursuit. Currently used traditional block-shaped or mesh patches, typically incorporating a positive Poisson's ratio, often fall short of matching the deformation characteristics of cardiac tissue satisfactorily, thus often diminishing their repairing capability. By introducing auxeticity into the cardiac patches, this study is trying to present a beneficial approach to address these shortcomings of the traditional patches. The patches, featuring the auxetic effect, offer unparalleled conformity to the cardiac complex mechanical challenges. Initially, scaffolds demonstrating the auxetic effect were designed by merging chiral rotation and concave angle units, followed by integrating scaffolds with a composite hydrogel through thermally triggering, ensuring excellent biocompatibility closely mirroring heart tissue. Tensile tests revealed that auxetic patches possessed superior elasticity and strain capacity exceeding cardiac tissue's physiological activity. Notably, Model III showed an equivalent modulus ratio and Poisson's ratio closely toward cardiac tissue, underscoring its outstanding mechanical potential as cardiac patches. Cyclic tensile loading tests demonstrated that Model III withstood continuous heartbeats, showcasing outstanding cyclic loading and recovery capabilities. Numerical simulations further elucidated the deformation and failure mechanisms of these patches, leading to an exploration of influence on mechanical properties with alternative design parameters, which enabled the customization of mechanical strength and Poisson's ratio. Therefore, this research presents substantial potential for designing cardiac auxetic patches that can emulate the deformation properties of cardiac tissue and possess adjustable mechanical parameters.
PubMed: 38840795
DOI: 10.1016/j.mtbio.2024.101098 -
Scientific Reports Jun 2024To date, degraded mangrove ecosystem restoration accomplished worldwide primarily aligns towards rehabilitation with monotypic plantations, while ecological restoration...
To date, degraded mangrove ecosystem restoration accomplished worldwide primarily aligns towards rehabilitation with monotypic plantations, while ecological restoration principles are rarely followed in these interventions. However, researchers admit that most of these initiatives' success rate is not appreciable often. An integrative framework of ecological restoration for degraded mangroves where site-specific observations could be scientifically rationalized, with co-located reference pristine mangroves as the target ecosystem to achieve is currently distinctively lacking. Through this experimental scale study, we studied the suitability of site-specific strategies to ecologically restore degraded mangrove patches vis-à-vis the conventional mono-species plantations in a highly vulnerable mangrove ecosystem in Indian Sundarbans. This comprehensive restoration framework was trialed in small discrete degraded mangrove patches spanning ~ 65 ha. Site-specific key restoration components applied are statistically validated through RDA analyses and Bayesian t-tests. 25 quantifiable metrics evaluate the restoration success of a ~ 3 ha degraded mangrove patch with Ridgeline distribution, Kolmogorov-Smirnov (K-S) tests, and Mahalanobis Distance (D) measure to prove the site's near-equivalence to pristine reference in multiple ecosystem attributes. This restoration intervention irrevocably establishes the greater potential of this framework in the recovery of ecosystem functions and self-sustenance compared to that of predominant monoculture practices for vulnerable mangroves.
Topics: Wetlands; India; Conservation of Natural Resources; Ecosystem; Environmental Restoration and Remediation; Pilot Projects; Bayes Theorem
PubMed: 38839775
DOI: 10.1038/s41598-024-63281-8 -
Channels (Austin, Tex.) Dec 2024Alterations in ion channel expression and function known as "electrical remodeling" contribute to the development of hypertrophy and to the emergence of arrhythmias and...
Alterations in ion channel expression and function known as "electrical remodeling" contribute to the development of hypertrophy and to the emergence of arrhythmias and sudden cardiac death. However, comparing current density values - an electrophysiological parameter commonly utilized to assess ion channel function - between normal and hypertrophied cells may be flawed when current amplitude does not scale with cell size. Even more, common routines to study equally sized cells or to discard measurements when large currents do not allow proper voltage-clamp control may introduce a selection bias and thereby confound direct comparison. To test a possible dependence of current density on cell size and shape, we employed whole-cell patch-clamp recording of voltage-gated sodium and calcium currents in Langendorff-isolated ventricular cardiomyocytes and Purkinje myocytes, as well as in cardiomyocytes derived from trans-aortic constriction operated mice. Here, we describe a distinct inverse relationship between voltage-gated sodium and calcium current densities and cell capacitance both in normal and hypertrophied cells. This inverse relationship was well fit by an exponential function and may be due to physiological adaptations that do not scale proportionally with cell size or may be explained by a selection bias. Our study emphasizes the need to consider cell size bias when comparing current densities in cardiomyocytes of different sizes, particularly in hypertrophic cells. Conventional comparisons based solely on mean current density may be inadequate for groups with unequal cell size or non-proportional current amplitude and cell size scaling.
Topics: Myocytes, Cardiac; Animals; Cell Size; Cardiomegaly; Mice; Male; Patch-Clamp Techniques
PubMed: 38836323
DOI: 10.1080/19336950.2024.2361416 -
Allergologie Select 2024Development, production, and marketing authorization of allergen products is generally challenging due to several specific characteristics, including the natural source... (Review)
Review
Development, production, and marketing authorization of allergen products is generally challenging due to several specific characteristics, including the natural source as well as the multitude of allergenic materials. Also, depending on the frequency of sensitization in the population, the number of patients available for inclusion in clinical trials can be a limiting factor for product development. In the development of allergen products for diagnosis of type I and type IV allergies these challenges are particularly demanding because, in contrast to certain products for allergen-specific immunotherapy, no exemptions from marketing authorization are foreseen for this product group in Directive 2001/83/EC. Thus, the regulatory framework is constantly adapted within the legal scope in order to balance necessary regulatory requirements ensuring quality, safety, and efficacy with the clinical need for a comprehensive range of diagnostic allergen products. In this article, we give an overview on the current regulatory framework for development and marketing authorization of allergen products for diagnosis of rare type I and type IV allergies.
PubMed: 38835748
DOI: 10.5414/ALX02505E