Persistent Defects Research Articles

Skeletal progenitor LRP1 deficiency causes severe and persistent skeletal defects with Wnt pathway dysregulation

Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor whose dysfunction is linked to developmental dysplasia of the hip, osteoporosis and osteoarthritis. Our work addresses the critical question of how these skeletal pathologies emerge. Here, we show the abundant expression of LRP1 in skeletal progenitor cells at mouse embryonic stage E10.5 and onwards, especially in the perichondrium, the stem cell layer surrounding developing limbs essential for bone formation. Lrp1 deficiency in these stem cells causes joint fusion, malformation of cartilage/bone template and markedly delayed or lack of primary ossification. These abnormalities, which resemble phenotypes associated with Wnt signalling pathways, result in severe and persistent skeletal defects including a severe deficit in hip joint and patella, and markedly deformed and low-density long bones leading to dwarfism and impaired mobility. Mechanistically, we show that LRP1 regulates core non-canonical Wnt/planar cell polarity (PCP) components that may explain the malformation of long bones. LRP1 directly binds to Wnt5a, facilitates its cell-association and endocytic degradation and recycling. In the developing limbs, LRP1 partially colocalises with Wnt5a and its deficiency alters abundance and distribution of Wnt5a and Vangl2. Finally, using Xenopus as a model system, we show the regulatory role for LRP1 in Wnt/PCP signalling. We propose that in skeletal progenitors, LRP1 plays a critical role in formation and maturity of multiple bones and joints by regulating Wnt signalling, providing novel insights into the fundamental processes of morphogenesis and the emergence of skeletal pathologies.

The use of human albumin eye drops as an adjunctive therapy in cases of persistant corneal epithelial defects

Background Albumin eye drops (AED) can be effective in the healing of corneal epithelial defects. Albumin is the main protein component of autologous serum and therefore may be useful in the treatment of ocular surface diseases such as corneal ulcers and epithelial defects. Aim This work aimed to study the effect of human AED as adjunctive therapy in the treatment of persistent corneal epithelial defects (PCEDs). Patients and methods This prospective study was conducted in 20 patients aged 18–60 years, of both sexes, with PCEDs that did not respond to standard medical treatment for 10 to 14 days. All patients underwent slit-lamp examination, fundus examination, intraocular pressure measurement (digital), corneal swab, culture, and sensitivity. Results There was a significant positive correlation between the duration of medical therapy with the persistent antiepithelial defect AED and the size of the persistent epithelial defect at presentation (P<0.05). There was significant improvement in pain sensation, ciliary injection, persistent epithelial defect size, corneal, and stromal infiltration during the study period. There was no significant association between the duration of continuous ant epithelial drug therapy AED and stromal infiltration at presentation (P=0.627). Conclusion The promising therapeutic effects of AED on the corneal epithelium have been demonstrated. Albumin has shown a therapeutic effect in the treatment of PCEDs.

A difficult case of relapsing polychondritis that led to persistent obstructive ventilatory defect caused by tracheobronchomalacia

A difficult case of relapsing polychondritis that led to persistent obstructive ventilatory defect caused by tracheobronchomalacia

Combination of Biochar and Advanced Oxidation Processes for the Sustainable Elimination of Pharmaceuticals in Water

The presence of pharmaceuticals in aquatic ecosystems is an issue of increasing concern. Regardless of the low concentration of pharmaceuticals in water, they can have a toxic effect on both humans and aquatic organisms. Advanced oxidation processes (AOPs) have been described as a promising technique for eliminating pharmaceuticals due to their high efficiency. However, the cost associated with the application of these processes and their high reagents and energy requirements have affected the implementation of AOPs at large scales. Biochar has been suggested to be used as a catalyst in AOPs to overcome these limitations. Biochar is considered as an alternative heterogeneous catalyst thanks to its physicochemical characteristics like its specific surface area, porous structure, oxygen-containing functional groups, electrical conductivity, persistent free radicals (PFRs), modifiable properties, and structure defects. This carbonaceous material presents the capacity to activate oxidizing agents leading to the formation of radical species, which are needed to degrade pharmaceuticals. Additionally, AOP/biochar systems can destroy pharmaceutical molecules following a non-radical pathway. To enhance biochar catalytic performance, modifications have been suggested such as iron (Fe) impregnation, heteroatom doping, and supporting semiconductors on the biochar surface. Although biochar has been efficiently used in combination with several AOPs for the mineralization of pharmaceuticals from water, further research must be conducted to evaluate different regeneration techniques to increase biochar’s sustainable applicability and reduce the operational cost of the combined process. Moreover, operational conditions influencing the combined system are required to be evaluated to discern their effect and find conditions that maximize the degradation of pharmaceuticals by AOP/biochar systems.

A Novel Grid Strategy for Correlating Focal Macular Anatomic Changes With Focal Changes in Choriocapillaris Perfusion.

To establish the repeatability of choriocapillaris flow deficit (CCFD) measurements within a macular grid and then demonstrate the use of this registered grid strategy to follow CCFD measurements over time. Swept-source optical coherence tomography angiography scans were acquired (nominal size of 6 × 6mm). For each scan, masks of hyperreflective foci, calcified drusen, and persistent choroidal hypertransmission defects (hyperTDs) were generated. These masks were then used to exclude these prespecified regions when calculating the CCFD percentages (CCFD%). Scans were registered, and CCFD% measurements were performed within 3-mm and 5-mm fovea-centered circles and within a fovea-centered grid (one box: 74 × 74 pixels). The 95% minimal detectable changes (MDC95) for CCFD% were calculated for each of the regions. This longitudinal grid workflow was then used to study eyes before and after drusen resolved. Ninety eyes of 63 patients were identified: 30 normal eyes, 30 eyes with intermediate age-related macular degeneration (iAMD), and 30 eyes with hyperTDs. The MDC95 for the normal, iAMD, and hyperTD eyes within the 3-mm and 5-mm circles ranged from 0.85% to 1.96%. The MDC95 for an individual grid's box ranged from 3.35% to 4.67%, and for the total grid area, the MDC95 ranged from 0.91% to 1.40%. When tested longitudinally before and after the resolution of drusen using grid strategy, no significant differences in the CCFD% were observed. A grid strategy was developed to investigate targeted longitudinal changes in CCFD% associated with changes in optical coherence tomography biomarkers, and this strategy was validated using eyes in which drusen resolved.

Impact of submicron Nb3Sn stoichiometric surface defects on high-field superconducting radiofrequency cavity performance

Nb3Sn film coatings have the potential to drastically improve the accelerating performance of Nb superconducting radiofrequency (SRF) cavities in next-generation linear particle accelerators. Unfortunately, persistent Nb3Sn stoichiometric material defects formed during fabrication limit the cryogenic operating temperature and accelerating gradient by nucleating magnetic vortices that lead to premature cavity quenching. The SRF community currently lacks a predictive model that can explain the impact of chemical and morphological properties of Nb3Sn defects on vortex nucleation and maximum accelerating gradients. Both experimental and theoretical studies of the material and superconducting properties of the first 100 nm of Nb3Sn surfaces are complicated by significant variations in the volume distribution and topography of stoichiometric defects. This work contains a coordinated experimental study with supporting simulations to identify how the observed chemical composition and morphology of certain Sn-rich and Sn-deficient surface defects can impact the SRF performance. Nb3Sn films were prepared with varying degrees of stoichiometric defects, and the film surface morphologies were characterized. Both Sn-rich and Sn-deficient regions were identified in these samples. For Sn-rich defects, we focus on elemental Sn islands that are partially embedded into the Nb3Sn film. Using finite element simulations of the time-dependent Ginzburg-Landau equations, we estimate vortex nucleation field thresholds at Sn islands of varying size, geometry, and embedment. We find that these islands can lead to significant SRF performance degradation that could not have been predicted from the ensemble stoichiometry alone. For Sn-deficient Nb3Sn surfaces, we experimentally identify a periodic nanoscale surface corrugation that likely forms because of extensive Sn loss from the surface. Simulation results show that the surface corrugations contribute to the already substantial drop in the vortex nucleation field of Sn-deficient Nb3Sn surfaces. This work provides a systematic approach for future studies to further detail the relationship between experimental Nb3Sn growth conditions, stoichiometric defects, geometry, and vortex nucleation. These findings have technical implications that will help guide improvements to Nb3Sn fabrication procedures. Our outlined experiment-informed theoretical methods can assist future studies in making additional key insights about Nb3Sn stoichiometric defects that will help build the next generation of SRF cavities and support related superconducting materials development efforts. Published by the American Physical Society 2024

Comprehensive Proteomic Characterization of the Intra-Golgi Trafficking Intermediates.

Intracellular trafficking relies on small vesicular intermediates, though their specific role in Golgi function is still debated. To clarify this, we induced acute dysfunction of the Conserved Oligomeric Golgi (COG) complex and analyzed vesicles from cis, medial, and trans-Golgi compartments. Proteomic analysis of Golgi-derived vesicles from wild-type cells revealed distinct molecular profiles, indicating a robust recycling system for Golgi proteins. Notably, these vesicles retained various vesicular coats, while COG depletion accelerated uncoating. The increased overlap in molecular profiles with COG depletion suggests that persistent defects in vesicle tethering disrupt intra-Golgi sorting. Our findings reveal that the entire Golgi glycosylation machinery recycles within vesicles in a COG-dependent manner, whereas secretory and ER-Golgi trafficking proteins were not enriched. These results support a model in which the COG complex orchestrates multi-step recycling of glycosylation machinery, coordinated by specific Golgi coats, tethers, Rabs, and SNAREs.

Dexmedetomidine Alleviates the Long-Term Neurodevelopmental Toxicity Induced by Sevoflurane in the Developing Brain

Introduction: Sevoflurane is an extensively used anesthetic for pediatric patients; however, numerous studies showed that sevoflurane (SEVO) may cause long-term neurodevelopmental toxicity. Dexmedetomidine (DEX) has been shown to be protective against SEVO-induced neurotoxicity, but the mechanism remains unclear. The effects and mechanisms of different DEX administration routes on SEVO-induced neurotoxicity and long-term cognitive defects were determined and further investigated the role of sex in these processes. Methods: Male and female Sprague Dawley rats at postnatal day 7 (PND7) received an intraperitoneal injection of DEX (10 μg/kg) before or after exposure to 2.5% SEVO for 6 h, or before and after SEVO exposure. The respiratory and mortality rates of the pups were recorded during anesthesia. Neuroapoptosis was evaluated by TdT-mediated dUTP nick-end labeling staining. Immunohistochemistry and immunofluorescence were employed to detect the expression of caspase-3 in neuronal cells and neurons. The expression of GSK-3β and DISC1 was determined by Western blotting or RT-qPCR. Morris water maze (MWM) test was used to evaluate the learning and memory ability of rats until they were 3 weeks and 5 weeks old. Results: Compared with the control group, exposure to 2.5% SEVO resulted in increased neuroapoptosis and decreased the expression of DISC1 at levels of mRNA and protein and phosphorylated GSK-3β in the developing brain. SEVO exposure during critical neurodevelopmental periods could cause persistent cognitive defects in adolescent male and female rats and inhibited DISC1 and phosphorylated GSK-3β protein expression. The neurotoxic impacts of SEVO were lessened by the administration of DEX (10 μg/kg) before or after exposure. Conclusion: Our findings suggest that DEX (10 μg/kg) mitigates the neurotoxic effects of SEVO on the developing rat brain as well as postnatal cognitive defects by regulating the DISC1/GSK-3β signaling.

Comparison Between Optical Coherence Tomography B-scan and En Face Imaging for the Diagnosis of Early Macular Atrophy in Age-Related Macular Degeneration

The gradings of complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) and incomplete RPE and outer retinal atrophy (iRORA) on spectral domain optical coherence tomography (SD-OCT) B-scans were compared with the grading of persistent choroidal hypertransmission defects (hyperTDs) on swept-source optical coherence tomography angiography (SS-OCTA) en face images. Comparative diagnostic analysis of prospective study data. Patients with late nonexudative age-related macular degeneration underwent same-day 6×6-mm macular scans using both SD-OCT (Spectralis Heidelberg, 512×97, automatic real-time tracking: 9) and SS-OCTA (PLEX Elite 9000, Carl Zeiss Meditec, 500×500 angio pattern) instruments. SS-OCTA and SD-OCT en face images were generated from a sub-RPE slab positioned 64 to 400 µm below Bruch's membrane. SD-OCT B-scan gradings, which included an inspection of neighboring B-scans for the diagnosis of cRORA and iRORA, were performed at the Moran Eye Center, and gradings of en face images to identify persistent choroidal hyperTDs were performed at the Bascom Palmer Eye Institute and Tel Aviv Medical Center. There was a high degree of agreement (99.6%) between the gradings of cRORA lesions and persistent hyperTDs. However, 27.4% of iRORA lesions were found to be contained within persistent hyperTDs. This discrepancy was due to the finding that 27.5% of iRORA lesions were diagnosed as having a greatest linear horizontal dimension of <250 µm on B-scans, but on en face images, these B-scan-defined iRORA lesions were found to have the greatest linear dimensions in the nonhorizontal dimension that were ≥250 µm. This report demonstrates the benefits of using en face OCT imaging to identify cRORA lesions and highlights the need to acquire dense raster B-scans with the grading neighboring B-scans when identifying iRORA lesions to assess the full extent of the iRORA lesions in the nonhorizontal dimension. Although neighboring B-scans were inspected, 27.5% of iRORA lesions were actually part of larger cRORA lesions when graded using an en face strategy.

Usage of a new method of treatment of persistent corneal defects of various genesis

Usage of a new method of treatment of persistent corneal defects of various genesis

Exercise pulmonary hypertension in chronic thromboembolic pulmonary disease: A right heart catheterization study.

Many patients with chronic thromboembolic pulmonary disease (CTEPD) suffer from exertional dyspnea. It is unclear if CTEPD is associated with exercise pulmonary hypertension (ePH). This cross-sectional study aimed to determine the occurrence of ePH in patients with CTEPD and to identify the haemodynamic changes during exercise. We recruited 36 patients with persistent dyspnoea and residual perfusion defects by ventilation/perfusion scintigraphy from a large cohort of patients with previous pulmonary embolism. All patients underwent exercise right heart catheterization before being classified into the following groups: (1) CTEPD without ePH; comprising patients with normal mean pulmonary artery pressure (mPAP) of ≤20 mmHg, but with mPAP/cardiac output (CO) slope of ≤3 mmHg/L/min, (2) CTEPD with ePH (CTEPD-ePH); those with CTEPD with an mPAP/CO slope of >3 mmHg/L/min, (3) chronic thromboembolic pulmonary hypertension (CTEPH); those with mPAP >20 mmHg, pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg and pulmonary vascular resistance >2 WU. The postcapillary contribution during exercise was considered present if the PAWP/CO slope of >2 mmHg/L/min. CTEPD without resting pulmonary hypertension (PH) was present in 29 (81%) of the 36 patients, of whom six (21%) had ePH, while five (14%) had CTEPH. Two patients had unclassified PH. Two (33%) of the six patients with CTEPD-ePH had a PAWP/CO slope of >2 mmHg/L/min, compared with two (40%) of the five of those with CTEPH. In conclusion, about 20% of patients with CTEPD and exertional dyspnoea had ePH. Exercise right heart catheterization revealed a notable proportion of patients with postcapillary contribution.

Paragangliomas and syringomyelia in Tetralogy of Fallot-A case report and literature review.

Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries, paragangliomas, and syringomyelia are uncommon diseases. Furthermore, in the absence of any genetic link and with less than five reported adult patients surviving unrepaired rare form of Tetralogy of Fallot, our case shows noteworthiness. The possibility of definitive treatment of these conditions is rendered unsafe due to this persistent defect. Thus, management and ongoing survival of this patient remains complex and challenging.

CT-Guided Epidural Contrast Injection for the Identification of Dural Defects.

Post-dural puncture headache is an increasingly recognized cause of chronic headache. Outside of clinical history and myelography that requires an additional dural puncture, there is no reliable diagnostic test to evaluate for persistent dural defects. We describe the injection of iodinated contrast into the dorsal epidural space under CT guidance in 5 patients as a potential tool to visualize persistent dural defects.

Persistent defect in SARS-CoV-2 humoral and cellular immunity in lung transplant recipients

Lung transplant recipients (LTRs) are susceptible to severe Coronavirus Disease 2019 (COVID-19) and had lower immune responses to primary severe acute respiratory syndrome-related to coronavirus 2 (SARS-CoV-2) vaccination as compared to the general population and to other solid organ transplant recipients. As immunity induced by booster vaccination and natural infection has increased since the beginning of the pandemic in the general population, immunity acquired by LTRs is not well documented. Humoral and cellular immunity to SARS-CoV-2 was monitored in February and May 2023 in 30 LTRs and compared to that of health care workers (HCWs) and nursing home residents (NHRs). LTRs had significantly lower levels of SARS-CoV-2 binding and neutralizing antibodies and lower interferon-gamma responses to Wuhan, Delta, and XBB1.5 variants as compared to HCWs and NHRs. Humoral immunity decreased between the 2 visits,whereas cellular immunity remained more stable. The persistent defect in SARS-CoV-2 immunity in LTRs should encourage continued monitoring and preventive measures for this vulnerable population.

Reversible cerebral vasoconstriction syndrome post-cardiac transplantation: a therapeutic dilemma: case report

BackgroundReversible cerebral vasoconstriction syndrome (RCVS) is characterized by diffuse, multifocal segmental narrowing of cerebral arteries and can result in ischaemic stroke. Causal factors, identified in 60% of cases, include immunosuppressant pharmacotherapy. The few reports following heart transplantation are almost all in Asian recipients. We report on a Caucasian Australian patient with immunotherapy induced RCVS post heart transplantation to highlight the state of knowledge of the condition and the treatment dilemma it poses.Case presentationA 51-year-old female underwent orthotopic heart transplantation at our institution. Induction immunotherapy comprised basiliximab, mycophenolate mofetil and methylprednisolone. On day 6 post-transplantation the patient was transitioned to oral prednisolone and tacrolimus. On day 7 the patient began to experience bilateral, severe, transient occipital and temporal headaches. On day 9 tacrolimus dose was up-titrated. A non-contrast computed tomography brain (CTB) was normal. Endomyocardial biopsy on day 12 demonstrated moderate Acute Cellular Rejection (ACR), which was treated with intravenous methylprednisolone. That evening the patient experienced a 15-minute episode of expressive dysphasia. The following morning she became confused, aphasic, and demonstrated right sided neglect and right hemianopia. A CT cerebral perfusion scan demonstrated hypoperfusion in the left middle cerebral artery (MCA) territory and cerebral angiography revealed widespread, focal multi-segmental narrowing of the anterior and posterior circulations. A diagnosis of RCVS was made, and nimodipine was commenced. As both steroids and tacrolimus are potential triggers of RCVS, cyclosporin replaced tacrolimus and methylprednisolone dose was reduced. A further CTB demonstrated a large left MCA territory infarct with left M2 MCA occlusion. The patient made steady neurological improvement. She was discharged 34 days post-transplantation with mild residual right lower limb weakness and persistent visual field defect on verapamil, cyclosporine, everolimus, mycophenolate mofetil and prednisolone.ConclusionReversible cerebral vasoconstriction syndrome is rare after orthotopic heart transplantation. Until now, RCVS has been almost exclusively described in Asian recipients, and is typically caused by immunotherapy. The condition may lead to permanent neurological deficits, and in the absence of definitive treatments, early recognition and imaging based diagnosis is essential to provide the opportunity to remove the causal agent(s). Co-existent ACR, can pose unique treatment difficulties.

Comparison between Spectral-Domain and Swept-Source OCT Angiography for the Measurement of Persistent Hypertransmission Defects in Age-Related Macular Degeneration

Spectral-domain OCT angiography (SD-OCTA) scans were tested in an algorithm developed for use with swept-source OCT angiography (SS-OCTA) scans to determine if SD-OCTA scans yielded similar results for the detection and measurement of persistent choroidal hypertransmission defects (hyperTDs). Retrospective study. Forty pairs of scans from 32 patients with late-stage nonexudative age-related macular degeneration (AMD). Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6× 6 mm OCTA scan patterns. Using a semiautomatic algorithm that helped with outlining the hyperTDs, 2 graders independently validated persistent hyperTDs, which are defined as having a greatest linear dimension ≥250 μm on the en face images generated using a slab extending from 64 to 400 μm beneath Bruch's membrane. The number of lesions and square root (sqrt) total area of the hyperTDs were obtained from the algorithm using each imaging method. The mean sqrt area measurements and the number of hyperTDs were compared. The number of lesions and sqrt total area of the hyperTDs were highly concordant between the 2 instruments (rc= 0.969 and rc= 0.999, respectively). The mean number of hyperTDs was 4.3 ± 3.1 for SD-OCTA scans and 4.5 ± 3.3 for SS-OCTA scans (P= 0.06). The mean sqrt total area measurements were 1.16 ± 0.64 mm for the SD-OCTA scans and 1.17 ± 0.65 mm for the SS-OCTA scans (P < 0.001). Because of the small standard error of the differences, the mean difference between the scans was statistically significant but not clinically significant. Spectral-domain OCTA scans provide similar results to SS-OCTA scans when used to obtain the number and area measurements of persistent hyperTDs through a semiautomated algorithm previously developed for SS-OCTA. This facilitates the detection of atrophy with a more widely available scan pattern and the longitudinal study of early to late-stage AMD. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Deciphering Alveolo-Capillary Gas Transfer Disturbances in Patients Recovering from COVID-19 Lung Disease.

Impaired lung gas exchange is commonly seen in patients with pulmonary involvement related to SARS-CoV-2 acute infection or post-acute COVID-19 syndrome (PACS). The primary aim of our study was to assess lung gas transfer, measuring the pulmonary diffusion capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) in all COVID-19 patients. Our secondary aim was to decipher the respective roles of perturbed lung membrane conductance (DM) and reduced pulmonary capillary volume (VC) in patients with impaired lung gas exchange. From May to October 2020, we measured DLNO-DLCO in 118 patients during their post-COVID-19 period (4.6 months after infection) to decipher alveolo-capillary gas transfer disturbances. DLNO-DLCO measurement was also performed in 28 healthy non-smokers as controls. Patients were classified into three groups according to the severity (mild, moderate, and severe) of acute COVID-19 infection. Patients with mild COVID-19 had normal lung volumes and airways expiratory flows but impaired pulmonary gas exchange, as shown by the significant decreases in DLNO, DLCO, DM, and VC as compared with controls. VC was significantly impaired and the DLNO/DLCO ratio was increased in patients with moderate (n = 4, 11%) and severe COVID-19 (n = 23, 49%). Abnormal membrane conductance was also seen in all three groups of post-COVID-19 patients. These findings suggest a persistent alveolo-capillary gas transfer defect, implying not only reduced membrane conductance but also abnormal pulmonary vascular capacitance in all PACS patients, even those with a milder form of COVID-19 infection.

The Total Macular Burden of Hyperreflective Foci and the Onset of Persistent Choroidal Hypertransmission Defects in Intermediate AMD

Purpose: The association between the total macular burden of hyperreflective foci (HRF) in eyes with intermediate AMD (iAMD) and the onset of persistent choroidal hypertransmission defects (hyperTDs) was studied using swept-source optical coherence tomography (SS-OCT). DesignPost hoc subgroup analysis of a prospective study. Methods: A retrospective review of iAMD eyes from subjects enrolled in a prospective SS-OCT study was performed. All eyes underwent 6×6 mm SS-OCT angiography (SS-OCTA) imaging at baseline and follow-up visits. En face sub-retinal pigment epithelium (subRPE) slabs with segmentation boundaries positioned 64-400 µm beneath Bruch's membrane (BM) were used to identify persistent choroidal hyperTDs. None of the eyes had persistent hyperTDs at baseline. The same subRPE slab was used to identify choroidal hypotransmission defects (hypoTDs) attributable to HRF located either intraretinally (iHRF) or along the RPE (rpeHRF) based on corresponding B-scans. A semiautomated algorithm was used by two independent graders to validate and refine the HRF outlines. The HRF area and the drusen volume within a 5mm fovea-centered circle were measured at each visit. Results: The median follow-up time for the 171 eyes from 121 patients included in this study was 59.1 months (95%CI: 52.0-67.8 months). Of these, 149 eyes (87%) had HRF, and 82 (48%) developed at least one persistent hyperTD during the follow-up. Although univariable Cox regression analyses showed that both drusen volume and total HRF area were associated with the onset of the first persistent hyperTD, multivariable analysis showed that the area of total HRF was the sole significant predictor for the onset of hyperTDs (P<0.001). ROC analysis identified an HRF area ≥ 0.07 mm² to predict the onset of persistent hyperTDs within one year with an area under the curve (AUC) of 0.661 (0.570-0.753), corresponding to a sensitivity of 55% and a specificity of 74% (P<0.001). Conclusions: The total macular burden of HRF, which includes both the HRF along the RPE and within the retina, is an important predictor of disease progression from iAMD to the onset of persistent hyperTDs and should serve as a key OCT biomarker to select iAMD patients at high-risk for disease progression in future clinical trials.

Incidence and predictors of persistent iatrogenic atrial septal defect following catheter ablation

BackgroundThe left atrium approach for atrial fibrillation (AF) ablation requires an atrial transseptal puncture that may cause an iatrogenic atrial septal defect (iASD). This study aimed to investigate the incidence and predictors of iASD in catheter ablation, assessed by transthoracic echocardiography (TTE), a relatively non-invasive technique frequently employed in follow-up. MethodsThis retrospective study included 639 patients (489 male; 60.2±10.7years) who underwent initial catheter ablation for AF between May 2005 and June 2018. All patients underwent preprocedural transesophageal echocardiography (pre-TEE), preprocedural TTE (pre-TTE), and TTE one day after the procedure (post-TTE). iASD incidence after 6months (6M), preprocedural characteristics, and procedure methods were evaluated. ResultsPatent foramen ovale (PFO) was diagnosed in 42 patients (6.6%) using pre-TEE and in 11 patients using pre-TTE (26.2% of the patients with PFO in pre-TEE). Among the 597 patients without PFO, 497 underwent 6M-TTE. iASD was observed in 59.6% of patients using post-TTE and 4.6% using 6M-TTE. In the univariate logistic regression analysis, the total diameter of the sheath through the septum (odds ratio 1.15, p<0.001) or two sheaths through a single puncture (odds ratio 4.17, p=0.001) were independent risk factors on iASD incidence in 6M-TTE. iASD was also more likely to occur via cryoballoon ablation using a larger sheath than radiofrequency catheter ablation. ConclusionsiASD was not a rare complication. A larger sheath diameter or two sheaths through a single puncture were associated with the incidence of iASD.

40‐4: Improving Visibility Coherence between Auto Macro Inspection and Auto Visual Inspection Using AI Image Translation

In OLED production, the glass fabrication process is prone to frequent occurrences of persistent mura defects, leading to significant damage in the event of defects, as the subsequent final inspection, AVI (Auto Visual Inspection), is time‐consuming. Therefore, there is a need for a consistent inspection. Currently, manual inspection by operators introduces variations in inspection criteria among individuals, resulting in ongoing challenges related to false judgments and post‐process leakage issues The invested automated inspection system for quantitative determination is utilized as a reference only, as the distinction between pseudo‐defects deemed acceptable in AVI and true defects identified as faulty in AVI poses limitations with the traditional logic‐based inspection methods. We enhanced the mura visibility of automatic inspection system (Auto Macro) images through pre‐processing, followed by translation into an image environment similar to AVI images using Pix2pix GAN. Subsequently, we compared the mura index extracted from the processed images with the AVI mura index for evaluation. The Auto Macro images transformed by Pix2pix GAN exhibited similarities with AVI images in terms of overall luminance, gray distribution, and mura visibility intensity. Consequently, the R‐Squared correlation between the mura index of Auto Macro and AVI improved from 0.00 to 0.68. Additionally, defects unrecognized in AVI during Auto Macro inspection were automatically eliminated. False defects in the Auto Macro test that were not recognized in AVI were automatically removed. In this study, we applied the AI model to the Auto Macro inspection system to overcome the limitations of logic‐based inspections. We proposed a method to proactively detect defect‐induced muras before cell‐level processing, aiming to improve yield and reduce incidents of customer leakage accidents.