Myocardial infarction remains a leading cause of heart failure owing to the limited regenerative capacity of adult cardiac tissue, underscoring the need for biomimetic therapeutic platforms that combine structural support with biological functionality. Accordingly, this study aimed to develop a multifunctional electrospun cardiac patch by integrating decellularized neonatal porcine myocardial extracellular matrix (dECM), gelatin, and microbiota-derived postbiotics for cardiac tissue engineering. The fabricated patches were comprehensively characterized in terms of their morphology, mechanical properties, biodegradation behavior, antibacterial activity, antioxidant capacity, and in vitro biocompatibility. Postbiotics derived from Lactiplantibacillus plantarum EIR/IF-1 exhibited potent antimicrobial activity against methicillin-resistant Staphylococcus aureus, strong antioxidant capacity, and significant anti-inflammatory activity through the suppression of pro-inflammatory mediators and upregulation of IL-10 expression. Moreover, they protected H9c2 cardiomyoblasts from oxidative stress, promoted COL1A1 expression, and supported ECM remodeling. The fabricated electrospun cardiac patches exhibited a homogeneous nanofibrous architecture, mechanically suitable properties (Young's modulus ~4 MPa), controlled biodegradation over 7 days, favorable cell viability, and maintained the biological functionality of the incorporated postbiotics. Overall, the synergistic integration of tissue-specific dECM and microbiota-derived postbiotics yielded a multifunctional biohybrid cardiac patch with favorable structural and biological properties, supporting its potential as a promising platform for myocardial regeneration and next-generation cardiac tissue engineering.
Superconducting transmon processors represent a leading platform for large-scale quantum computing due to their high gate fidelities and scalability. However, conventional qubit-coupler-qubit (QCQ) architectures face critical physical and structural bottlenecks, notably frequency crowding [spectator qubit collisions] during system scaling and inefficient mapping onto the standard surface code. To overcome these limitations, we propose a novel lattice-patch architecture that couples four fixed-frequency transmons to a single fixed-frequency coupler. This design enhances qubit connectivity and maps directly onto the surface-code lattice unit [plaquette], thereby minimizing the compilation overhead associated with logical qubit implementation. Furthermore, utilizing an entirely fixed-frequency design intrinsically eliminates susceptibility to external flux noise, ensuring robust operational stability. Multi-level numerical simulations demonstrate CNOT gate fidelities exceeding 0.98 across all six connectivity directions within the patch. Nevertheless, the complex interaction network of the four-qubit architecture induces unintended residual phase accumulation during cross-resonance driving. This parasitic effect necessitates precise calibration, achievable via virtual Rz gates [software phase updates]. Ultimately, our results establish the lattice-patch architecture as an efficient, robust building block for future fault-tolerant quantum computers.
Epicutaneous patch testing is the gold standard for diagnosing allergic contact dermatitis (ACD), yet its interpretation relies on subjective scoring and remains prone to inter-observer variability. In this study, we present a machine learning pipeline that complements subjective scoring with objective bioengineering measurements derived from the Antera 3D imaging system. A dataset of skin reactions was analyzed, with particular attention to how the data was split to avoid information leakage between patients. For this reason, methods such as GroupShuffleSplit and GroupKFold, which account for patient-level clustering, were used. Of the models tested, the Random Forest classifier showed the best overall performance, with an AUC of 0.861 (95% CI: 0.830-0.888) on patient data that had not been used during training, outperforming the Multi-Layer Perceptron model. The incorporation of additional features that capture changes between 48 and 72 h improved the results even further, raising the AUC to 0.902 and achieving a very high sensitivity of 96.8%. Overall, the results show that objective biophysical measurements derived from the Antera 3D imaging system can be combined with machine-learning techniques for objective patch-test assessment. Incorporating temporal changes between the 48- and 72-h readings further improved model performance, suggesting that temporal changes provide additional information beyond single-time-point measurements.
Background: Decellularized extracellular matrix (ECM) patches have emerged as a potential alternative to synthetic and autologous materials in pediatric cardiac surgery; however, clinical data on their use in septal defect repair remain limited. Methods: This single-center retrospective study evaluated the applicability and early outcomes of ECM scaffolds for pediatric septal defect repair using data from the national cardiac surgery registry. Early postoperative outcomes and perioperative variables were analyzed. Results: The study included 72 procedures performed in 68 patients (35 males and 33 females), aged 10 days to 16 years (median age: 187 days; IQR: 105-327 days). Reoperations accounted for 6% of cases. Postoperative complications occurred in 1.4% of patients, and continuous renal replacement therapy was required in 6 (8.8%) patients. Overall mortality was 2.9% (2/68 patients). No statistically significant differences were observed between atrial and ventricular septal defect groups. Conclusions: ECM patches appeared to be a safe and effective option for septal defect repair in pediatric cardiac surgery, demonstrating low complication rates and satisfactory early outcomes across different types of congenital heart defects.
Restoring motor function remains a primary goal in the treatment of spinal cord injury (SCI). However, the inflammatory microenvironment that develops after injury poses a significant barrier to effective neural repair. Addressing this challenge requires the development of bioactive scaffolds with potent anti-inflammatory and antioxidant properties, as well as reduced implantation-induced damage. In this study, we created a novel composite biomaterial scaffold with high mechanical strength and excellent anti-inflammatory and antioxidant capabilities by dispersing in situ self-assembled tea polyphenol-magnesium nanoparticles (TPs-Mg NPs) into gelatin methacryloyl hydrogel (GelMA) microneedle patches (TPs-Mg MN). Our results demonstrate that TPs-Mg MN effectively modulates the inflammatory response by promoting macrophage polarization through suppression of the NF-κB signaling pathway, thereby alleviating reactive oxygen species (ROS)-mediated oxidative damage. Following implantation in a rat SCI model, TPs-Mg MN significantly enhanced motor functional recovery. Behavioral analyses revealed that this recovery was achieved through multiple mechanisms, including reduced oxidative stress, inflammation, and scar formation at the injury site, as well as enhanced angiogenesis and neurogenesis within the spinal cord tissue. This study presents a multifunctional combinatorial strategy for mitigating ROS-induced oxidative stress, offering broad potential applications in SCI and other central nervous system disorders.
Channelrhodopsins have revolutionized the rapid, contactless modulation of action potentials, driving major advances in both neuroscience and cardiac research. In parallel, the automated patch-clamp (APC) technique has emerged as a powerful platform for drug screening. Here, we present the first biophysical characterization of the Na+-selective channelrhodopsin NCR1 2.0 (sharing the rhodopsin part sequences with HcCCR) and the highly Na+/Ca2+-conductive variant XXM 2.0, using APC combined with integrated optical stimulation. These channels are gaining increasing relevance, as Na+- and/or Ca2+-dependent signaling plays pivotal roles in cancer biology and the development of anti-cancer therapeutics. The combined application of optogenetics and APC offers a transformative approach to drug screening, opening new avenues for biomedical innovation. This vision also includes further optical manipulations such as uncaging of substances and molecular photoswitches in photopharmacology, which form synergistic approaches with APC.
Electrical connectors are critical components in electronic systems, and pin-related defects may lead to poor electrical contact, signal transmission failure, and product rejection. Automated inspection of connector pins is therefore essential for ensuring manufacturing quality and reliability. However, collecting and annotating sufficient defective samples remains challenging in industrial environments, limiting the applicability of conventional supervised learning methods. This paper proposes a physics-guided Patch Distribution Modeling (PGPDM) framework for unsupervised electrical connector pin defect detection. Trained exclusively on normal samples, it embeds connector structural priors via ROI masks to filter irrelevant background and focus feature learning on pin defect zones. Multiscale deep features from defect-free samples are utilized to build statistical distributions, and anomalies are detected by measuring feature distribution deviations at inference. Experimental results on a connector pin inspection dataset demonstrate that the proposed approach effectively highlights defective regions and improves detection performance compared with conventional feature-distribution-based anomaly detection methods. The proposed framework provides an accurate, annotation-efficient, and practically deployable solution for industrial connector inspection.
The CAPTRANE trial evaluated the efficacy of randomly assigned high-concentration capsaicin patch (HCCP) versus daily oral pregabalin (PGB) in adults with chronic neuropathic pain (DN4 ≥ 4) post-breast cancer surgery. The objective of its 4-month open-label extension following patient's self-selection of their second treatment (HCCP, PGB, or none) was to explore efficacy and safety of various strategies. The study was conducted in France between March 2019 and November 2022. At each clinic visit, we assessed pain intensity (NRS, 0-10), painful area (cm2), mood (HADS), and quality of life (EQ-5D-5L). Standard statistical tests were used. Data from 116 patients (all females; 76% aged < 65 years) were collected. At Month 2, 71% (46/65) of HCCP-treated patients received a second HCCP application and none switched to PGB, whereas 27% (14/51) continued on PGB and 49% (25/51) of PGB-treated patients switched to HCCP. At Month 6, NRS scores had decreased in HCCP-treated patients, including PGB/HCCP-treated patients, with a reduction of -2.0 [-4.0; 0.0] and -3.0 [-4.0; -2.0] in the HCCP/HCCP and PGB/HCCP group, respectively (median[interquartile]). Adverse events aligned with those expected with HCCP and PGB; none were serious. This first study to examine switching between PGB and HCCP treatments for chronic intercostobrachial neuropathic pain after breast cancer surgery showed patients' preference for HCCP, confirmed the benefit of repeated HCCP applications, and indicated that HCCP could be preceded by PGB without compromising efficacy or safety. These findings suggest that HCCP may be used early in this population, and PGB initiated before HCCP to relieve patients waiting for HCCP application.
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Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are common neurodevelopmental disorders (NDDs) in children and often co-occur (ASD + ADHD), complicating the diagnosis. The diagnostic process is lengthy and subjective, relying heavily on expert knowledge, which limits accessibility. Electroencephalography (EEG) offers potential as a biomarker but requires skilled technicians for measurements and can be stressful for children with NDDs. This study aimed to provide a more accessible diagnostic support tool. We used a portable EEG device with a low participant burden and a deep learning model to distinguish between the typical development group (TD) and the NDD group, comprising children with ASD, ADHD, and ASD + ADHD. Resting-state EEG data were recorded for 5 min using the portable HARU-2 device, which features three channels placed on the forehead of 163 participants (87 TD, 76 NDD). A deep learning model combining a one-dimensional convolutional neural network and a transformer encoder was developed to analyze the EEG data. In 5-fold cross-validation, the model achieved an area under the curve (AUC) of 0.713 and a balanced accuracy (bACC) of 67.5% for classifying NDD and TD. Exploratory evaluation of out-of-fold predictions stratified by clinical phenotype showed an AUC of 0.793 and bACC of 75.0% for ASD vs. TD, 0.817 and 79.5% for ADHD vs. TD, and 0.667 and 62.7% for ASD + ADHD vs. TD. These findings suggest that portable EEG devices combined with deep learning models may serve as accessible adjunctive tools for NDD screening in children.
Transdermal patches are widely used for local anti-inflammatory therapy, but their delivery efficiency is often limited by the barrier function of the stratum corneum. This study aimed to develop an optimized dracorhodin transdermal patch and to evaluate temperature-controlled heating as a physical enhancement strategy using ketoprofen patches as a representative anti-inflammatory model. Dracorhodin ethanol extract was prepared by ethanol extraction and rotary evaporation, and a high-performance liquid chromatography method was established for quantitative analysis. Azone, isopropyl myristate, and acrylate pressure-sensitive adhesive were screened as key excipients, and dracorhodin patches were prepared using a coating method. The optimized patches were evaluated for appearance, content uniformity, adhesion, in vitro skin permeation, and anti-inflammatory activity using an egg white-induced rat paw swelling model. Meanwhile, the effects of heating temperature and heating duration on ketoprofen patch permeation were investigated using in vitro skin permeation experiments, in vivo fluorescence imaging, and pharmacokinetic analysis. The optimized dracorhodin patch formulation contained 19.6% azone, 11.5% isopropyl myristate, and 47.1% pressure-sensitive adhesive. The three batches of patches showed uniform appearance, acceptable content uniformity, stable adhesion, and a cumulative permeation amount of 13-20 μg/cm² within 28 h. In vivo pharmacodynamic evaluation showed that the dracorhodin patch produced a swelling inhibition rate of 62.18% at 4 h, approaching that of the ketoprofen positive control. For ketoprofen patches, temperature-controlled heating significantly enhanced transdermal permeation, with the permeation rate increasing from 10.11 to 20.56 μg/cm²·h as the heating temperature increased from 33°C to 45°C. Heating for 90 min at 40°C provided an effective balance between permeation enhancement and practical application. Fluorescence imaging and pharmacokinetic results further confirmed that thermal treatment improved drug diffusion and systemic exposure. These findings suggest that formulation optimization and temperature-controlled physical enhancement are complementary strategies for improving anti-inflammatory transdermal patch delivery and may provide a basis for the development of advanced patch-based drug-device combination products.
To evaluate the effectiveness of combining patching with active vision therapy, compared to patching with placebo training on contrast sensitivity (CS) in pediatric participants with bilateral refractive amblyopia. In this double-blind, clinical trial, 43 participants aged 5-8 with bilateral refractive amblyopia, unresponsive to spectacles, were randomly assigned to either the experimental group (active vision therapy plus patching) or the control group (placebo treatment with patching) for four months. Active therapy included anti-suppression, accommodative, vergence, and visual memory exercises. CS was measured at baseline and after four months, serving as key outcome measures. Forty participants (20 in each group) completed the study. The mean age for the experimental group (5 males) was 6.10±0.84y, and 6.50±1.15y for the control group (11 males). CS in the experimental group improved by 0.10 log (right eye), 0.14 log (left eye), and 0.07 log binocularly (P≤0.03). The control group showed no statistically significant enhancements in monocular or binocular CS (P≥0.07). Compared to the control group, the experimental group demonstrated a rate of change in monocular CS of 0.05 during follow-up time. Active vision therapy leads to significant and accelerates improvements in CS among children with bilateral refractive amblyopia.
Current artificial intelligence (AI) models for medical imaging predominantly focus on a single imaging modality and a single disease. Attempts to create multimodal and multi-disease models have resulted in inconsistent clinical accuracy. Furthermore, training these models typically requires large, well labelled datasets, which are costly and labour intensive to prepare. We aimed to train and evaluate an AI model that can interpret diverse imaging modalities across specialties while maintaining robust performance within each modality. We developed Multimodal, Multi-Disease Medical Imaging Foundation Model (MerMED-FM), a multi-specialty model trained using self-supervised learning and a memory module. MerMED-FM was pretrained on publicly sourced, unlabelled medical images from 12 specialties and seven imaging modalities: chest x-rays, CT, ultrasound, histopathology, colour fundus photography (CFP), optical coherence tomography (OCT), and dermatoscopy. After pretraining, the model was fine-tuned, validated, and evaluated for the diagnosis of a range of diseases on 26 public datasets and five private datasets comprising radiology, histopathology, and ophthalmology images. MerMED-FM was compared against a general-domain vision foundation model, various specialist single-modality foundation models, and a multispecialty foundation model. Models were fine-tuned using 10%, 30%, 50%, and 100% of data, with primary comparative analyses conducted using a 10% label fraction. The primary outcome was the area under the receiver operating characteristic curve (AUROC), which was summarised by imaging modality. MerMED-FM was trained on around 3·3 million images from 53 publicly available, unlabelled datasets, comprising 713 931 chest x-rays, 292 353 CT slices, 389 885 ultrasound frames, 1 017 712 pathology patches, 333 099 CFP images, 176 719 OCT slices, and 401 059 dermatoscopy images. Strong performance was achieved across all modalities at a label fraction of only 10%, with mean AUROC values of 0·844 for chest x-rays, 0·906 for CT, 0·818 for ultrasound, 0·908 for histopathology, 0·810 for CFP, 0·962 for OCT, and 0·827 for dermatoscopy. MerMED-FM has the potential to be a highly adaptable, versatile, cross-specialty foundation model that enables robust interpretation of medical imaging across diverse medical disciplines. National Medical Research Council, Singapore and the Agency for Science, Technology and Research, Singapore.
This is Part 1 of a 2-part narrative review of contact allergy and allergic contact dermatitis (ACD) to alkyl glucosides. It discusses the nature of alkyl glucosides (mainly decyl, lauryl, cetearyl, and coco-glucoside), their properties and applications, results of patch testing in routine testing and in groups of selected patients, and presents all reported case series and case reports of ACD to decyl and lauryl glucoside. The alkyl glucosides are nonionic surfactants that are produced by the reaction of glucose with fatty alcohols and that are increasingly being used in cosmetics. This class of surfactants and emulsifiers has a low potential for irritation and favorable ecological characteristics, being manufactured from renewable sources and being completely biodegradable. Alkyl glucosides are chemically stable and hardly protein-reactive; they do not contain chemically reactive sites or strongly polarized structures. Therefore, they were not predicted to have allergenic potential. Yet, they can induce contact sensitization, which is increasingly recognized. Currently, decyl glucoside has a rate of 2.4% positive reactions in routine testing in the United States. Most positive patch test reactions have current relevance, in >80% from their presence in personal care products. Part 2 will discuss patient demographics (gender and age, atopic diathesis, distribution of dermatitis, occupational contact dermatitis), products causing ACD, patch test considerations, co-/cross-reactions between alkyl glucosides and nonrelated haptens, and the presence of alkyl glucosides in cosmetics and other products.
Spontaneous phasic contractions (SPCs) in the epididymal duct play an important role in transport and maturation of sperm. In proximal cauda of the rat epididymis, platelet-derived growth factor receptor α (PDGFRα)-positive smooth muscle cells (SMCs) generate ANO1 Ca2+-activated chloride channels (CaCCs)-dependent spontaneous transient inward currents (STICs) to electrically drive SPCs. Here, we explored whether epididymal ANO1+, PDGFRα+ cells may have region-specific functions in generating SPCs. Patch clamp technique was applied to isolated epididymal cells dispersed from the rat epididymis. Membrane potential changes and SPCs were recorded from epididymal tissue preparations using an intracellular microelectrode and video imaging, respectively. To verify ANO1 currents in PDGFRα+ SMCs, patch clamp recordings and immunohistochemistry were performed using PDGFRα-eGFP mice. Rat epididymal cells of both proximal cauda and caput developed spontaneous transient depolarizations (STDs) that were inhibited by Ani9 (3 µM), the ANO1-specific inhibitor, CPA (10 µM), a sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor, or nifedipine (1 µM), an L-type voltage-dependent Ca2+ channel (LVDCC) inhibitor. Ani9 (10 µM) slowed slow waves and associated SPCs in proximal cauda but not the caput. In the mouse epididymis, the proximal cauda consisted of a few layers of SMCs where SMCs in the innermost layer primarily expressed PDGFRα, whereas the caput was composed of one or two layers of PDGFRα+ SMCs. In both regions, Ani9 (3 µM) abolished STICs in PDGFRα+ SMCs that co-expressed ANO1. However, Ani9 (10 µM) slowed SPCs in the proximal cauda but not the caput. Despite the fact that epididymal PDGFRα+ SMCs in both the proximal cauda and caput develop ANO1-dependent STICs, they appear to serve as pacemaker cells driving SPCs in the proximal cauda, whereas corresponding cells in the caput have a role other than SPCs' pacemaking.
Epoxy resin systems (ERS) frequently cause occupational allergic contact dermatitis. To analyze and update sensitization frequencies to epoxy resin, reactive diluents and hardeners in patients with occupational dermatitis (OD). Retrospective descriptive and comparative analysis of data collected by the Information Network of Departments of Dermatology (IVDK) from OD patients patch tested with bisphenol A diglycidyl ether (DGEBA) epoxy resin, 2008-2022. DGEBA sensitization declined overall, with fluctuations, from 4.2% in 2008-2010 to 2.9% in 2020-2022 (p = 0.0014). Adjusted odds ratios (ORs) were highest for plastics processors (11.7; 95% CI, 8.1-16.6), bricklayers, cement and concrete workers (6.4; 5.1-8.0), and painters/varnishers (5.3; 4.0-6.9). DGEBA-positive patients were most frequently co-sensitised to the reactive diluents 1,6-hexanediol diglycidyl ether (43.6%), 1,4-butanediol diglycidyl ether (35.7%), and phenyl glycidyl ether (30.8%), and to the hardener m-xylylenediamine (22.7%). DGEBA testing alone would not have identified 446 patients (1.9% of all DGEBA-tested OD patients) with sensitizations to reactive diluents or amine hardeners. If contact allergy to ERS components is suspected, not only DGEBA, but also reactive diluents and hardeners should be patch tested. Prevention should prioritise exposure control, occupational hygiene, ongoing surveillance, and periodic test series updates.
Preoperative implant planning based on cone-beam computed tomography (CBCT) images supports prosthetically driven treatment but remains time-consuming and experience-dependent. This study developed and evaluated ImplantPlanNet, an automatic initial implant planning framework for single-tooth missing scenarios. ImplantPlanNet incorporates candidate localization, local patch extraction, pose estimation from local patches, and geometric parameter recovery to estimate implant position, implant long-axis direction, length, and diameter. A dataset of 144 preoperative CBCT images from single-tooth missing sites was divided into training (n=104), internal testing (n=20), and external testing (n=20) sets. ImplantPlanNet-predicted implant plans were compared with specialist reference implant plans using three-dimensional (3D) coronal deviation, 3D apical deviation, angular deviation, dimension classification accuracy, and safety-related distance measurements. Internal 3D coronal and 3D apical deviations were 1.53 ± 0.80 mm and 1.77 ± 0.82 mm, respectively, with an angular deviation of 5.55 ±3.39°. Corresponding external values were 1.67 ± 1.74 mm, 2.21 ± 1.66 mm, and 6.92 ±3.41°. Length classification accuracy was 65.0% in both sets; diameter classification accuracy was 100.0% internally and 75.0% externally. Safety-related distance measurements were generally comparable between ImplantPlanNet-predicted and reference implant plans, except for a slight reduction in buccal bone plate thickness in the external testing set. The findings support the feasibility of using ImplantPlanNet to generate automatic initial implant plans from preoperative CBCT images for clinician review in single-tooth missing scenarios. ImplantPlanNet may support clinician-supervised CBCT-based initial implant planning by generating proposals for single-tooth missing scenarios.
Topical medications are commonly used to manage mild-to-moderate psoriasis as adjunctive treatments in patients receiving phototherapy, systemic agents or biologic therapies. Amongst available topical options, the fixed-dose combination of calcipotriol (CAL) and betamethasone dipropionate (BDP) has demonstrated efficacy and tolerability in clinical trials, with most adverse events being mild and transient local reactions. CAL/BDP has recently been formulated as a cream using polyaphron dispersion (PAD) technology to improve its rheological behaviour and sensory characteristics. We describe the use of CAL/BDP PAD-based cream specifically in patients with mild-to-moderate psoriasis across four Italian centres. The first case involves a man with mild-to-moderate scalp psoriasis, in whom CAL/BDP PAD-based cream was effective in this high-impact disease location. The second case focuses on a patient with pretibial psoriasis, a difficult-to-treat site. The third case is of a woman with palmoplantar psoriasis who reported clinical improvement in the lesions and increased treatment compliance compared with her previous therapies. The last case describes the concomitant use of CAL/BDP PAD-based cream with a biologic drug, resulting in optimized lesion clearance. CAL/BDP PAD-based cream appears promising for managing psoriasis in specific contexts such as lesions in difficult-to-treat areas or residual disease during biologic therapy. Further real-world data and clinical observations will be important to clarify how this formulation can be integrated into individualized management strategies for mild-to-moderate psoriasis. Psoriasis is a disease that causes red, scaly patches in the skin on many parts of the body, causing discomfort, itching and pain. Creams and ointments are the first treatment for people with psoriasis that causes small or noticeable discomfort (mild-to-moderate psoriasis). One of the available creams combines calcipotriol and betamethasone dipropionate (CAL/BDP) in a formulation called polyaphron dispersion (PAD). This article describes the experiences of four Italian people who used a CAL/BDP PAD-based cream to manage their psoriasis. The first was a man with scalp psoriasis and on many other body parts. After using the cream, his red, scaly patches cleared. The second was a patient with psoriasis on the shin, an area that is often difficult to treat. In this case as well, the signs on the skin disappeared. The third patient was a woman with psoriasis on her palms and soles, another challenging location of the disease. Her skin improved, and she found the cream easier to use compared with treatments she had tried before. The last case describes a patient who used the cream in combination with a biologic drug and achieved better skin clearance than when he used the biologic drug alone. In the cases presented, this product helps manage mild-to-moderate psoriasis, even in difficult-to-treat areas of the body. However, four examples are not enough to gain a general conclusion although they provide insights into the use of CAL/BDP PAD-based cream in people with psoriasis.
Background. Iodinated contrast media (ICM) are widely used and generally safe, although hypersensitivity reactions (HSR) may occur. This study aimed to characterize the allergological workup of patients with suspected ICM HSR and evaluate outcomes after re-exposure. Methods. We conducted a unicentric  retrospective study of patients referred between January 2012 and December 2024 for suspected ICM HSR. Diagnosis was confirmed by suggestive clinical history (CH) with positive skin tests (skin prick, intradermal, and/or patch tests), with or without positive basophil activation test (BAT) or lymphocyte transformation test (LTT), or by a positive drug provocation test (DPT). Diagnosis was considered probable with suggestive CH and positive BAT/LTT, and excluded after negative DPT. Clinical records were reviewed, and patients were contacted to assess re-exposure outcomes. Results. A total of 129 patients were included (57% female; mean age 59 ± 15 years); 10% were atopic. Iopromide was the most frequently suspected agent (66%). Reactions were immediate in 67% and non-immediate in 33%, mainly cutaneous (67%). Among those completing the workup (n = 94), immediate HSR was excluded in 40 patients and confirmed in 22 (NPV 77%). Non-immediate HSR was confirmed in 18, considered probable in 3, and excluded in 10; intradermal and patch tests NPV was 44%. Among 40 patients with confirmed HSR, three were re-exposed to the culprit ICM and two reacted. Of 51 patients with excluded HSR, 25 were re-exposed, with one mild reaction. Conclusions. CH alone overestimates ICM HSR. Diagnosis relies on skin tests and particularly DPT, which supported exclusion of HSR, when negative.
Diffuse plane xanthoma (DPX) is a distinctive and rare dermatologic condition that can signal an underlying, usually hematologic, often malignant condition, including multiple myeloma, monoclonal gammopathy, diffuse histiocytic lymphoma, acute monoblastic leukemia, chronic myelomonocytic leukemia, chronic myeloid leukemia, chronic lymphatic leukemia, adult T-cell lymphoma/leukemia, Sezary syndrome, Waldenstrom's macroglobulinemia, non-Hodgkin's lymphoma, cryoglobulinemia, and Castleman's disease. DPX is clinically characterized by nonpruritic flat, yellowish macules/patches predominantly affecting the face, neck, and upper portion of the body; Histologically, there are lipid-laden macrophages in the dermis that immunohistochemically reveal positive staining for macrophage markers with negative staining for lipid-specific markers. While there is no specific treatment for DPX, treatment of the underlying condition generally reduces or resolves the clinical appearance of the xanthomas.