In Situ Patch Test and Repeated Open Application Test for Fixed Drug Eruption: A Multicenter Study.

BACKGROUND: Few studies have evaluated allergy workup in fixed drug eruption (FDE) in a large population. OBJECTIVE: To evaluate the sensitivity of a standardized allergy workup for diagnosing the cause of FDE, with a focus on in situ repeated open application tests (ROATs). METHODS: In a retrospective multicenter study, we analyzed the practice of conducting a complete allergy workup for the etiological diagnosis of FDE. It consisted of 3 steps: in situ patch tests (PTs) for all cases except pure mucosal involvement, followed by in situ ROAT if in situ PT results were negative, and finally a drug challenge (DC). The in situ ROAT involved daily application of the suspected drug on a previously affected FDE site for 7 days. RESULTS: Of 98 suspected FDE cases, 61 patients (median age 61 y; male-to-female ratio 1.8) with a complete allergy workup were included. In 4 cases, even the DC yielded negative results. Among the remaining 57 patients with a positive workup, implicated drugs included paracetamol (12 cases), ß-lactams (11 cases), imidazoles (9 cases, including 5 with metronidazole), nonsteroidal anti-inflammatory drugs (8 cases), iodinated contrast media (4 cases), cotrimoxazole (3 cases), and various other drugs in 10 patients. The diagnosis was confirmed by in situ PT in 17 of 54 cases (31.5%), in situ ROAT in 14 of 40 cases (35%) (with 4 cases showing remote reactivation of FDE sites), and DC in 26 cases. CONCLUSIONS: The sequential allergy workup involving successively in situ PT, in situ ROAT, and DC is a reliable and safe method for diagnosing the cause of FDE. In situ tests exhibited a sensitivity of over 50%.

Advanced Detection Method for Dengue NS1 Protein Using Ultrasensitive ELISA with Thio-NAD Cycling.

Dengue fever, a mosquito-borne disease in tropical and subtropical climates caused by the dengue virus (DENV), has become a major social and economic burden in recent years. However, current primary detection methods are inadequate for early diagnosis of DENV because they are either time-consuming, expensive, or require training. Non-structural protein 1 (NS1) is secreted during DENV infection and is thus considered a suitable biomarker for the development of an early detection method. In the present study, we developed a detection method for the NS1 protein based on a previously reported thio-NAD cycling ELISA (i.e., ultrasensitive ELISA) and successfully achieved a LOD of 1.152 pg/mL. The clinical diagnosis potential of the detection system was also evaluated by using 85 patient specimens, inclusive of 60 DENV-positive and 25 DENV-negative specimens confirmed by the NAAT method. The results revealed 98.3% (59/60) sensitivity and 100% (25/25) specificity, which was in almost perfect agreement with the NAAT data with a kappa coefficient of 0.972. The present study demonstrates the diagnostic potential of using an ultrasensitive ELISA as a low-cost, easy-to-use method for the detection of DENV compared with NAAT and could be of great benefit in low-income countries.

Path Generation Strategy and Wire Arc Additive Manufacturing of Large Aviation Die with Complex Gradient Structure.

To realize automatic wire arc additive manufacturing (WAAM) of a large aviation die with a complex gradient structure, a new contour-parallel path generation strategy was proposed and practically applied. First, the planar curve was defined as a vertical slice of a higher-dimensional surface and a partial differential equation describing boundary evolution was derived to calculate the surface. The improved Finite Element Method (FEM) and Finite Difference Method (FDM) were used to solve this partial differential equation. Second, a cross section of a large aviation die was used to test the path-generation algorithms. The results show that FEM has a faster solving speed than FDM under the same solving accuracy because the solving domain of FEM mesh was greatly reduced and the boundary mesh could be refined. Third, the die was divided into three layers: base layer, transition layer (Fe-based material) and strengthening layer (Co-based material) according to the difference of the temperature and stress field, and corresponding WAAM process parameters has been discussed. The optimum welding parameters are obtained as follows: voltage is 28 V, wire feeding speed is 8000 mm/min and welding speed is 450 mm/min. Finally, the path generation strategy was practically applied to the remanufacture of the large aircraft landing gear die with a three-layer structure. The application test on aircraft landing gear dies justified the effectiveness of the algorithms and strategy proposed in this paper, which significantly improved the efficiency of the WAAM process and the service life of large aviation dies with complex gradient structures. The microstructure of the fusion zone shows that the base metal and welding material can be fully integrated into the welding process.

What is the optimal duration for a ROAT? The experience of the French Dermatology and Allergology group (DAG).

BACKGROUND AND OBJECTIVES: The repeated open application test (ROAT) is an adjuvant investigation measure to patch testing in the diagnosis of allergic contact dermatitis. ESCD recommends a 15 days duration but its overall duration varies according to publications and patients hardly adhere to prolonged ROAT duration beyond 1 week. MATERIALS AND METHODS: The Dermatology and Allergy Group of the French Society of Dermatology performed a prospective study with the aim of determining the best duration for the ROAT. RESULTS: A total of 328 ROAT results were collected for topical products, including cosmetics (60%) and topical medications (31.1%). Fifty-nine (18%) ROATs were positive, and 16 (5%) were doubtful. All the positive ROATs occurred within 10 days, with a median time to positivity of 3 days. CONCLUSION: According to our results, a minimum duration of 10 days is necessary to achieve a positive ROAT to a topical product.

Clinical relevance of positive patch test reactions to lanolin: A ROAT study.

BACKGROUND: Lanolin is often included when patch testing for common contact allergens. The clinical relevance of a positive patch test reaction to lanolin markers is, however, still a subject for debate. OBJECTIVES: To evaluate Amerchol L101 as a marker of lanolin allergy and investigate the clinical impact of lanolin-containing moisturizers on healthy and damaged skin using the repeated open application test (ROAT). METHODS: Twelve test subjects and 14 controls were patch tested with Amerchol L 101 and additional lanolin markers. Subsequently, a blinded ROAT was performed on the arms of the study participants for 4 weeks. Each participant applied a lanolin-free cream base and two different lanolin-containing test creams twice daily on one arm with intact skin and on the other arm with irritant dermatitis, induced by sodium lauryl sulfate (SLS). RESULTS: Eleven test subjects (92%) had positive patch test reactions to Amerchol L 101 when retested and one test subject (8%) had a doubtful reaction. None of the study participants had any skin reactions to the ROAT on intact skin and all participants healed during the ROAT on damaged skin. CONCLUSIONS: Lanolin-containing emollients do not cause or worsen existing dermatitis when performing ROAT in volunteers patch test positive to Amerchol L101.

Artificial intelligence CT screening model for thyroid-associated ophthalmopathy and tests under clinical conditions.

PURPOSE: Thyroid-associated ophthalmopathy (TAO) might lead to blindness and orbital deformity. The early diagnosis and treatment are conducive to control disease progression, but currently, there is no effective screening method. The present study aimed to introduce an artificial intelligence (AI) model for screening and testing the model with TAO patients under clinical conditions. METHODS: A total of 1435 computed tomography (CT) scans were obtained from the hospital. These CT scans were preprocessed by resampling and extracting the region of interest. CT from 193 TAO patients and 715 healthy individuals were adopted for three-dimensional (3D)-ResNet model training, and 49 TAO patients and 178 healthy people were adopted for external verification. Data from 150 TAO patients and 150 healthy people were utilized for application tests under clinical conditions, including non-inferiority experiments and diagnostic tests, respectively. RESULTS: In the external verification of the model, the area under the receiver operating characteristic (ROC) curve (AUC) was 0.919, indicating a satisfactory classification effect. The accuracy, sensitivity, and specificity were 0.87, 088, and 0.85, respectively. In non-inferiority experiments: the accuracy was 85.67% in the AI group and 84.33% in the resident group. The model passed both non-inferiority experiments (p = 0.001) and diagnostic test (the AI group sensitivity = 0.87 and specificity = 0.84%). CONCLUSIONS: A promising orbital CT-based TAO screening AI model was established and passed application tests under clinical conditions. This may provide a new TAO screening tool with further validation.

[Diagnosis of contact allergy in practice using current guidelines]. / Leitliniengerechte Diagnostik der Kontaktallergie in der Praxis.

BACKGROUND: In the case of a contact allergy, there is only allergen avoidance instead of causal therapy. If the allergen is not identified, dermatitis persists, which is a major burden for patients. Patch testing is the diagnostic standard for detecting contact sensitization. Based on a systematic literature search, the German patch test guideline was updated and methodologically upgraded. OBJECTIVES: The most important practical aspects of patch testing with contact allergens and drugs are presented. MATERIALS AND METHODS: Current consensus guidelines for performing patch tests as well as the results of a supplementary selective literature search are summarized. RESULTS: According to the patch test guideline (AWMF registry no. 013-018, 2019), the baseline series, special series and, if necessary, test preparations prepared from the patient's own contact substances should be tested routinely. A new evidence-based recommendation is a late reading after 7-10 days, as otherwise numerous patch test reactions will be missed. Antihistamines may weaken the cellular reactions of the patch test and should be discontinued with a latency of 5 half-lives. Finally, if a false-negative patch test result is suspected, it is recommended to perform a strip patch test according to the validated protocol. CONCLUSIONS: All patients with a suspected contact allergy should receive a guideline-based patch test at an early stage. Targeted patch testing identifies clinically relevant allergens and provides suggestions for further systematic investigations.

Comparison of Two pH Responsive Color Changing Bio-Based Films Containing Wasted Fruit Pomace as a Source of Colorants.

The main objective of this work is to develop and characterize novel bio-based sensor as intelligent food packaging film to monitor quality changes in fresh chicken meat. Chitosan (CS) and carboxymethyl cellulose (CMC) were used as polymer matrices for immobilization of pH sensitive color indicators. Generally considered as a food waste, blueberry (BP) and red grape skin pomace (RP) extracts were used as indicators at total phenolic content (TPC) of 0.06, 0.13, and 0.25 w/v for BP, and 0.006, 0.012, and 0.02 w/v for RP-based films. Color, mechanical, and intelligent material properties were determined. CS films were more elastic than CMC, while no significant changes in mechanical properties occurred after the addition of both extracts at all concentrations. Notable and eye recognizable color changes in dry films were seen. It was the most significant in the pH range from 4 to 7. For CMC-based films, color changed from violet to pink for BP extracts and from red to pink for RP extracts. For CS films, the changes were less significant. The color taint and intensity changed toward green in blueberry-based films and to orange in grape seed extract-based films. Significant color changes were observed after 46 hr in application tests on fresh chicken meat. This was correlated to pH changes of meat above 6 that was one of the parameters considered as an indication of spoilage. PRACTICAL APPLICATION: This work provides interesting data to food industry. It offers an idea and possibility of managing food waste from fruits and vegetables industry that makes problems and costs when needed to be disposed in a proper manner. Moreover, there is the possibility of producing novel kind of food packaging materials that could be used in order to check the end of food shelf-life in an inexpensive and natural way. Additional value lies in the fact that materials and procedures could be considered as sustainable.

Effects of different base agents on prediction of skin irritation by sodium lauryl sulfate using patch testing and repeated application test.

Animal testing for cosmetics was banned in the European Union (EU) in 2013; therefore, human tests to predict and ensure skin safety such as the patch test or usage test are now in demand in Japan as well as in the EU. In order to investigate the effects of different bases on the findings of tests to predict skin irritation, we performed patch testing (PT) and the repeated application test (RAT) using sodium lauryl sulfate (SLS), a well-known irritant, dissolved in 6 different base agents to examine the effects of these bases on skin irritation by SLS. The bases for PT were distilled water, 50% ethanol, 100% ethanol, a gel containing 50% ethanol, white petrolatum, and hydrophilic cream. The concentrations of SLS were 0.2% and 0.5%. Twelve different base combinations were applied to the normal back skin of 19 individuals for 24h. RAT was performed with distilled water, 50% ethanol, 100% ethanol, a gel containing 50% ethanol, white petrolatum, and hydrophilic cream containing SLS at concentrations of 0.2%, 2%, and 5%, being applied to the arms of the same PT subjects. The test preparation of each base was applied at the same site, with 0.2% SLS being used in the first week, 2% SLS in the following week, and 5% SLS in the final week. The results of PT revealed that skin irritation scores varied when SLS at the same concentration was dissolved in a different base. The results of RAT showed that although skin irritation appeared with every base at a concentration of 5%, the positive rate was approximately the same. In conclusion, our results suggest that skin irritation elicited in PT depends on the base, while in RAT, it does not depend on the type of base employed.

Optimal evaluation time point for patch testing to predict skin irritation of commercial topical drugs.

To develop patch testing (PT) that better reflects the skin irritation resulting from repeated applications, we methodically classified PT results and examined correlations between these results with results from repeated application tests. A total of 115 commercial topical drugs were used for patch testing. In two groups of 30 healthy individuals with normal back skin, 55 or 60 commercial topical drugs were applied to the back for 24 h. Skin reactions were scored for each group at 2 and 24 h after patch removal. Based on time-dependent changes in skin reaction at each evaluation time, PT results were classified into six different types. For repeated application testing, a total of 17 products with different types of PT results were selected. A total of 104 healthy individuals divided into three groups (n = 22-52 each) received application of 6-7 test materials, differing for each group, for 3 weeks on both arms. Incidences of positive symptoms induced by repeated drug application excluding transient erythema showed a greater correlation with reaction levels at 24 h after patch removal than 2 h after patch removal. Many test materials that triggered a high incidence of positive symptoms after repeated application also exhibited erythema or greater reaction up to 24 h after patch removal. PT offers a useful test system for predicting skin irritation that develops after repeated application of topical drug. Moreover, assessment at 24 h after patch removal is suggested as the optimal evaluation time point to reflect the results of repeated application tests.