Delayed hypersensitivity reactions to iodinated contrast media: A diagnostic approach by skin tests.

BACKGROUND: Adverse drug reactions to iodinated contrast media (ICM) have risen due to their increasing use in x-ray-based imaging modalities. Delayed hypersensitivity reactions are mainly caused by nonionic monomeric compounds and represent an issue impacting the diagnostic-therapeutic pathways of cancer, cardiology and surgery patients. OBJECTIVES: To prospectively evaluate the usefulness of skin tests in delayed hypersensitivity reactions to ICM and to evaluate the tolerability of iobitridol, a monomeric nonionic low osmolality compound, as a possible safe alternative. METHODS: Patients with delayed hypersensitivity reactions to ICM referred to us from 2020 to 2022 were prospectively enrolled in the study. All patients underwent patch test and, if negative, intradermal test with the culprit ICM and iobitridol as alternative. RESULTS: A total of 37 patients (females 24, 64.9%) were enrolled in the study. Iodixanol and iomeprol were the most frequently involved ICM (48.5% and 35.2%, respectively); 62.2% of patients presented maculopapular eruption, while 37.8% reported delayed urticaria-like rash. Skin tests resulted positive to the culprit ICM in 19 patients (51.4%), 16 to patch test and 3 to intradermal test. Skin tests with iobitridol, tested as alternative, resulted positive in 3/19 patients (15.8%). All 16 patients with negative results to iobitridol were administered this ICM and tolerated it. CONCLUSIONS: In at least half of patients, delayed-type hypersensitivity was demonstrated by skin tests, particularly by patch test. This diagnostic approach resulted simple, cost-effective and safe, not only to confirm the culprit ICM but also to identify iobitridol as feasible alternative.

Contact allergy to hydroxyisohexyl 3-cyclohexene carboxaldehyde in Italy: Prevalence, trend, and concordance with fragrance mix II.

BACKGROUND: Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC), contained in fragrance mix II (FM II), has been recognized as a contact sensitizer since the mid-1990s. After several attempts to reduce its use during the last two decades, HICC was permanently banned from the European market in August 2021. OBJECTIVES: To assess the prevalence and the time trend of contact allergy to HICC and to investigate the concordance of HICC allergy compared to FM II allergy in an unselected Italian patch test population. METHODS/PATIENTS: Retrospective analysis on demographics and patch test results of HICC-sensitized and/or FM II-sensitized patients was performed over a 6-year period (2016-2021) at 6 patch test Clinics in Italy. RESULTS: Among 7266 patients (4942 females, 68.0%, mean age 45.4 ± 20.6 years), 1% (70) resulted positive to HICC and 2.1% (153) to FM II. Clinical relevance was documented in 72.9% (51/70) of HICC positive patients. Among the 169 HICC and/or FM II positive patients, 9.5% had a positive reaction to HICC only, 31.9% to both HICC and FM II, and 58.6% to FM II only. The prevalence trend line of HICC positive reactions showed a decrease from 1.15% (2016) to 0.96% (2021). CONCLUSIONS: We documented a decreasing trend of HICC allergy in Italy, in line with the data recently reported in literature. Nevertheless, HICC should be maintained in the baseline series to monitor the benefits of its ban from the European market.

Measurement of Thermal Conductivity and Thermal Diffusivity of Porcine and Bovine Kidney Tissues at Supraphysiological Temperatures up to 93 °C.

This experimental study aimed to characterize the thermal properties of ex vivo porcine and bovine kidney tissues in steady-state heat transfer conditions in a wider thermal interval (23.2-92.8 °C) compared to previous investigations limited to 45 °C. Thermal properties, namely thermal conductivity (k) and thermal diffusivity (α), were measured in a temperature-controlled environment using a dual-needle probe connected to a commercial thermal property analyzer, using the transient hot-wire technique. The estimation of measurement uncertainty was performed along with the assessment of regression models describing the trend of measured quantities as a function of temperature to be used in simulations involving heat transfer in kidney tissue. A direct comparison of the thermal properties of the same tissue from two different species, i.e., porcine and bovine kidney tissues, with the same experimental transient hot-wire technique, was conducted to provide indications on the possible inter-species variabilities of k and α at different selected temperatures. Exponential fitting curves were selected to interpolate the measured values for both porcine and bovine kidney tissues, for both k and α. The results show that the k and α values of the tissues remained rather constant from room temperature up to the onset of water evaporation, and a more marked increase was observed afterward. Indeed, at the highest investigated temperatures, i.e., 90.0-92.8 °C, the average k values were subject to 1.2- and 1.3-fold increases, compared to their nominal values at room temperature, in porcine and bovine kidney tissue, respectively. Moreover, at 90.0-92.8 °C, 1.4- and 1.2-fold increases in the average values of α, compared to baseline values, were observed for porcine and bovine kidney tissue, respectively. No statistically significant differences were found between the thermal properties of porcine and bovine kidney tissues at the same selected tissue temperatures despite their anatomical and structural differences. The provided quantitative values and best-fit regression models can be used to enhance the accuracy of the prediction capability of numerical models of thermal therapies. Furthermore, this study may provide insights into the refinement of protocols for the realization of tissue-mimicking phantoms and the choice of tissue models for bioheat transfer studies in experimental laboratories.

Thermophysical and mechanical properties of biological tissues as a function of temperature: a systematic literature review.

BACKGROUND: Detailed information on the temperature dependence of tissue thermophysical and mechanical properties is pivotal for the optimal implementation of mathematical models and simulation-based tools for the pre-planning of thermal ablation therapies. These models require in-depth knowledge of the temperature sensitivity of these properties and other influential terms (e.g., blood perfusion and metabolic heat) to maximize the treatment prediction outcome. METHODOLOGY: A systematic literature review of experimental trials investigating thermophysical and mechanical properties of biological media, as well as blood perfusion and metabolic heat, as a function of temperature in hyperthermic and ablative thermal range, was conducted up to June 2021. RESULTS: A total of 61 articles was selected, thus enabling a comprehensive overview of the temperature dependence of thermophysical properties (i.e. thermal conductivity, specific heat, volumetric heat capacity, density, thermal diffusivity), and mechanical properties (shear, elastic, storage, loss and complex moduli, loss factor, stiffness) along with the principal measurement techniques. The reviewed studies considered different tissues, e.g., liver, fat, cartilage, brain, myocardium, muscle, bone, skin, pancreas tissues, and also some tumorous tissues. CONCLUSIONS: The thermophysical properties of soft tissues appear rather constant until 90 °C, with slight differences ascribable to tissues characteristics and measurement methods. Conversely, the information on mechanical properties is heterogeneous because most of the articles investigated different types of properties in different biological tissues. Furthermore, most of the experiments were conducted ex vivo; only a small percentage concerned in vivo studies. Limited recent information about the temperature dependence of metabolic heat and blood perfusion was observed.

Effectiveness and safety of lidocaine patch 5% to treat herpes zoster acute neuralgia and to prevent postherpetic neuralgia.

Herpes zoster is often associated to acute neuralgia and postherpetic neuralgia (PHN). Their therapeutic management is still challenging: among therapeutic options, lidocaine patch 5% was rarely used in acute neuralgia on lesional skin, and its efficacy to prevent PHN was never studied. The efficacy and tolerability of lidocaine patch 5% was evaluated in 38 patients with acute neuralgia (19) and PHN (19). Pain intensity was investigated using DN4 questionnaire and NRS-11 scale at baseline and at week 2, 4, and 8. The use of rescue therapy was also evaluated. A significant reduction of DN4 and NRS-11 was observed already at W2, with further improvement at W4 and W8. A complete response to treatment (DN4 and NRS-11 = 0) at week 8 was higher in patients with acute neuralgia (63.2%) than PHN (31.6%). Rescue therapy gradually decreased in acute neuralgia patients from week 2 (57.9%) to week 8 (10.5%), with only two patients needing neuroleptics. In PHN patients rescue therapy remained stable (68.4%). According to our results, lidocaine patch 5% applied on lesional skin was well tolerated and ensured a rapid pain relief in acute neuralgia; if early used, it prevented PHN in almost all patients.

DECISA Project (DErmatology Clinics in Italy: Survey on Alitretinoin): A real-life retrospective cohort multicenter study on 438 subjects with chronic hand eczema.

Alitretinoin is the only systemic agent approved to treat moderate-severe chronic hand eczema (CHE) unresponsive to potent topical corticosteroids. No nationwide Italian data regarding real-life efficacy, safety, and tolerability of treatment are available. The DECISA project (DErmatology Clinics in Italy: Survey on Alitretinoin) retrospectively examined data from a registry including 15 Dermatology Clinics authorized to prescription of alitretinoin for CHE patients. Disease severity was assessed at baseline, and after 3 and 6 months of treatment, using the 5-point Physician Global Assessment (PGA) and the modified Total Lesion-Symptoms-Severity (mTLSS) scores. Between November 2010 and July 2018, data of 248 male and 190 female patients (mean age 49.71 ± 13.20 years) treated with alitretinoin were collected. Of them, 43.2% had irritant contact dermatitis, 22.2% allergic contact dermatitis, 18.0% atopic dermatitis, 16.7% mixed (irritant/allergic) type of eczema. At 3 months, the 420 re-evaluated patients showed significantly reduced mTLSS and PGA (P < .0000001 vs baseline for both); PGA was clear/almost clear in 35.6% of cases. At 6 months, the 341 re-evaluated patients showed significant (P < .0000001) improvement of mTLSS and PGA vs baseline and 3 months (PGA clear/almost clear: 41.4%). Relapses occurred in 125 patients; 58 underwent an additional course of alitretinoin, with similarly good results. No relevant safety issues were reported; 86 patients experienced adverse effects, which forced 40 to prematurely stop treatment. The DECISA project results confirm the real-life efficacy, safety and tolerability of alitretinoin in the treatment of moderate to severe CHE refractory to standard topical therapies.

Thermal analysis of laser irradiation-gold nanorod combinations at 808 nm, 940 nm, 975 nm and 1064 nm wavelengths in breast cancer model.

BACKGROUND: Photothermal therapy is currently under the spotlight to improve the efficacy of minimally invasive thermal treatment of solid tumors. The interplay of several factors including the radiation wavelengths and the nanoparticle characteristics underlie the thermal outcome. However, a quantitative thermal analysis in in vivo models embedding nanoparticles and under different near-infrared (NIR) wavelengths is missing. PURPOSE: We evaluate the thermal effects induced by different combinations of NIR laser wavelengths and gold nanorods (GNRs) in breast cancer tumor models in mice. MATERIALS AND METHODS: Four laser wavelengths within the therapeutic window, i.e., 808, 940, 975, and 1064 nm were employed, and corresponding GNRs were intratumorally injected. The tissue thermal response was evaluated in terms of temperature profile and time constants, considering the step response of a first-order system as a model. RESULTS: The 808 nm and 1064 nm lasers experienced the highest temperature enhancements (>24%) in presence of GNRs compared to controls; conversely, 975 nm and 940 nm lasers showed high temperatures in controls due to significant tissue absorption and the lowest temperature difference with and without GNRs (temperature enhancement <10%). The presence of GNRs resulted in small time constants, thus quicker laser-induced thermal response (from 67 s to 33 s at 808 nm). CONCLUSIONS: The thermal responses of different GNR-laser wavelength combinations quantitatively validate the widespread usage of 808 nm laser for nanoparticle-assisted photothermal procedures. Moreover, our results provide insights on other usable wavelengths, toward the identification of an effective photothermal treatment strategy for the removal of focal malignancies.

Patch testing of budesonide in Italy: The SIDAPA baseline series experience, 2018-2019.

BACKGROUND: Budesonide was included in the European Baseline Series in 2000 as the most suitable marker forcorticosteroid hypersensitivity. In the last two decades, a decreasing trend of budesonide allergy has been observed. OBJECTIVES: To estimate the prevalence of positive patch test reactions to budesonide in a large, Italian patch test population, characterizing patients according to MOAHLFA index and evaluating the benefit with extended readings of budesonide patch test. METHODS: Retrospective analysis of patient demographics and patch test results over a 2-year period (2018-2019) was performed at 14 patch test clinics in Italy. RESULTS: Ninety out of 14 544 (0.6%) patients reacted to budesonide 0.01% pet.. Positive reactions were mild in 54.4% and late readings at day 7 showed new positive reactions in 37.8% of patients. The MOAHLFA index showed a significant positive association with male gender, atopic dermatitis, and age >40 years and a significant negative association with hand and face dermatitis. CONCLUSIONS: We documented a low prevalence of budesonide allergy in Italy, confirming its decreasing trend recently reported in the literature. Nevertheless, budesonide needs to be maintained in the baseline series for its good ability to detect corticosteroid sensitization.

Measurement of Ex Vivo Liver, Brain and Pancreas Thermal Properties as Function of Temperature.

The ability to predict heat transfer during hyperthermal and ablative techniques for cancer treatment relies on understanding the thermal properties of biological tissue. In this work, the thermal properties of ex vivo liver, pancreas and brain tissues are reported as a function of temperature. The thermal diffusivity, thermal conductivity and volumetric heat capacity of these tissues were measured in the temperature range from 22 to around 97 °C. Concerning the pancreas, a phase change occurred around 45 °C; therefore, its thermal properties were investigated only until this temperature. Results indicate that the thermal properties of the liver and brain have a non-linear relationship with temperature in the investigated range. In these tissues, the thermal properties were almost constant until 60 to 70 °C and then gradually changed until 92 °C. In particular, the thermal conductivity increased by 100% for the brain and 60% for the liver up to 92 °C, while thermal diffusivity increased by 90% and 40%, respectively. However, the heat capacity did not significantly change in this temperature range. The thermal conductivity and thermal diffusivity were dramatically increased from 92 to 97 °C, which seems to be due to water vaporization and state transition in the tissues. Moreover, the measurement uncertainty, determined at each temperature, increased after 92 °C. In the temperature range of 22 to 45 °C, the thermal properties of pancreatic tissue did not change significantly, in accordance with the results for the brain and liver. For the three tissues, the best fit curves are provided with regression analysis based on measured data to predict the tissue thermal behavior. These curves describe the temperature dependency of tissue thermal properties in a temperature range relevant for hyperthermia and ablation treatments and may help in constructing more accurate models of bioheat transfer for optimization and pre-planning of thermal procedures.

Urticaria: recommendations from the Italian Society of Allergology, Asthma and Clinical Immunology and the Italian Society of Allergological, Occupational and Environmental Dermatology.

BACKGROUND: Urticaria is a disorder affecting skin and mucosal tissues characterized by the occurrence of wheals, angioedema or both, the latter defining the urticaria-angioedema syndrome. It is estimated that 12-22% of the general population has suffered at least one subtype of urticaria during life, but only a small percentage (estimated at 7.6-16%) has acute urticaria, because it is usually self-limited and resolves spontaneously without requiring medical attention. This makes likely that its incidence is underestimated. The epidemiological data currently available on chronic urticaria in many cases are deeply discordant and not univocal, but a recent Italian study, based on the consultation of a national registry, reports a prevalence of chronic spontaneous urticaria of 0.02% to 0.4% and an incidence of 0.1-1.5 cases/1000 inhabitants/year. METHODS: We reviewed the recent international guidelines about urticaria and we described a methodologic approach based on classification, pathophysiology, impact on quality of life, diagnosis and prognosis, differential diagnosis and management of all the types of urticaria. CONCLUSIONS: The aim of the present document from the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) is to provide updated information to all physicians involved in diagnosis and management of urticaria and angioedema.

Closed-Loop Temperature Control Based on Fiber Bragg Grating Sensors for Laser Ablation of Hepatic Tissue.

Laser ablation (LA) of cancer is a minimally invasive technique based on targeted heat release. Controlling tissue temperature during LA is crucial to achieve the desired therapeutic effect in the organs while preserving the healthy tissue around. Here, we report the design and implementation of a real-time monitoring system performing closed-loop temperature control, based on fiber Bragg grating (FBG) spatial measurements. Highly dense FBG arrays (1.19 mm length, 0.01 mm edge-to-edge distance) were inscribed in polyimide-coated fibers using the femtosecond point-by-point writing technology to obtain the spatial resolution needed for accurate reconstruction of high-gradient temperature profiles during LA. The zone control strategy was implemented such that the temperature in the laser-irradiated area was maintained at specific set values (43 and 55 °C), in correspondence to specific radii (2 and 6 mm) of the targeted zone. The developed control system was assessed in terms of measured temperature maps during an ex vivo liver LA. Results suggest that the temperature-feedback system provides several advantages, including controlling the margins of the ablated zone and keeping the maximum temperature below the critical values. Our strategy and resulting analysis go beyond the state-of-the-art LA regulation techniques, encouraging further investigation in the identification of the optimal control-loop.

Silicosis in finishing workers in quartz conglomerates processing.

INTRODUCTION: Outbreaks of silicosis have bene recently reported in artificial stone workers. AIM: To describe the features of silicosis in quartz conglomerate workers in North-Eastern Italy. METHODS: Active search of pneumoconiosis was performed in 11 companies of North-Eastern Italy involved in the fabrication of quartz conglomerate countertops. Occupational history, lung function tests, chest X-ray and high resolution computed tomography (HRCT) were performed. In selected cases, trans-bronchial biopsies were taken for histological evaluation and identification of silica crystals in the tissue. Cumulative exposure to crystalline silica was estimated. RESULTS: We recruited 45 workers and 24 cases of silicosis were diagnosed. Mean age at diagnosis was 43 years and duration of exposure to quartz conglomerate dust was 3.5 to 20 years. The average silica cumulative exposure was 4.3 mg/m3/y. Abnormal findings were detected in 42% of chest X-rays, in 33% of spirometry and 50% of carbon monoxide lung diffusion (DLco). HRCTs were abnormal in all cases showing well-defined rounded opacities, irregular/linear intralobular opacities and bilateral enlarged mediastinal lymph-nodes. Histological findings consistent with silicosis were observed in 24 cases. Numerous silica particles (diameter 0.1-5 µm) were identified in lung tissue. CONCLUSIONS: We reported an unexpected high incidence of silicosis in Italian workers exposed to quartz conglomerate dust. The results suggest that chest HRCT is indicated for screening of workers with high exposure to silica and DLco should be added to spirometry in health surveillance. More rigorous application of safety regulations and more effective preventive interventions at work are necessary.

Adalimumab Dose Tapering in Psoriasis: Predictive Factors for Maintenance of Complete Clearance.

Psoriasis can be managed successfully with long-term biologics. Real-life clinical practice may require dose tapering as a therapeutic option to reduce the risk of drug-exposure and to increase cost-effectiveness. The responsiveness to extended intervals between adalimumab doses and the possible predictive factors of maintenance of complete clearance were studied in a retrospective 7-year single-centre analysis. Thirty patients who achieved complete clearance with adalimumab underwent dose tapering, progressively extending between-dose intervals (to 21-28 days). Sixty percent of subjects (group A) maintained complete clearance, whereas 40.0% (group B) relapsed and were switched back to the standard dosage to re-achieve complete clearance. Body mass index (BMI) and time to achieve Psoriasis Area Severity Index (PASI-100) with adalimumab standard treatment before dose tapering were significantly lower in group A than in group B (multi-variate Cox regression: p < 0.05, Kaplan-Meier analysis: p < 0.001, respectively). This study suggests that patients with lower BMI and shorter time to achieve PASI-100 with adalimumab standard dose were significantly more likely to be candidates for dose tapering.