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Amyloidosis is a heterogenous group of disorders, caused by the deposition of insoluble fibrils derived from misfolded proteins in the extracellular space of various organs. These proteins have an unstable structure that causes them to misfold, aggregate, and deposit as amyloid fibrils with the pathognomonic histologic property of green birefringence when viewed under cross-polarized light after staining with Congo red. Amyloid fibrils are insoluble and degradation-resistant; resistance to catabolism results in progressive tissue amyloid accumulation. The outcome of this process is organ disfunction independently from the type of deposited protein, however there can be organ that are specifically targeted from certain proteins., Competing Interests: Disclosure No conflicts of interest to declare for any author in relation to the submitted work. Outside the submitted work: G. Sinagra received personal fees for occasional educational activities from Biotronik, Boston Scientific, Astra Zeneca and Novartis; M. Merlo received congress fees from Novartis, Vifor Pharma, Astra Zeneca and Novo Nordisk and research grant and congress fees from Pfizer, without any control on intellectual contents., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Foot ulcers have a relevant economic impact on Health Care Systems and the cost-effectivenesseffectiveness of options is not clear. The aim of this study was the assessment of costs for ulcers treatment after 6, 12, and 18 months of follow-up, compared to those for major amputation. Methods: A retrospective study was carried out on 196 types 2 diabetic patients with foot ulcers. The principal endpoints were 1) the proportion of recovered patients among those with ulcers not healed after 6 and 12 months; 2) the assessment of direct costs for treatment of ulcers 6, 12, and 18 months of follow-up, as compared to the cost of major amputation. The economic evaluation was performed considering the perspective of the local health system. Results: Out of 196 patients, 85(46.2%), 131(71.6%), and 140(85.9%) healed within 6, 12, and 18 months, respectively. The average health cost during the 18-month follow-up was 5402€ per patient. We calculated hypothetical costs for three different scenarios, in which patients who did not heal within 6 months underwent a major amputation at 6, 1,2, or 18 months. Costs for the standard of care for all these scenarios (6,094, 7,256, and 7649€ for 6, 12, or 18 months, respectively) were significantly lower than that for major amputations (21,065€). Conclusions: A conservative approach appears more convenient than major amputations in ulcers not healing after 6 months, irrespective of the estimated risk of individual patients.

Background: Alternaria alternata (AA) sensitisation is a common cause of respiratory allergies such as rhinitis and asthma. So far there are no controlled double-blind trials evaluating the efficacy and safety of specific sublingual immunotherapy (SLIT) in AA allergies., Objective: To evaluate the efficacy of SLIT treatment in terms of clinical improvement and rescue medication usage in patients with confirmed AA respiratory allergy., Subjects and Methods: A randomised, parallel group study in 52 subjects was conducted (32 men, mean age 20 ± 9 years) with clinically- and laboratory-confirmed AA respiratory allergies (allergic rhinitis with or without mild-to-moderate asthma). Patients were randomly assigned to SLIT treatment (SLITone Alternaria, ALK-Abellò, Denmark) one vial per day without up-dosing for 3 consecutive years (n = 34) or to a control group (n = 18) with a random allocation ratio of 2:1. Clinical improvement was assessed by evaluating patient-reported outcome (PRO) using a 6 cm visual analogue scale (0: extreme worsening; 3: no change; 6: extreme improvement). The VAS score was evaluated every year with an intra- and inter-group comparison. Rescue medication score (MS) was assessed by evaluating symptomatic drug consumption., Results: After 3 years the VAS score was 4.7 ± 0.8 in the SLIT group and 2 ± 1.6 in the control group (p = 0.0002). Clinical improvement was observed in 33 out of 34 subjects in the SLIT group (97%) and in 5 out of 18 in the control group (27%) (p = 0.0001; Fisher's exact test). The MS significantly (p = 0.0001) decreased in the SLIT group from 4.3 to 1.7 at the end of 3 years' treatment. In the control group MS increased from 3.4 to 4.0 by the end of the trial. No serious adverse events were observed in the either group. Six patients in the SLIT group (17%) reported side-effects, in general mild and transient. One patient prematurely discontinued the treatment due to gastrointestinal discomfort., Conclusion: The current study has shown that a 3-year course of SLIT is efficacious and well-tolerated in subjects with AA respiratory allergies.

Background: Although several studies support the efficacy of specific immunotherapy in allergic asthma, its benefit compared with that of standardized pharmacologic intervention remains unknown., Objective: A double-blind, placebo-controlled trial in 72 patients with mild-to-moderate asthma and allergy to house dust mite (HDM; Dermatophagoides species) was conducted to assess the effects of specific immunotherapy added to guideline-adjusted pharmacologic treatment and allergen avoidance., Methods: After 1 observational year of pharmacologic treatment and standard measures of HDM avoidance, 2 groups of asthmatic subjects were randomly assigned to receive specific immunotherapy consisting of subcutaneous injections of either a mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae vaccine (n=41) or placebo (n=31) for 3 years. Medications were adjusted every 3 months according to the Global Initiative for Asthma guidelines., Results: The adjustment of treatment was associated with a reduction in asthma symptom scores in all subjects. The addition of specific immunotherapy was associated with a decrease in the number of subjects requiring rescue bronchodilators, an increase in morning and evening peak expiratory flow, and a reduced skin sensitivity to HDM extracts. The addition of specific immunotherapy had no significant effects on the cumulative dose of inhaled corticosteroids, asthma symptoms, lung volumes, or bronchial responsiveness to methacholine., Conclusion: These results suggest that specific immunotherapy added to pharmacologic treatment and HDM avoidance provides marginal but statistically significant clinical benefits, possibly by reducing the allergic response of asthmatic patients sensitized to HDM.

Epidemiological studies on the pollens responsible for allergic diseases throughout Italy are lacking. Routine diagnostic panels consist prevalently of grass, Parietaria, weeds, birch, olive and mugwort. Considering the great variety of Italian geographical areas and the observation of the growing allergological importance of new botanical species (e.g., ambrosia), a survey on pollen species considered "minor" was necessary. A panel of "emerging" pollens (birch, hazelnut, alder, hornbeam, cypress, ragweed) and a routine panel were used to skin prick test 2,934 consecutive outpatients with respiratory pathology of suspected allergic origin, in 21 centers across Italy. A specific questionnaire was compiled. It was found that 20.1% of patients did not react to allergens tested, 28.2% were positive for at least one emerging pollen and 51.7% did not react to emerging pollens but tested positive for at least one allergen from the routine panel. The prevalence of single pollen species was related to geographical areas. Ragweed pollen was shown to provoke asthma much more frequently than other pollens. Hitherto scarcely considered pollens play a considerable role in causing allergic diseases in Italy. In the great majority of patients, positivity for these pollens was associated with positivity to the better recognized group of pollen allergens, although in some cases they were the primary pathogenic agent. We suggest that these more recently considered allergens be included in routine diagnostic panels.

Background: sensitization to fungi spores is often associated with sensitization to other allergens and so it is difficult to estabilish the exact cause of illness., Objective: the aim of the study was to evaluate a group of patients monosensitized to Alternaria and to establish the prevalence, periodicity and clinical profile of this kind of sensitization., Methods: 37 subjects who were monosensitized to Alternaria (prick-test positive), according to a previous epidemiological study were evaluated. Clinical symptoms and the period of their occurrence were taken into consideration as well as immunological parameters (RAST)., Results: 20 patients (over 50%) included in the study proved to be affected by asthma associated with other allergic symptoms and 22 patients (60%) presented perennial symptoms. The RAST carried out on 34 monosensitized subjects proved positive in 11 and negative in 23., Conclusions: Alternaria sensitization is characterized by a perennial periodicity with severe respiratory symptoms (asthma) which occur primarily in children. Prick test is preferable to and more reliable than RAST as a diagnostic test.

Background: The actual prevalence of sensitization to Alternaria is not known, partly due to the unreliability of diagnostic extracts., Objective: To assess skin positivity to extracts of Alternaria in a wide population of Italian patients suffering from respiratory symptoms using a biologically standardized extract., Methods: A total of 2942 patients were skin prick tested with Alternaria, and a panel of common inhalant allergens. Blood samples for specific IgE quantitation were taken both from patients positive and from patients negative (control group) to Alternaria extract., Results: Three hundred six patients (10.4%, ranging from 1.8% in Turin to 29.3% in Cagliari) were positive to Alternaria; 37 were sensitized to only this mold, while the remaining 269 were sensitized to at least one other allergen. Of the Alternaria-positive patients, 79.7% suffered from rhinitis and 53.3% from asthma, either alone or associated with other symptoms., Conclusions: We suggest that, at least in Italy and in countries with similar climatic and environmental situations, standardized Alternaria extract should be included in the panel commonly used in investigating the allergen responsible in patients suffering from respiratory allergy.

Little knowledge is available on molds either from the environmental or clinical points of view. The latter is mainly due to the lack, until recent times, of purified and standardized extracts. Injective immunotherapy, largely used for patients allergic to mites and pollens, is regarded with some concern for molds. On the other hand, mold-related allergic symptoms (i.e.,from Alternaria tenuis) have in Italy an incidence of about 5 percent, mainly in young patients. We have therefore run a pilot study comparing the efficacy and safety of injective (SIT) and sublingual (SLIT) immunotherapy by administering the same purified and standardized extract of Alternaria tenuis to a total of 23 patients for two years, according to an open experimental plan. Excellent tolerance was shown to SLIT while four (two medium-grade) side effects appeared with SIT. Clinical improvement, subjectively stated comparing symptoms (mainly rhinitis) and drug consumption before and after the therapy, confirmed by an increase in the Specific Nasal Provocation threshold, was obtained with both therapies, but with a statistically significant difference in favour of SLIT. Skin reactivity and blood Alternaria tenuis specific IgE, total IgG and IgG changed in the SIT-treated group, while no statistically significant change was shown in the SLIT-treated group. These results are in good agreement with previous reports on SIT and SLIT with other inhalant allergens (mites, grasses), and suggest the potential use of SLIT for Alternaria allergy, mainly in young patients, when there are concerns about the safety of and compliance with the traditional injective therapy.

The Authors review the use of provocation test, added to other diagnostic procedures, in the study of extrinsic allergic alveolitis (E.A.A.). In the light of the still present uncertainty on the pathogenesis of the disease and on the ethics of these tests, the Authors assert that the provocation tests in E.A.A. are inadvisable because on the one hand they are uncertain as regards execution and evaluation and on the other hand they are dangerous for the patient.

We investigated the intensity and duration of the effect of a single dose of slow-release theophylline on bronchial hyperresponsiveness to ultrasonically nebulized distilled water in asthma. In six subjects with a history of mild asthma, we measured airway responsiveness to ultrasonically nebulized distilled water and serum theophylline at 4, 8, and 12 hours after treatment with placebo or slow-release theophylline (10 +/- 1 mg/kg, orally). To assess bronchial responsiveness, dose-response curves were established by plotting the baseline value of FEV1 and the largest FEV1 after each doubling dose of nebulized distilled water against the dose of nebulized water. The degree of bronchoconstriction induced by ultrasonically nebulized distilled water was significantly inhibited at 4, 8, and 12 hours after treatment with theophylline, at serum levels of 14.8 +/- 4.6, 14.4 +/- 2.8, and 12.0 +/- 2.5 micrograms/mL theophylline (mean +/- SD). Tremor occurred in three patients and was associated with nausea, epigastric pain, and tachycardia in one of them. We conclude that a single dose of slow-release theophylline has a prolonged protective effect on bronchoconstriction induced by ultrasonically nebulized distilled water, but in some subjects is associated with side effects that limit its clinical usefulness.

Mitochondria incubated aerobically in the presence of tetrapropylammonium and weak acids and in the presence of trace amounts of tetraphenylboron undergo a series of damped oscillations reflecting cycles of osmotic swelling and shrinkage. The matrix volume changes are consequent to transport of tetrapropylammonium catalytically stimulated by tetraphenylboron. The amplitude and frequency of the oscillations increase with the concentration of tetrapropylammonium, as required for critical rates and extents of ion influx. Addition of bovine serum albumin abolishes both the uptake of tetrapropylammonium and the oscillations. Volume oscillations are paralleled by cyclic activation and depression of the respiratory rate. Two lines of evidence suggest that the train of damped oscillations depends on the cyclic activation of an electroneutral exchange of H+ with organic cations rather than on cyclic uncoupling. First, further increase of cation permeability due to a pulse of tetraphenylboron, after initiation of cation efflux, restores cation influx. Second, addition of Mg2+, which abolishes the oscillations, has a much more marked inhibitory effect on the process of cation efflux than on cation influx. Conversely, addition of A23187, which removes membrane-bound Mg2+, promotes cation efflux and thus the oscillations. It is suggested that, in the present system, stretching of the inner membrane and Mg2+ depletion result in activation of an electroneutral H+/organic cation exchange, and that cyclic activation of this reaction results in damped oscillations.

An account is given of the model employed for the provision of psychological care over the last 9 years at the Microcythemia Centre, Department of Paediatrics, University of Turin, by a team composed of paediatricians and child neuropsychiatrists. Reference is made to a series of 280 patients aged 0-25 years. The psychodynamic is adopted and provision is made for individual and group meetings with young and adolescent patients and their parents that are held as part of the Centre's ordinary activities. This procedure has made it possible to understand and face up to the psychological implications of thalassaemia and its treatment and has considerably improved both compliance and the quality of life. Stress is laid on the importance of a good rapport between patients and the Centre. This can be obtained through continuous collaboration between physicians and psychiatrists and or psychologists with a psychodynamic background.