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OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of systemic pauci-immune necrotising vasculitides involving small vessels, characterised by the presence of specific ANCA autoantibodies directed to leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) and subdivided into three clinical entities: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The aetiology of AAV is unknown and many genetic, epigenetic and environmental factors have been reported to be involved in pathogenesis. Smoking is widely recognised as a risk factor for the development of many autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. This systematic review will analyse known data about the role of smoking in the development, clinical presentation and outcome of AAV. METHODS: Articles that examined interactions between tobacco smoking and AAV (GPA, MPA, EGPA) were included. All articles selected were in English. No limitation on publication date was established. Case reports were excluded. The systematic search was performed using PubMed/Medline and Cochrane Library databases. RESULTS: The search provided a total of 131 articles. Three studies were added, obtained from the review of the reference lists of articles. 70 were removed because they were duplicated or written in languages other than English. The title and abstract of 64 articles were screened. Of these, 30 were excluded as the title and/or abstract did not meet the inclusion criteria. Thus, 34 remained for full-text review, of which 8 were excluded. 26 articles were therefore included in this review. The role of smoking in AAV development is unclear. AAV patients current smoking appear appear to be younger and more frequently males, with a lower prevalence of EGPA and MPA than GPA. Ever smokers show higher relapse rate. Smoking seems to be associated with a higher risk of cardiovascular events during follow-up. Smokers incur an increased risk of infections. Finally, many data support smoking as a risk factor for end stage renal disease and mortality in AAV patients. CONCLUSIONS: Current data support the hypothesis that smoking influences prevalence, clinical phenotype and prognosis of ANCA-associated vasculitis. However, further studies are required to fully determine its role.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Fumar Tabaco , Humanos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Factores de Riesgo , Fumar Tabaco/efectos adversos , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Pronóstico , Poliangitis Microscópica/inmunología , Poliangitis Microscópica/epidemiología , Medición de Riesgo , Granulomatosis con Poliangitis/inmunología , Granulomatosis con Poliangitis/epidemiología , Granulomatosis con Poliangitis/etiología , Biomarcadores/sangreRESUMEN
Hyperinflammatory Coronavirus disease 2019 (COVID-19) and rapidly-progressive interstitial lung diseases (RP-ILD) secondary to inflammatory myopathies (IIM) present important similarities. These data support the use of anti-rheumatic drugs for the treatment of COVID-19. The aim of this study was to compare the efficacy of combining baricitinib and pulse steroids with the Standard of Care (SoC) for the treatment of critically ill COVID-19 patients. We retrospectively enrolled consecutive patients admitted to the Intensive Care Unit (ICU) with COVID-19-pneumonia. Patients treated with SoC (dexamethasone plus remdesivir) were compared to patients treated with baricitinib plus 6-methylprednisolone pulses (Rheuma-group). We enrolled 246 patients: 104/246 in the SoC and 142/246 in the Rheuma-group. All patients presented laboratory findings suggestive of hyperinflammatory response. Sixty-four patients (26.1%) died during ICU hospitalization. The mortality rate in the Rheuma-group was significantly lower than in the SoC-group (15.5 vs. 40.4%, p < 0.001). Compared to the SoC-group, patients in the Rheuma-group presented significantly lower inflammatory biomarker levels after one week of treatment. Higher ferritin levels after one week of treatment were strongly associated with mortality (p < 0.001). In this large real-life COVID-19 cohort, baricitinib and pulse steroids led to a significant reduction in mortality, paralleled by a prompt reduction in inflammatory biomarkers. Our experience supports the similarities between hyperinflammatory COVID-19 and the IIM-associated RP-ILD.
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Azetidinas , Tratamiento Farmacológico de COVID-19 , COVID-19 , Quimioterapia Combinada , Unidades de Cuidados Intensivos , Metilprednisolona , Purinas , Pirazoles , SARS-CoV-2 , Sulfonamidas , Humanos , Purinas/uso terapéutico , Purinas/administración & dosificación , Masculino , Femenino , Azetidinas/uso terapéutico , Azetidinas/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , COVID-19/mortalidad , COVID-19/complicaciones , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adenosina Monofosfato/administración & dosificación , Resultado del Tratamiento , Alanina/análogos & derivados , Alanina/uso terapéutico , Alanina/administración & dosificaciónRESUMEN
Amongst the range of bioprinting technologies currently available, bioprinting by material extrusion is gaining increasing popularity due to accessibility, low cost, and the absence of energy sources, such as lasers, which may significantly damage the cells. New applications of extrusion-based bioprinting are systematically emerging in the biomedical field in relation to tissue and organ fabrication. Extrusion-based bioprinting presents a series of specific challenges in relation to achievable resolutions, accuracy and speed. Resolution and accuracy in particular are of paramount importance for the realization of microstructures (for example, vascularization) within tissues and organs. Another major theme of research is cell survival and functional preservation, as extruded bioinks have cells subjected to considerable shear stresses as they travel through the extrusion apparatus. Here, an overview of the main available extrusion-based printing technologies and related families of bioprinting materials (bioinks) is provided. The main challenges related to achieving resolution and accuracy whilst assuring cell viability and function are discussed in relation to specific application contexts in the field of tissue and organ fabrication.
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Behçet's syndrome (BS) is a rare multisystem vasculitis involving blood vessels of any size. BS aetiology is still unclear to date, and the heterogeneity of clinical expression among ethnics and genders make early diagnosis challenging. However, so far, considerable efforts have been made toward the understanding of BS, leading researchers to agree that the coexistence of some environmental triggers and a genetical susceptibility both underlie BS aetiopathogenesis. In particular, viral agents, oral microbial flora, and mucosal microbiota have been widely explored in this regard, but still no specific microorganism has been definitely linked to the disease aetiology. Likewise, the concept that some environmental factors may play a role in BS clinical presentation has emerged based on the growing evidence that disease severity is usually higher in male patients, and that diet and fatigue may be involved in disease recurrence, especially in mucocutaneous manifestations. Moreover, smoke cessation is acknowledged as a risk factor for oral ulcerations, although the underlying mechanism is still not clear. All those environmental factors play their effects through epigenetic mechanisms. The aim of this review is to discuss the evidence on the role of environmental factors in BS aetiopathogenesis and clinical course.
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Food systems rely on natural resources for production causing their depletion. Sustainability assessment can encourage farms and agri-food companies to improve sustainability performances. Sustainability assessment frameworks and tools differ in their purposes, scope, methods of application, and required time for execution; however, most of them do not fit with value chains, or they do not cover all sustainability dimensions. Our objective is to propose a holistic framework to assess sustainability at agri-food value chains level. The proposed framework combines the Sustainability Assessment of Food and Agriculture systems (SAFA) (El Hage, 2012) [1] and The Agri-food Evaluation Framework (TEEB) [2]. It incorporates the concepts of Socio-Ecological Systems, Assemblage, and Social Practices. It integrates system dynamics by emphasising human and natural capital stocks and their users. We explain in detail the methodological steps we followed to construct and to apply this new framework to two case studies in Italy and France. The new framework was applied to real-life case studies and has shown its effectiveness and demonstrates its potential for widespread use in similar scenarios.
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Background: Maternal phenylketonuria (mPKU) is a pathologic condition occurring in the fetus of a mother with PKU that is caused by prolonged elevated intrauterine blood phenylalanine (Phe) levels, which can lead to congenital abnormalities and mental retardation of newborns. Management of PKU during pregnancy can be challenging as protein substitutes may exacerbate nausea, vomiting, and gastrointestinal symptoms. Aim: To report the successful management of four PKU pregnant women. Methods: The patients were administered with prolonged-release amino acid supplementation and were recommended to follow a strict diet. Blood Phe concentration, adherence to diet, and occurrence of adverse events were monitored. Results: All patients achieved safe levels of blood Phe concentration (120-360 µmol/L) since preconception and during pregnancy (mean Phe concentration values of 143.34 ± 137.59, 226.48 ± 194.57, 186.68 ± 133.67, and 187.47 ± 42.59 µmol/L). During the first trimester of pregnancy, all patients manifested gastrointestinal symptoms such as nausea, gastrointestinal reflux, and abdominal bloating, which were managed by either changing protein substitute or extending the time window between different meals and amino acid mixtures administration. The four women continued their pregnancies without experiencing further complications and delivered neonates with normal growth parameters and no malformations. Conclusion: Findings of this case series suggest that the intake of a prolonged-release amino acid mixture in granules is well tolerated by pregnant PKU patients, eventually leading to good metabolic control and fetal growth within normal ranges.
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Systemic vasculitides comprise a collection of rare and heterogeneous disorders capable of impacting any organ and system, posing a considerable burden of mortality and comorbidity. As with previous annual reviews of this series, this review will offer a critical overview of the latest literature on pathogenesis, biomarkers, and treatment options in both small- and large-vessel vasculitis.
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Biomarcadores , Vasculitis Sistémica , Humanos , Vasculitis Sistémica/terapia , Vasculitis Sistémica/inmunología , Vasculitis Sistémica/diagnóstico , Vasculitis Sistémica/epidemiología , Biomarcadores/sangre , Resultado del Tratamiento , Inmunosupresores/uso terapéutico , Factores de RiesgoRESUMEN
PURPOSE OF REVIEW: Cryoglobulinemic vasculitis (CV) is an immune complex mediated small vessel vasculitis characterized by the presence of cryoglobulins in serum, often associated with hepatitis C infection, systemic autoimmune diseases or hematological conditions. The focus of this review is to provide an update on new insights into pathogenesis, epidemiology and therapies of infectious and noninfectious type II and type III CV. RECENT FINDINGS: The introduction of new antiviral drugs for treatment of hepatitis C infection implied major changes in HCV-related CV, allowing to shed new lights on CV pathogenesis and mechanisms of relapse and, therefore, to increase the relevance of autoimmune diseases in CV epidemiology. Specific B-cell clones are involved in the production of pathogenic immune complexes that leads to small-vessel vasculitis. Therefore, both antiviral treatments [direct-acting antivirals (DAAs) and oral nucleot(s)ide analogues] and targeted anti-CD20 therapies (rituximab) prove to be safe and effective options, leading to a better prognosis. Association of Sjögren syndrome and CV defines a specific phenotype of patients, characterized by severe manifestations and poor outcome. SUMMARY: Removing viral stimulation on B-cells through direct-acting antivirals and blocking B-cells proliferation and differentiation with rituximab are the goals of treatment of CV. However, further research is needed to identify prognostic factors of refractory and relapsing disease.
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Crioglobulinemia , Hepatitis C Crónica , Hepatitis C , Vasculitis , Humanos , Rituximab/uso terapéutico , Antivirales/uso terapéutico , Hepatitis C Crónica/complicaciones , Hepatitis C/complicaciones , Vasculitis/tratamiento farmacológico , Vasculitis/etiología , Crioglobulinemia/etiología , Crioglobulinemia/complicaciones , HepacivirusRESUMEN
Fused filament fabrication (FFF) is an additive manufacturing process where a thermoplastic polymeric material, provided in the form of a filament, is extruded to create layers. Achieving a consistent flow of the extruded material is key to ensure quality of the final part. Extrudate flow depends on many factors; among these, the rate at which the filament is fed into the extruder. In a conventional FFF machine, filament transport is achieved through the use of a drive gear. However, slippage between the gear and the filament may occur, leading to reduced transport and the consequent local decrease of extrudate flow rate, which in turn leads to a series of imperfections in the fabricated part due to underextrusion, including reduced density. In this work, we propose a closed-loop control system to ensure the correct filament transport to the extruder. The system works through the comparison between the nominal transport of the filament and the actual filament transport measured using an encoder. The measured value is used to correct the filament feed rate in real time, ensuring a material flow close to the nominal one, regardless of the other process parameters. In this work, an instrumented FFF machine prototype was used to investigate the performance of the approach. For validation, parts were realized using different process parameters, while enabling and disabling the closed-loop control system. Results showed that the relative filament transport error decreased from up to 9% to below 0.25% and a density increase up to â¼10% regardless of the process parameters, as well as the reduction of interlayer and intralayer voids, as highlighted through cross-sectional imaging of realized samples. A reduction of defects on realized parts was observed, especially at higher fabrication feed rates.
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BACKGROUND: Telemedicine enables patients to receive better care via the simplification of procedures while allowing for a significant reduction of in-office appointments and emergency room visits. The "Cardiologia in linea" project started with the objective of strengthening communications between cardiologists and primary care, particularly with general practitioners. METHODS: Between January 2017 and October 2022, by means of a facilitated telephonic and digital contact between territorial professionals and the cardiologist, the project provided in most cases immediate answers to cardiology queries, which were logged. RESULTS: A total of 2066 telephonic or digital consultations have been recorded, originating from 316 general practitioners in the Trento province (Italy). The mean age of patients was 76.4 years, 53% were male. After consultation, an immediate response was provided in 1989 (96%) of cases. A total of 1112 (54%) cardiology visits were avoided. After the consultation, a cardiologic visit was suggested in 29 cases (1%), and the emergency system was activated in 20 cases (1%). Overall, most questions concerned direct oral anticoagulant prescriptions (537 cases, 31%) and anti-hypertensive treatment (241 cases, 14%). CONCLUSIONS: The "Cardiologia in linea" project demonstrated a low-cost improvement in the patient assistance workflow, in the communication between hospital cardiology and primary care, while reducing the number of emergency room accesses. The project successfully shows the feasibility of a real-time dialogue between the general practitioner and the hospital cardiologist.
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Cardiólogos , Consulta Remota , Humanos , Masculino , Anciano , Femenino , Consulta Remota/métodos , Derivación y Consulta , Hospitales , Italia , Atención Primaria de Salud/métodosRESUMEN
Systemic vasculitides are heterogeneous disabling diseases characterised by chronic inflammation of the blood vessels potentially leading to tissue destruction and organ failure. The recent COVID-19 pandemic has had a significant impact on the epidemiology and management of patients with systemic vasculitis. In parallel, new insights have been provided on systemic vasculitis pathogenetic mechanisms, possible new therapeutic targets, and newer glucocorticoid-sparing treatments with better safety profiles. As in the previous annual reviews of this series, in this review we will provide a critical digest of the most recent literature regarding pathophysiology, clinical manifestations, diagnostic tools and treatment options in small- and large-vessel vasculitis focusing on precision medicine in vasculitis.
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COVID-19 , Vasculitis Sistémica , Vasculitis , Humanos , Pandemias , Vasculitis Sistémica/diagnóstico , Vasculitis Sistémica/tratamiento farmacológico , Vasculitis Sistémica/epidemiología , Vasculitis/diagnóstico , Vasculitis/tratamiento farmacológico , Vasculitis/epidemiología , InflamaciónRESUMEN
The guidelines for the management of patients affected by propionic acidemia (PA) recommend standard cardiac therapy in the presence of cardiac complications. A recent revision questioned the impact of high doses of coenzyme Q10 on cardiac function in patients with cardiomyopathy (CM). Liver transplantation is a therapeutic option for several patients since it may stabilize or reverse CM. Both the patients waiting for liver transplantation and, even more, the ones not eligible for transplant programs urgently need therapies to improve cardiac function. To this aim, the identification of the pathogenetic mechanisms represents a key point. Aims: This review summarizes: (1) the current knowledge of the pathogenetic mechanisms underlying cardiac complications in PA and (2) the available and potential pharmacological options for the prevention or the treatment of cardiac complications in PA. To select articles, we searched the electronic database PubMed using the Mesh terms "propionic acidemia" OR "propionate" AND "cardiomyopathy" OR "Long QT syndrome". We selected 77 studies, enlightening 12 potential disease-specific or non-disease-specific pathogenetic mechanisms, namely: impaired substrate delivery to TCA cycle and TCA dysfunction, secondary mitochondrial electron transport chain dysfunction and oxidative stress, coenzyme Q10 deficiency, metabolic reprogramming, carnitine deficiency, cardiac excitation-contraction coupling alteration, genetics, epigenetics, microRNAs, micronutrients deficiencies, renin-angiotensin-aldosterone system activation, and increased sympathetic activation. We provide a critical discussion of the related therapeutic options. Current literature supports the involvement of multiple cellular pathways in cardiac complications of PA, indicating the growing complexity of their pathophysiology. Elucidating the mechanisms responsible for such abnormalities is essential to identify therapeutic strategies going beyond the correction of the enzymatic defect rather than engaging the dysregulated mechanisms. Although these approaches are not expected to be resolutive, they may improve the quality of life and slow the disease progression. Available pharmacological options are limited and tested in small cohorts. Indeed, a multicenter approach is mandatory to strengthen the efficacy of therapeutic options.
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PURPOSE OF REVIEW: To provide an overview of existing literature on pathogenetic and clinical aspects of cardiac and vascular involvement in eosinophilic granulomatosis with polyangiitis (EGPA). RECENT FINDINGS: In EGPA, cardiac and vascular involvement are more common than previously thought. However, no international recommendations on the topic are available yet. Herein, we summarize the existing evidence on the topic and propose a diagnostic approach for cardiac involvement in EGPA. The prevalence of cardiovascular involvement in patients with EGPA varies greatly among published studies, ranging between 3.1-18.7% for occlusive arterial disease, 5.8-30% for venous thrombosis and 17-92% for heart involvement. Cardiac involvement in EGPA is associated with high mortality even though manifestations are heterogeneous. In principle, every anatomical structure of the heart can be involved, and EGPA-related heart disease may be completely asymptomatic at first. A careful diagnostic work-up for early detection and prompt treatment initiation is therefore required. While cardiac manifestations are more common in anti-neutrophil cytoplasmic antibodies (ANCA)-negative patients, arterial and venous thrombotic events are not linked to ANCA status but correlate closely with disease activity and accumulate at disease onset. Thrombotic events (mainly venous) are considerably more frequent in EGPA than in the general population contributing substantially to morbidity and highlighting the importance of developing specific prevention strategies for patients who are diagnosed with EGPA.
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Síndrome de Churg-Strauss , Granulomatosis con Poliangitis , Cardiopatías , Anticuerpos Anticitoplasma de Neutrófilos , Síndrome de Churg-Strauss/complicaciones , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/tratamiento farmacológico , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/tratamiento farmacológico , Corazón , HumanosRESUMEN
AIMS: Telemedicine may be of benefit in patients with heart failure (HF), although virtual visits are often carried out on an ad hoc basis. Herein, we discuss a structured protocol that defines all the steps needed for virtual visits, LEAP Virtual Visit, which includes guides and support kits for clinicians and patients. METHODS: A working group of clinicians was established to develop a protocol for virtual visits. The virtual model for monitoring HF patients was based on measurement and sizing of patient flows, type of services, and critical organizational points. The process of virtual visits was broken down to identify the specific activities, players, roles, and support tools needed for implementation in daily practice. RESULTS: In the protocol developed, sections were included on patient eligibility, exams, supportive tools, and practical organizational aspects. IT requirements were also considered and the most widely used teleconference platforms were compared according to features that were considered to be priority for virtual visits. Protocols and support kits were developed, including guides for clinicians and patients, two questionnaires to assess the level of satisfaction, patient diary, disease awareness brochure, and template to monitor key performance indicators. The phases include an enrolment phase, document sharing phase, pre-evaluation phase, the virtual visit itself, and the post-visit phase. The protocol for the virtual visit was divided into 8 sequential steps to be carried out between the clinic and patient/caregiver. CONCLUSION: The protocol described can be expected to have a number of benefits for the patient, clinic, and healthcare structure.
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Insuficiencia Cardíaca , Telemedicina , Instituciones de Atención Ambulatoria , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Humanos , Encuestas y Cuestionarios , Telemedicina/métodosRESUMEN
Systemic vasculitis are rare heterogeneous disorders potentially involving any organ and system with a relevant burden of mortality and comorbidity.As in the previous annual reviews of this series, in this review we will provide a critical digest of the most recent literature regarding pathophysiology, clinical manifestations, diagnostic tools and treatment options in small- and large-vessel vasculitis.
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Vasculitis Sistémica , Humanos , Vasculitis Sistémica/diagnóstico , Vasculitis Sistémica/terapiaRESUMEN
The fused filament fabrication (FFF) process is widely used for producing prototypes and functional parts for diverse applications. While FFF is particularly attractive due to its cost-effectiveness, on the other hand, the fabricated parts have limitations in terms of large manufacturing time and reduced mechanical properties. The latter is strongly influenced by the fabrication process parameters, which affect the interlayer bonding and the adhesion between consecutive layers. Several works presented in the literature analysed the correlation between mechanical properties and process parameters. It was demonstrated that an increase in the fabrication feed rate causes slippage between filament and the feeding system, which leads to a decrease in the extruded material flow, and thus in part density. This work aims to investigate how the limitation of the slippage phenomenon affects the mechanical properties of parts fabricated using the FFF process. A prototype machine, equipped with a closed-loop control system on filament transport, was used to fabricate samples for tensile tests and dynamical mechanical analysis. Samples fabricated enabling the filament transport control showed an increase both in ultimate tensile strength and elongation at break for those fabricated with disabled control, whilst a decrease in stiffness was observed. In addition, the results showed that the use of a filament transport control system on a FFF machine increases the possibility of fabricating high value-added parts.
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OBJECTIVES: In patients with systemic autoimmune rheumatic disorders (SARDs), vaccination with SARS-CoV-2 mRNA vaccines has been proposed. The aim of this study is to evaluate the immune response elicited by vaccination with mRNA vaccine, testing IgM, IgA and IgG antibodies to SARS-CoV-2 receptor-binding domain (RBD) and measuring neutralising antibodies. METHODS: IgG, IgM and IgA anti-RBD antibodies were measured in 101 patients with SARDs. Antibodies inhibiting the interaction between RBD and ACE2 were evaluated. Antibody avidity was tested in a chaotropic ELISA using urea. Twenty-one healthcare workers vaccinated with mRNA vaccine served as control group. RESULTS: Anti-RBD IgG and IgA were produced after the first dose (69% and 64% of the patients) and after the boost (93% and 83%). Antibodies inhibiting the interaction of RBD with ACE2 were detectable in 40% of the patients after the first dose and 87% after boost, compared with 100% in healthy controls (p<0.01). Abatacept and mycophenolate had an impact on the titre of IgG anti-RBD antibodies (p<0.05 and p<0.005, respectively) and on the amount of neutralising antibodies. No effect of other therapies was observed. Vaccinated patients produce high avidity antibodies, as healthy controls. CONCLUSIONS: These data show that double-dose vaccination induced in patients with SARDs anti-RBD IgG and IgA antibodies in amounts not significantly different from controls, and, most interestingly, characterised by high avidity and endowed with neutralising activity.
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Enfermedades Autoinmunes , COVID-19 , Anticuerpos Antivirales , Humanos , SARS-CoV-2 , Vacunas Sintéticas , Vacunas de ARNmRESUMEN
PURPOSE: Italian expenditure for vitamin D greatly increased in the last few years, reaching 314 million ($376.8 million) in 2019. In Italy, the main cause of the increase in public spending for vitamin D is the marketing of high-cost medicines. At national and regional levels, some interventions have been performed to reduce expenditure, but spending has continued to increase. The aim of this work is to propose a new saving strategy determined by an analysis of a significant sample of the market. METHODS: Data on the use of vitamin D formulations, including data for the different active substances that represent its pharmaceutical analogue and composition of groups of equivalence, were extrapolated from the Italian Medicines Agency transparency lists and from the Farmadati database. Data on pharmaceutical expenditure were obtained from the Data Warehouse of Liguria Region; the composition of this expenditure was analyzed in detail, focusing on the characteristics of the pharmaceutical preparations and their cost (price per defined daily dose). FINDINGS: Vitamin D expenditure paralleled that of cholecalciferol, the most used active ingredient, which in Liguria increased from 643,352 ($772,022.4) in 2010 to 8,006,574 ($9,607,888.8) in 2019 (increase of 1144%). Spending focused on high-cost formulations, exceeding 90% of total cholecalciferol cost in 2019. We simulated a possible optimization of the expense for cholecalciferol by applying a revised price to all the cholecalciferol consumptions in high-cost products because these formulations do not have an added therapeutic value, finding that the saving would be at least 60%. National data on the detailed expenditure composition for vitamin D are not available, but we found a strong resemblance between total cholecalciferol expenditure time series in Italy and the Liguria Region. IMPLICATIONS: The expense of cholecalciferol and consequently the expense of vitamin D could be optimized by modifying the reimbursement of high-cost formulations. At a national level, savings should be proportional to that estimated for the Liguria Region. On the basis of the 2019 data, Italian savings with respect to total cholecalciferol expenditure should be 170.65 million ($204.78 million); per capita cholecalciferol expenditure would shift from 4.66 ($5.59) to 1.84 ($2.21).